Clinical Trials Mesothelioma

Mesothelioma Clinical Trials 2026
April 2026 Trial Landscape
Recruiting Worldwide	93 trials
Recruiting in U.S.	52 trials
FDA-Approved Regimens	3 systemic
Phase I Trials	23
Phase I/II Trials	15
Phase II Trials	19
Phase III Recruiting	2 + VT3989 opening H1 2026
Patient Participation	Only 8%
New U.S. Cases/Year	~3,000
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Mesothelioma clinical trials are research studies that evaluate new treatments, drug combinations, and therapeutic approaches for patients diagnosed with malignant mesothelioma. As of April 2026, ninety-three mesothelioma clinical trials are actively recruiting patients worldwide, with fifty-two enrolling in the United States, spanning immunotherapy, targeted therapy, CAR-T cell therapy, radiation, device-based treatment, and surgical combinations. Despite this unprecedented breadth of options, patient participation remains critically low at just 8%, meaning hundreds of open treatment slots go unfilled each year.

Three systemic therapy regimens are now FDA-approved for malignant pleural mesothelioma: cisplatin plus pemetrexed (approved 2004), nivolumab plus ipilimumab (approved October 2020), and pembrolizumab plus pemetrexed plus platinum chemotherapy (approved September 17, 2024). The most significant recent milestone is the CheckMate 743 five-year update, published in the Journal of Clinical Oncology in February 2026, confirming that nivolumab plus ipilimumab achieves a 14% five-year overall survival rate versus 6% with chemotherapy (HR 0.74, 95% CI 0.62-0.88). In non-epithelioid disease, the five-year survival gap was even more dramatic: 12% versus 1% (HR 0.48), representing one of the most significant survival benefits reported in this historically treatment-resistant subgroup.

Mesothelioma clinical trials at a glance:

• 93 trials recruiting worldwide with only 8% patient participation — hundreds of available treatment slots go unfilled each year despite proven survival benefits from investigational therapies
• VT3989 TEAD inhibitor advancing to Phase III in H1 2026 — the sole surviving TEAD inhibitor achieved 32% objective response rate and 86% disease control rate in 22 patients at the optimized dose, with a Phase III registrational trial opening as the first-ever pivotal trial for a targeted therapy in mesothelioma
• Pembrolizumab plus chemotherapy FDA-approved September 2024 — KEYNOTE-483 demonstrated 52% objective response rate versus 29% with chemotherapy alone (p<0.00001) and a significant survival advantage for non-epithelioid patients (HR 0.57)
• CheckMate 743 five-year data confirm durable immunotherapy benefit — 14% versus 6% five-year overall survival; 17% of responders still in response at five years versus 0% in the chemotherapy arm
• CAR-T cell therapy achieves 83% one-year survival — Memorial Sloan Kettering's intrapleural CAR-T program demonstrated unprecedented durability in mesothelioma, with cells persisting over 100 days in 39% of patients
• BNT327/PM8002 bispecific antibody achieves 51.6% overall response — this PD-L1/VEGF-A bispecific antibody demonstrated exceptional results including 75% response rate in peritoneal mesothelioma patients (8 patients, 100% disease control rate), with a Phase III trial registered July 2025
• ATOMIC-Meso pegargiminase BLA under FDA review — this first-in-class arginine depletion therapy quadrupled three-year survival versus placebo in non-epithelioid mesothelioma patients; an FDA decision is expected late 2026 or early 2027
• UV1 telomerase vaccine granted FDA Fast Track — the NIPU trial demonstrated 31% versus 16% overall response rate and 15.4 versus approximately 11 months median overall survival when UV1 was added to nivolumab plus ipilimumab, earning FDA Fast Track designation in February 2024
• ISM6331 AI-designed drug enters human testing — Insilico Medicine's pan-TEAD inhibitor reached first-in-human dosing in January 2025 after being designed using artificial intelligence in under five years, compared to the typical ten to fifteen year drug development timeline
• NCI CAR-T trial is free to patients — the TNhYP218 trial at the NIH Clinical Center in Bethesda, Maryland provides all medical care at no cost to participants, with some travel expenses covered
• New U.S. cases remain steady at approximately 3,000 per year — mesothelioma continues to be diagnosed decades after asbestos exposure, with a median latency period of 30 to 50 years

Trial / Metric	Key Finding	Status (April 2026)
Active Recruiting Trials	93 worldwide (52 U.S.); Phase I: 23, Phase I/II: 15, Phase II: 19, Phase III: 2 recruiting + VT3989 opening H1 2026	Current
eVOLVE-Meso Phase III (NCT06097728)	825-patient enrollment target; AstraZeneca volrustomig (PD-1/CTLA-4 bispecific) + chemotherapy vs. investigator's choice; first-line unresectable pleural mesothelioma	Recruiting globally
VT3989 TEAD Inhibitor	32% ORR, 86% DCR, 10-month mPFS at 100 mg 2-on/2-off dose (n=22); Orphan Drug + Fast Track designations; potential approval 2028-2029	Phase III opening H1 2026
CheckMate 743 Five-Year Update	Nivolumab + ipilimumab: 14% vs. 6% five-year OS; non-epithelioid 12% vs. 1% (HR 0.48); 17% of responders ongoing at 5 years	Published Feb 2026
KEYNOTE-483 (Pembrolizumab + Chemo)	17.3 vs. 16.1 months median OS (HR 0.79); 52% vs. 29% ORR; non-epithelioid HR 0.57; FDA approved September 2024	FDA-approved
MSK Intrapleural CAR-T (NCT04577326)	Predecessor trial: 83% one-year OS, 72% ORR in mesothelioma (n=18 with pembrolizumab); CAR-T persistence >100 days in 39%	Recruiting
BNT327/PM8002 Bispecific Antibody	51.6% confirmed ORR (31 patients); 75% ORR in peritoneal cohort (8 patients, 100% DCR); Phase III registered July 2025	Phase III registered
ATOMIC-Meso (Pegargiminase)	Non-epithelioid: median OS 9.3 vs. 7.7 months (HR 0.71); three-year survival quadrupled; BLA under FDA review	FDA decision expected late 2026
UV1 Vaccine (NIPU Trial)	31% vs. 16% ORR; 15.4 vs. ~11 months median OS; FDA Fast Track February 2024	Phase III planning
ISM6331 (AI-Designed Drug)	Pan-TEAD inhibitor; first patient dosed January 2025 in China; FDA Orphan Drug Designation June 2024	Phase I recruiting

What Are Mesothelioma Clinical Trials?

Mesothelioma clinical trials are rigorously designed research studies that test new drugs, drug combinations, surgical techniques, radiation approaches, and medical devices in patients with malignant mesothelioma. These studies follow strict protocols approved by institutional review boards and monitored by the FDA to ensure patient safety while evaluating whether new treatments are more effective than existing standards of care.

Clinical trials progress through four phases, each serving a distinct purpose:

Phase	Purpose	Typical Size	Mesothelioma Trials (2026)
Phase I	Determine safe dosage and identify side effects	15-30 patients	23 recruiting
Phase I/II	Combined safety and early efficacy evaluation	30-100 patients	15 recruiting
Phase II	Evaluate treatment effectiveness and further assess safety	50-300 patients	19 recruiting
Phase III	Compare new treatment against current standard of care for FDA approval	300-3,000 patients	2 recruiting + VT3989 opening

Mesothelioma clinical trials are sponsored by pharmaceutical companies (such as AstraZeneca, Merck, and Bristol-Myers Squibb), the National Cancer Institute, academic medical centers (Memorial Sloan Kettering, MD Anderson, Dana-Farber), and biotechnology companies (Vivace Therapeutics, Insilico Medicine, Verismo Therapeutics). Only approximately 8% of eligible mesothelioma patients enroll in clinical trials, a participation rate that reflects geographic barriers to specialized cancer centers, lack of awareness about available trials, restrictive eligibility criteria, and the short treatment window available in a disease with a median survival of 12 to 18 months.

For patients considering their treatment options, clinical trials provide access to therapies that may offer superior outcomes compared to currently approved regimens. The three FDA-approved systemic treatments for pleural mesothelioma all emerged directly from successful clinical trials, and several investigational approaches now show response rates that exceed approved therapies.

What Phase III Trials Are Currently Recruiting for Mesothelioma?

Phase III trials represent the final stage of clinical testing before FDA approval. These large, randomized studies compare new treatments against the current standard of care. As of April 2026, two Phase III trials are actively recruiting for mesothelioma, with a third pivotal trial expected to begin enrollment in the first half of 2026.

eVOLVE-Meso (NCT06097728)

The eVOLVE-Meso trial is the largest actively enrolling Phase III trial in mesothelioma. This AstraZeneca-sponsored study evaluates volrustomig (MEDI5752), a novel PD-1/CTLA-4 bispecific antibody that provides simultaneous dual checkpoint blockade in a single molecule, combined with carboplatin and pemetrexed chemotherapy.

Trial specifications:

• Sponsor: AstraZeneca
• Design: Randomized, open-label, multicenter, global Phase III
• Enrollment target: 825 patients worldwide
• Experimental arm: Volrustomig + carboplatin/pemetrexed
• Comparator arms: Investigator's choice of platinum-based chemotherapy or nivolumab plus ipilimumab
• Primary endpoint: Overall survival (up to 61 months)
• Eligibility: Unresectable pleural mesothelioma, no prior systemic therapy, all histologies
• Locations: United States (Phoenix AZ, Duarte CA, Aurora CO, Jacksonville FL), Canada, Brazil, China, Europe, Japan
• Principal investigators: Marjorie G. Zauderer MD (Memorial Sloan Kettering); Arnaud Scherpereel MD (Lille University, France)

Key distinction: Volrustomig provides PD-1 and CTLA-4 blockade in a single molecule, which is mechanistically distinct from separately administered nivolumab plus ipilimumab. Efficacy data are not yet available; this trial is in active enrollment.

VT3989 Phase III — First TEAD Inhibitor Registrational Trial

VT3989, developed by Vivace Therapeutics, is the sole surviving TEAD inhibitor in mesothelioma development. The Phase III registrational trial is opening in the first half of 2026, making it the first-ever pivotal trial of a targeted therapy specifically designed for relapsed mesothelioma.

Phase I/II results at optimized dose (100 mg, 2-weeks-on/2-weeks-off; n=22):

• Objective response rate: 32% (7 of 22 partial responses)
• Disease control rate: 86% (19 of 22 patients with PR or SD)
• Median progression-free survival: 40 weeks (approximately 10 months) — more than double the approximately 15-week benchmark for standard-of-care in this setting
• Safety: Grade 3-4 treatment-related adverse events in only 8.7% of all 172 treated patients; proteinuria was reversible with dose adjustment
• Tumor types: Activity demonstrated in both NF2-mutant and NF2-wild-type tumors
• FDA designations: Orphan Drug (July 2025) and Fast Track (October 2025) for post-ICI, post-platinum mesothelioma
• Potential approval timeline: 2028-2029

VT3989 became the sole surviving TEAD inhibitor after Novartis discontinued IAG933 in October 2025 (13% ORR, dose-limiting QTc prolongation) and Ikena Oncology discontinued IK-930 in May 2024.

HIT-Meso (NCT05655078) — Proton Beam Therapy

HIT-Meso is a UK-only Phase III trial evaluating proton beam therapy for mesothelioma, the first randomized trial of this radiation approach in the disease.

Trial specifications:

• Sponsor: University College London
• Enrollment target: 148 patients
• Experimental arm: Proton beam therapy 50 Gy in 25 fractions with integrated boost to 60 Gy
• Control arm: Active surveillance (deferral of systemic therapy until progression)
• Co-primary endpoints: Progression-free survival and overall survival
• Eligibility: Histologically confirmed MPM; N0/N1 M0 disease; WHO PS 0-1; FEV1 and DLCO at least 40% predicted; no prior thoracic radiation or systemic therapy
• Sites: 18-20 UK NHS centers; proton beam therapy at UCLH (London) and The Christie (Manchester)
• Recruitment window: April 2024 through March 2027
• Note: U.S. patients cannot currently enroll in this trial

ATOMIC-Meso Results — BLA Under FDA Review

The ATOMIC-Meso trial (NCT02709512) has completed enrollment with practice-changing results published in JAMA Oncology in April 2024. Pegargiminase (ADI-PEG20) is an arginine depletion therapy targeting ASS1-deficient tumors, with a particular benefit for non-epithelioid mesothelioma.

Published results (249 non-epithelioid patients):

• Median overall survival: 9.3 months versus 7.7 months with placebo plus chemotherapy (HR 0.71, 95% CI 0.55-0.93; p=0.02)
• Median progression-free survival: 6.2 months versus 5.6 months (HR 0.65; p=0.02)
• Three-year survival: Quadrupled versus placebo arm
• Risk reduction: 35% reduction in progression risk

Regulatory status: Rolling BLA submission initiated late 2023; FDA Fast Track and Orphan Drug designations; BLA under FDA review with a decision anticipated late 2026 or early 2027. ASCO 2025 guidelines already include a conditional recommendation for pegargiminase plus chemotherapy for non-epithelioid patients who are not candidates for immunotherapy (Recommendation 4.4).

"The ATOMIC-Meso results represent a breakthrough for patients with non-epithelioid mesothelioma, a subtype that historically had very limited treatment options. Quadrupling three-year survival changes the outlook for these patients and their families. We urge anyone diagnosed with sarcomatoid or biphasic mesothelioma to discuss pegargiminase with their oncologist."

— Rod De Llano, Founding Partner, Danziger & De Llano

Phase III trial comparison:

Trial	NCT Number	Intervention	Population	Enrollment	Status
eVOLVE-Meso	NCT06097728	Volrustomig + chemo	First-line, all histologies	825	Recruiting
VT3989 Phase III	Phase I/II: NCT04665206	VT3989 TEAD inhibitor	Post-ICI, post-platinum	TBD	Opening H1 2026
HIT-Meso	NCT05655078	Proton beam therapy	Early-stage, UK only	148	Recruiting (UK)
ATOMIC-Meso	NCT02709512	Pegargiminase + chemo	Non-epithelioid	249 (complete)	BLA under FDA review

What CAR-T Cell Therapy Trials Are Available for Mesothelioma?

CAR-T (Chimeric Antigen Receptor T-cell) therapy represents one of the most promising frontiers in mesothelioma treatment. These engineered immune cells are programmed to recognize and attack cancer cells expressing specific surface proteins. Mesothelin, which is overexpressed in approximately 70-80% of epithelioid mesotheliomas, is the primary target for mesothelioma CAR-T trials. Five CAR-T or cell therapy programs are currently recruiting mesothelioma patients.

Memorial Sloan Kettering Intrapleural CAR-T (NCT04577326)

MSK pioneered the regional delivery of CAR-T cells directly into the pleural space, a method that maximizes tumor contact while minimizing systemic toxicity. The current trial tests M28z1XXPD1DNR, a next-generation CAR-T construct with a built-in dominant-negative PD-1 receptor that eliminates the need for concurrent checkpoint inhibitor therapy.

Trial details:

• Principal investigator: Prasad S. Adusumilli MD, Director of the Mesothelioma Program and Head of Solid Tumor Cell Therapy at MSK
• Phase: I dose-escalation
• CAR construct: M28z1XXPD1DNR (mesothelin-targeted with CD28 co-stimulatory domain + dominant-negative PD-1 receptor)
• Delivery: Intrapleural infusion via pleural catheter; minimum 48-hour inpatient monitoring
• Preconditioning: IV cyclophosphamide 1.5 g/m2 administered 2-7 days before infusion
• Eligibility: Epithelioid or biphasic MPM with at least 10% mesothelin expression by immunohistochemistry; at least one prior treatment line
• Location: Memorial Sloan Kettering Cancer Center, New York, NY

Breakthrough results from predecessor trial (NCT02414269): In 18 patients who received CAR-T cells plus pembrolizumab, the median overall survival from CAR-T infusion was 23.9 months (95% CI 14.7-NE), with an 83% one-year survival rate (95% CI 68-100%). The objective response rate was 72% in the mesothelioma subgroup (n=11), including 2 complete metabolic responses on PET. No on-target/off-tumor toxicity was observed.

NCI TNhYP218 CAR-T (NCT06885697)

This National Cancer Institute trial evaluates a novel CAR-T construct derived from T naive/stem cell memory cells, providing superior longevity and self-renewal compared to standard T effector memory cells. The hYP218 single-chain variable fragment targets a membrane-proximal region of mesothelin with increased tumor-killing capacity demonstrated in preclinical studies.

Trial details:

• Principal investigator: Raffit Hassan MD, Senior Investigator, NCI
• Phase: I dose-escalation with mesothelioma expansion cohort
• Design: 100-patient study; Arm 1 (dose escalation, all mesothelin-expressing solid tumors); Arm 2 (mesothelioma-only expansion at recommended Phase II dose)
• Delivery: Intravenous (systemic infusion) — contrasts with MSK's intrapleural approach
• Preconditioning: 7-day lymphodepletion with fludarabine plus cyclophosphamide
• Monitoring: 14-day inpatient monitoring; 15-year long-term safety follow-up per FDA requirement
• Eligibility: Mesothelin expression in at least 50% of tumor cells; at least one prior treatment; no history of lung fibrosis or serious autoimmune disease
• Location: NIH Clinical Center, Bethesda, Maryland
• Cost: All medical care provided at no cost to participants; some travel expenses may be covered

EVEREST-2 A2B694 (NCT06051695)

The EVEREST-2 trial evaluates A2B694, a logic-gated Tmod CAR-T cell therapy designed to virtually eliminate on-target, off-tumor toxicity. The CAR has two receptors: an activator that recognizes mesothelin on both tumor and normal cells, and a blocker that binds HLA-A*02, preventing activity against cells retaining HLA-A*02. Only tumor cells with HLA-A*02 loss of heterozygosity (LOH) are targeted.

Trial details:

• Sponsor: A2 Biotherapeutics
• Phase: I/II (first patient dosed April 24, 2024)
• Patient selection: Enrollment requires prescreening through BASECAMP-1 (NCT04981119) using next-generation sequencing via Tempus AI to identify HLA-A*02 LOH in tumor tissue — this adds 2-4 weeks to the pre-enrollment timeline
• Eligibility: HLA-A*02 LOH required in tumor; mesothelin-expressing solid tumors; at least one prior treatment
• Sites: Multiple U.S. locations

STAR-101 SynKIR-110 (NCT05568680)

The STAR-101 trial tests SynKIR-110, a KIR-based CAR-T cell therapy developed by Verismo Therapeutics. This multi-chain killer immunoglobulin-like receptor (KIR)-based CAR incorporates NK cell-like signaling, resulting in reduced exhaustion markers and superior serial killing in preclinical mesothelioma models.

Trial details:

• Phase: I dose-escalation
• Status: Cohorts 1-3 completed without dose-limiting toxicities as of May 2025; Cohort 4 ongoing
• FDA designations: Orphan Drug and Fast Track for mesothelioma
• Sites: University of Pennsylvania, MD Anderson Cancer Center, University of Kansas Cancer Center, University of Wisconsin Carbone Cancer Center
• Population: Advanced mesothelioma, ovarian cancer, or cholangiocarcinoma with mesothelin expression

For more information about how immunotherapy works in mesothelioma, see Immunotherapy_for_Mesothelioma.

CAR-T Trial	NCT Number	Target	Delivery	Key Requirement	Cost
MSK M28z1XXPD1DNR	NCT04577326	Mesothelin	Intrapleural	MSLN >=10% IHC	Standard
NCI TNhYP218	NCT06885697	Mesothelin	Intravenous	MSLN >=50% IHC	Free
EVEREST-2 A2B694	NCT06051695	Mesothelin (Tmod)	Intravenous	HLA-A*02 LOH	Standard
STAR-101 SynKIR-110	NCT05568680	Mesothelin (KIR-CAR)	Intravenous	MSLN expression	Standard

What Targeted Therapy and Emerging Trials Show Promise?

Beyond immunotherapy and CAR-T cell therapy, a new generation of targeted therapies is addressing specific molecular vulnerabilities in mesothelioma. These trials exploit genetic alterations such as NF2 mutations (targeting the Hippo/YAP/TEAD pathway), BAP1 loss (affecting chromatin remodeling), and MTAP deletion (creating a metabolic dependency).

VT3989 TEAD Inhibitor — Detailed Data

VT3989 is a first-in-class pan-TEAD palmitoylation inhibitor targeting the YAP/TEAD transcriptional activation pathway. NF2 mutations, present in approximately 40% of malignant pleural mesotheliomas, constitutively activate this pathway. However, VT3989 demonstrated activity in both NF2-mutant and NF2-wild-type tumors, suggesting broader applicability than initially expected.

Endpoint	Result (n=22, optimized dose)
Objective response rate	32% (7/22 partial responses)
Disease control rate	86% (19/22 PR or SD)
Median progression-free survival	40 weeks (~10 months)
Duration of response	8 patients on treatment >1 year; 1 approaching 2 years
Grade 3-4 TRAEs (all patients)	8.7% (n=172 total treated)
Selected Phase III dose	100 mg once daily, 2-weeks-on/2-weeks-off

ISM6331 — First AI-Designed Drug for Mesothelioma (NCT06566079)

ISM6331 is a pan-TEAD inhibitor designed using Insilico Medicine's Chemistry42 artificial intelligence platform, making it the first AI-designed drug to enter clinical testing for mesothelioma. The compound reached first-in-human dosing on January 22, 2025, in China — less than five years from AI platform launch to clinical trial, compared to the typical ten to fifteen year drug development timeline.

Key milestones:

• June 2024: FDA Orphan Drug Designation granted
• August 2024: IND clearance received
• January 22, 2025: First patient dosed in China
• 2026: U.S. enrollment expected
• Mechanism: Pan-TEAD inhibitor blocking the palmitoylation site, disrupting YAP/TAZ-TEAD transcriptional activity

Tazemetostat for BAP1-Loss Mesothelioma (NCT02860286)

Tazemetostat is an EZH2 inhibitor being evaluated in patients with BAP1-deficient mesothelioma. BAP1 loss occurs in 60-80% of mesotheliomas and disrupts chromatin remodeling, creating a vulnerability to EZH2 inhibition. Tazemetostat is already FDA-approved for epithelioid sarcoma (a related BAP1/INI1 alteration), providing a regulatory precedent.

• Status: Enrollment complete; results under analysis; expected in 2026
• Sites: Dana-Farber Cancer Institute, Emory Winship Cancer Institute, and other academic centers
• Eligibility: Relapsed/refractory mesothelioma with BAP1 loss (any anatomic site including peritoneal)

Tulmimetostat/CPI-0209 (NCT04104776)

Tulmimetostat is a next-generation dual EZH2/EZH1 inhibitor with potentially broader chromatin remodeling effects than tazemetostat. Preliminary Phase II results (ASCO 2024, data cutoff October 15, 2023) showed 1 partial response among 29 evaluable patients, meeting Stage 2 expansion eligibility criteria.

• Sponsor: Jazz Pharmaceuticals (formerly Constellation Pharmaceuticals)
• Sites: Emory Winship, University of Chicago, University of Maryland, Massachusetts General Hospital, Dana-Farber
• Population: Cohort M5 — relapsed/refractory malignant pleural or peritoneal mesothelioma with BAP1 loss

MRTX1719 for MTAP-Deleted Mesothelioma (NCT05245500)

MRTX1719 is an MTA-cooperative PRMT5 inhibitor selectively active in MTAP-deleted tumors. MTAP deletion occurs in approximately 25% of mesotheliomas and creates a metabolic vulnerability that MRTX1719 exploits.

• Sponsor: Bristol Myers Squibb (acquired Mirati Therapeutics)
• Phase: I (multiple expansion cohorts)
• Sites: Mayo Clinic (Phoenix, Jacksonville, Rochester), Sarah Cannon Research Institute (Denver, Orlando), Rocky Mountain Cancer Centers

UV1 Telomerase Vaccine (NIPU Trial Results)

The NIPU Phase II trial (NCT04300244) randomized 118 patients with previously treated mesothelioma to nivolumab plus ipilimumab with or without UV1, an off-the-shelf synthetic peptide vaccine targeting hTERT (expressed in 85-90% of all cancers). No HLA pre-screening is required. UV1 earned FDA Fast Track designation in February 2024.

Endpoint	UV1 + Nivo/Ipi	Nivo/Ipi Alone
Objective response rate	31%	16%
Median overall survival	15.4 months	~11 months
Death risk reduction	27% (secondary endpoint)	Reference

TTFields/Optune Lua

TTFields (tumor treating fields), delivered via the Optune Lua device (Novocure), received FDA Humanitarian Device Exemption (HDE) approval on May 23, 2019, for adult patients with unresectable, locally advanced or metastatic pleural mesothelioma used concurrently with pemetrexed plus platinum chemotherapy. The approval was based on the STELLAR trial (NCT02397928).

STELLAR results (80 patients, single-arm Phase II):

• Median OS: 18.2 months (95% CI 12.1-25.8)
• One-year OS: 62.2%
• Median PFS: 7.6 months
• ORR: 40%
• Disease control rate: 97%

Important limitations: STELLAR had no randomized control group and compared results to historical controls from 2003. The FDA's approval statement noted that "effectiveness of this device for this use has not been demonstrated." No Phase III randomized controlled trial of TTFields in mesothelioma has been registered or announced as of April 2026. NCCN (v2.2025) and ASCO 2025 guidelines do not prominently feature TTFields in mesothelioma treatment recommendations, reflecting the absence of Phase III data.

BNT327/PM8002 Bispecific Antibody

BNT327/PM8002 is a PD-L1/VEGF-A bispecific antibody that demonstrated remarkable activity in mesothelioma, with particularly exceptional results in peritoneal mesothelioma.

Phase II results (31 patients with unresectable mesothelioma):

• Confirmed overall response rate: 51.6%
• Peritoneal mesothelioma cohort (8 patients): 75% ORR, 100% disease control rate
• Median exposure: 16.0 months (95% CI 8.1-19.5)
• Median follow-up: 19.3 months
• Safety: 93.5% experienced grade 3/4 adverse events; no treatment-related deaths
• Phase III trial: Registered July 2025 (NCT07133750)

Exceptional peritoneal results: BNT327/PM8002 achieved a 75% objective response rate with 100% disease control in 8 peritoneal mesothelioma patients — among the highest response rates ever reported in this rare subtype. A Phase III trial (NCT07133750) was registered in July 2025.

What Trials Are Available for Peritoneal Mesothelioma?

Peritoneal mesothelioma accounts for approximately 10-15% of all mesothelioma diagnoses and has a distinct treatment landscape from pleural disease. While cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) remains the standard of care for eligible patients, several clinical trials now offer additional options.

CRS-HIPEC Outcomes

Cytoreductive surgery with HIPEC remains the gold standard for resectable peritoneal mesothelioma. Published data from specialized centers demonstrate:

• Median overall survival: 53 months (approximately 4.4 years)
• Five-year survival: 47% in selected patients
• Best candidates: Completeness of cytoreduction index (CC-0 or CC-1), epithelioid histology, low peritoneal cancer index

ICARuS II (NCT06057935)

The ICARuS II trial evaluates intraperitoneal chemotherapy following cytoreductive surgery for peritoneal mesothelioma.

• Chemotherapy agents: Pemetrexed, cisplatin, or carboplatin delivered intraperitoneally after CRS
• Sites: University of Chicago, University of Michigan, Washington University (St. Louis), University of Nebraska, Rutgers University

PIPAC with Nab-Paclitaxel (NCT07253662)

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) represents a novel drug delivery method that uses aerosolized chemotherapy delivered under pressure during laparoscopy, allowing for more homogeneous drug distribution across peritoneal surfaces.

• Sponsor: Cedars-Sinai Medical Center
• Phase: I/II
• Drug: Nab-paclitaxel delivered via PIPAC, repeated every 6 weeks
• Location: Cedars-Sinai Medical Center, Los Angeles, California

BNT327/PM8002 Peritoneal Cohort

As noted in the targeted therapy section, BNT327/PM8002 achieved a 75% objective response rate with 100% disease control rate in 8 peritoneal mesothelioma patients — among the most promising results ever reported in this subtype. A Phase III trial (NCT07133750) was registered in July 2025.

Real-World ICI Data for Peritoneal Mesothelioma

A French real-world study (published European Journal of Cancer, December 2025) demonstrated that immune checkpoint inhibitors achieve a median overall survival of 16.8 months in unresectable peritoneal mesothelioma. The ASCO 2025 guidelines have extended immunotherapy recommendations to peritoneal mesothelioma patients who are candidates for systemic therapy, though they acknowledge limited peritoneal-specific trial evidence.

Important for peritoneal patients: Most major Phase III mesothelioma trials (eVOLVE-Meso, CheckMate 743, KEYNOTE-483) enrolled primarily pleural mesothelioma patients. Peritoneal patients should discuss trial options with a peritoneal mesothelioma specialist, as eligibility and optimal treatment sequencing differ from pleural disease. See Peritoneal_Mesothelioma for more information.

Am I Eligible for a Mesothelioma Clinical Trial?

Eligibility for mesothelioma clinical trials depends on several factors including disease stage, histological subtype, prior treatments, performance status, organ function, and specific biomarker profiles. Understanding these requirements helps patients and their oncologists identify the most appropriate trials before contacting trial coordinators.

Stage-Specific Eligibility

Stage	Available Trial Types	Key Considerations
Stage I-II	Perioperative/neoadjuvant trials (surgery-based); first-line systemic therapy trials; proton beam therapy (HIT-Meso, UK only)	Patients with early-stage disease have the broadest trial options including surgical approaches. The Johns Hopkins perioperative nivolumab plus ipilimumab trial demonstrated 28.6 months median OS in the combination arm.
Stage III	Most systemic therapy trials (eVOLVE-Meso, KEYNOTE-483 regimen); potentially perioperative trials at select centers; targeted therapy and immunotherapy combinations	Stage III patients are eligible for the majority of first-line systemic therapy trials. Some perioperative approaches may still be available depending on the extent of disease and surgeon assessment.
Stage IV	Systemic therapy only (immunotherapy, targeted therapy, CAR-T); compassionate use possible for late-stage patients	Stage IV patients are generally limited to systemic approaches. Compassionate use or expanded access programs may be available for patients who do not meet standard trial criteria. Contact the trial sponsor directly to inquire.

For detailed staging information, see Mesothelioma_Diagnosis_and_Staging.

General Laboratory and Performance Requirements

Most mesothelioma clinical trials require patients to meet baseline laboratory values and performance criteria. The following thresholds are representative of Phase II and Phase III trial requirements:

Requirement	Typical Standard	Notes
ECOG performance status	0-1 (some Phase I trials accept 2)	See ECOG table below
Absolute neutrophil count (ANC)	>=1,500/uL	Recent CBC required
Platelet count	>=100,000/uL	Recent CBC required
Hemoglobin	>=9.0 g/dL	Some trials accept >=8.0 g/dL
Creatinine clearance	>=45 mL/min	Calculated by Cockcroft-Gault formula
Total bilirubin	<=1.5x upper limit of normal (ULN)	Recent chemistry panel required
ALT/AST	<=5x ULN	Liver function assessment
Life expectancy	>=12 weeks (Phase II/III)	Some Phase I trials accept >=4 weeks

ECOG Performance Status

ECOG Grade	Description	Trial Eligibility
0	Fully active; no restrictions on pre-disease activities	Eligible for virtually all trials
1	Restricted in strenuous activity but ambulatory; able to carry out light work	Eligible for most trials including Phase III
2	Ambulatory; all self-care; unable to work; up >50% of waking hours	Some Phase I trials and supportive care studies accept PS2
3	Limited self-care; confined to bed/chair >50% of waking hours	Generally excluded from interventional trials
4	Completely disabled; no self-care	Excluded from essentially all interventional trials

Histology-Specific Eligibility

Histology	Eligible Trials	Key Exclusions
Epithelioid	Broadest options: eVOLVE-Meso, all ICI trials, VT3989, BAP1-targeted trials, CAR-T (if mesothelin >=10%), UV1 vaccine, BNT327	ATOMIC-Meso (non-epithelioid specific)
Sarcomatoid	ATOMIC-Meso (pegargiminase), VT3989, MRTX1719 (if MTAP-deleted), some ICI trials	CAR-T trials (sarcomatoid tumors typically do not express mesothelin)
Biphasic	Most systemic therapy trials; CAR-T (if mesothelin >=10%); ATOMIC-Meso (non-epithelioid); VT3989	Some trials may specify histology; check individual protocol
Peritoneal	Tazemetostat (includes all sites); tulmimetostat Cohort M5 (includes peritoneal); HIPEC/CRS trials; PIPAC; BNT327	Most Phase III ICI trials enrolled primarily pleural patients

Biomarker Requirements

Molecular profiling through next-generation sequencing (NGS) is increasingly critical for determining targeted therapy trial eligibility. Patients should request comprehensive biomarker testing before exploring targeted therapy trials.

Biomarker	Prevalence in MPM	Testing Method	Required For
BAP1 loss	60-80%	IHC or NGS	Tazemetostat, tulmimetostat Cohort M5, olaparib HRD trial
MTAP deletion	~25%	NGS	MRTX1719
Mesothelin expression	70-80% (epithelioid)	IHC (>=10% for MSK; >=50% for NCI)	All CAR-T trials
NF2 mutation	30-50%	NGS	VT3989 (not required but enriches population)
ASS1 deficiency	Common in non-epithelioid	IHC	Pegargiminase/ATOMIC-Meso
HLA-A*02 LOH	~30-40% of HLA-A*02+ patients	NGS via BASECAMP-1	EVEREST-2 A2B694 CAR-T

ASCO 2025 guideline note: PD-L1, TMB, and MSI status should NOT be used to determine choice of chemotherapy versus immunotherapy in malignant pleural mesothelioma (Recommendation 3.5.3). Germline BAP1 testing is recommended for all mesothelioma patients (Recommendation 7.1, high evidence quality).

Prior Treatment Requirements by Trial Type

Trial Category	Prior Treatment Requirement
First-line trials (eVOLVE-Meso)	Treatment-naive (no prior systemic therapy for MPM)
Second-line immunotherapy trials (NIPU/UV1)	At least 1 prior platinum-based chemotherapy regimen
CAR-T trials (all four programs)	At least 1 prior treatment regimen; no prior CAR-T therapy
VT3989 TEAD inhibitor	At least 1 prior ICI AND at least 1 prior platinum-based therapy (post-ICI, post-platinum)
EZH2 inhibitor trials (tazemetostat, tulmimetostat)	At least 1 prior treatment; relapsed/refractory disease
Phase I dose-escalation (MRTX1719, ISM6331)	Variable; typically at least 1 prior regimen; confirm by individual protocol

Important: Eligibility requirements vary significantly between trials. A patient who does not qualify for one trial may be eligible for others. Work with a mesothelioma specialist to identify all available options. Pre-screening is free and does not obligate enrollment.

How Do I Find and Enroll in a Mesothelioma Clinical Trial?

The clinical trial enrollment process typically follows seven stages, from initial consultation through treatment initiation. Understanding each step helps reduce delays and increases the likelihood of successful enrollment.

Step 1: Confirm Your Diagnosis and Staging

Gather your complete medical records including your pathology report (with histological subtype — epithelioid, sarcomatoid, or biphasic), all imaging reports (CT, PET, MRI), laboratory work, and any molecular profiling results (BAP1, MTAP, mesothelin expression, NF2 status). Trial coordinators will need these documents to assess eligibility. For more information, see Mesothelioma_Diagnosis_and_Staging.

Step 2: Ask Your Oncologist About Trial Eligibility

Even if your oncologist does not mention clinical trials, you can ask proactively. Key questions include:

• "Are there any Phase I-III trials I might be eligible for based on my pathology and ECOG status?"
• "Do you know my BAP1, MTAP, and mesothelin status? Do I need biomarker testing to access targeted trials?"
• "Can you refer me to an NCI-designated cancer center for a second opinion and trial evaluation?"
• "Which trials in my area are actively enrolling right now?"
• "What is the expected treatment burden — travel, visits, and time commitments?"

Step 3: Search ClinicalTrials.gov

Navigate to ClinicalTrials.gov and follow these steps:

1. Enter search terms: "mesothelioma" OR "malignant pleural mesothelioma" OR "peritoneal mesothelioma" (depending on your diagnosis)
2. Apply filters: Status = Recruiting only; Phase = Phase 2 and Phase 3 for trials closest to FDA approval; Location = your city/state with 100-300 mile radius
3. Review key fields for each result: status (must say "Recruiting"), primary completion date (should be in the future), eligibility criteria (review both inclusion and exclusion lists)
4. Note the unique NCT number for each trial and share it with your oncologist

Step 4: Contact the Trial Coordinator

Each trial listing on ClinicalTrials.gov includes contact information for the trial site coordinator. Call or email to discuss your case. The coordinator will conduct an initial telephone review of your medical history against the inclusion/exclusion criteria.

Step 5: Pre-Screening Phone Call

The trial site coordinator reviews your medical records against eligibility criteria. This may require submission of pathology slides or tumor blocks for biomarker testing. Pre-screening is free and does not obligate enrollment. Some trials (such as EVEREST-2/A2B694) require a separate prescreening study that adds 2-4 weeks.

Step 6: In-Person Screening Visit (Baseline Assessments)

Complete baseline assessments including bloodwork, imaging (CT/PET/MRI), performance status assessment (ECOG scoring), cardiac evaluation, and any protocol-required tests. The baseline period typically takes one to two weeks.

Step 7: Informed Consent and Enrollment

Read the full informed consent document carefully. Ask questions about risks, benefits, alternative treatments, and your right to withdraw at any time without penalty to your care. Once you sign informed consent, you begin treatment according to the assigned protocol with regular study visits and monitoring.

Trial Search Resources

Resource	URL	Key Features
ClinicalTrials.gov	clinicaltrials.gov	Authoritative U.S. federal registry; legally required listing for all U.S. trials
NCI Cancer.gov Trial Finder	cancer.gov	Patient-friendly interface; 12,000+ trials; NCI-sponsored trial detail
MesoRFA.org	mesorfa.org | Phone: (800) 909-MESO	"10-Step Guide: How to Find and Choose a Mesothelioma Clinical Trial" (free publication); financial assistance resources

What Financial Assistance Is Available for Trial Participants?

Understanding the financial landscape of clinical trial participation helps patients make informed decisions about enrollment. Federal law protects patients from many trial-related costs, and multiple assistance programs exist specifically for mesothelioma patients.

What Trials Cover Versus What Patients Pay

Cost Category	Covered By	Examples
Research costs	Trial sponsor (pharmaceutical company, NIH, university)	Experimental drug; extra protocol-required tests; data collection activities; additional study procedures
Routine patient care	Patient's health insurance	Standard drugs and procedures; medical care for administering treatment; care for trial-related complications; standard lab work and imaging
Travel and lodging	Not typically covered by insurance; may be covered by sponsor programs or patient assistance organizations	Transportation; hotel stays; meals during visits

Key principle: Patients should never have to pay for the experimental drug itself — this is always covered by the trial sponsor.

Insurance Protections

Affordable Care Act (ACA): The ACA requires most private health insurance plans and Marketplace plans to cover routine patient care costs associated with qualifying clinical trials. Insurers cannot deny participation, limit coverage, or charge more because a patient enrolls in a trial. Most Phase II and III mesothelioma trials registered on ClinicalTrials.gov qualify under these protections.

Medicare: Medicare Parts A and B cover routine care costs in qualifying clinical trials. Part A covers inpatient hospital stays required by trial participation, and Part B covers outpatient care, doctor visits, and standard chemotherapy in clinical settings. Patients typically pay approximately 20% of approved costs after meeting the Part B deductible. Medicare does not cover research costs — these are covered by the sponsor.

Private insurance: Forty-four states have enacted laws mandating clinical trial cost coverage. Contact your insurer before enrollment to verify coverage specifics.

Medicaid: No federal mandate exists for Medicaid coverage of routine trial costs, but the majority of states cover at least routine costs for Medicaid beneficiaries in qualifying trials. Contact your state Medicaid office for specific coverage policies.

VA benefits: Veterans enrolled in VA healthcare can participate in clinical trials and receive routine care through the VA system. The VA covers standard medical costs associated with trial participation for eligible veterans.

Travel and Financial Assistance Programs

Program	Description	Contact
NCI/NIH Free Care	TNhYP218 CAR-T trial (NCT06885697) provides all medical care at no cost; some travel and lodging may be covered	clinicalcenter.nih.gov
Lazarex Cancer Foundation	Financial assistance for travel costs associated with clinical trial participation	lazarex.org
Merck Patient Assistance (Keytruda)	Access to pembrolizumab for eligible uninsured or underinsured patients	merckaccessprogram-keytruda.com
BMS Patient Assistance (Opdivo/Yervoy)	Access to nivolumab and ipilimumab for eligible patients	bmspaf.org
MesoRFA Financial Resources	Compiled financial assistance resources for mesothelioma patients and families	(800) 909-6376; mesorfa.org

What Trials Are Opening in 2026?

The mesothelioma clinical trial landscape continues to expand in 2026, with several landmark trials opening and key regulatory decisions anticipated.

New Trial Openings

VT3989 Phase III (H1 2026): The first-ever registrational Phase III trial of a targeted therapy for mesothelioma. VT3989 will be tested in the post-ICI, post-platinum setting where 32% objective response rate was demonstrated in Phase I/II. If the trial meets its primary endpoint, FDA approval could follow in 2028-2029.

BNT327/PM8002 Phase III (NCT07133750): Registered July 2025, this pivotal trial will evaluate the PD-L1/VEGF-A bispecific antibody that achieved 51.6% overall response rate in Phase II. The Phase III is expected to begin enrollment in 2026.

ISM6331 U.S. enrollment: Following initial enrollment in China beginning January 2025, the AI-designed TEAD inhibitor is expected to begin enrolling U.S. patients in 2026.

MVdeltaC measles-based immunotherapy: A novel oncolytic measles virus platform received FDA Orphan Drug Designation in June 2025 for mesothelioma. Early-phase trials are anticipated at Mayo Clinic sites.

Key Regulatory and Data Milestones

Pegargiminase FDA decision (late 2026/early 2027): The BLA for pegargiminase based on ATOMIC-Meso results is under FDA review. If approved, it would be the first targeted therapy specifically for non-epithelioid mesothelioma and the first new mesothelioma FDA approval since September 2024.

Tazemetostat results (expected 2026): Results from the Phase II trial (NCT02860286) of tazemetostat in BAP1-deficient mesothelioma are expected, which will define the future role of EZH2 inhibition in this molecular subgroup.

Antibody-drug conjugates: Several ADC programs are advancing including sacituzumab govitecan (NCT06477419, TROP-2 targeted, Memorial Sloan Kettering) and rinatabart sesutecan.

Event	Expected Timing	Significance
VT3989 Phase III opens	H1 2026	First targeted therapy Phase III in mesothelioma
BNT327 Phase III enrollment begins	2026	Phase III for bispecific antibody with 51.6% ORR
ISM6331 U.S. enrollment	2026	First AI-designed mesothelioma drug in U.S. patients
Pegargiminase FDA decision	Late 2026/early 2027	First approval for non-epithelioid mesothelioma
Tazemetostat Phase II results	2026	EZH2 inhibition in BAP1-loss mesothelioma
MVdeltaC early trials	2026	Oncolytic virus approach with FDA Orphan Drug status

What Are the Latest FDA-Approved Treatments from Clinical Trials?

Every currently approved systemic treatment for malignant pleural mesothelioma was established through clinical trials. The following timeline documents the four major regulatory approvals and the trials that enabled them.

Year	Treatment	Pivotal Trial	Key Results	Approval Type
2004	Cisplatin + pemetrexed	EMPHACIS (Vogelzang 2003)	Median OS 12.1 vs. 9.3 months; first systemic therapy for MPM	Full FDA approval
May 2019	TTFields/Optune Lua	STELLAR (Ceresoli 2019)	Median OS 18.2 months; 62.2% one-year OS; single-arm, no RCT control	HDE only (H180002)
October 2020	Nivolumab + ipilimumab	CheckMate 743 (Baas 2021)	Median OS 18.1 vs. 14.1 months (HR 0.74); non-epithelioid: 18.1 vs. 8.8 months (HR 0.46)	Full FDA approval
September 2024	Pembrolizumab + pemetrexed + platinum	KEYNOTE-483 / IND.227	Median OS 17.3 vs. 16.1 months (HR 0.79); ORR 52% vs. 29%; non-epithelioid HR 0.57	Full FDA approval

CheckMate 743 Five-Year Update (February 2026)

The five-year update of CheckMate 743, published by Scherpereel et al. in the Journal of Clinical Oncology in February 2026, represents the longest follow-up data ever reported for first-line immunotherapy in pleural mesothelioma (median follow-up 66.8 months).

Endpoint	Nivolumab + Ipilimumab	Chemotherapy	HR (95% CI)
Median OS	18.1 months	14.1 months	0.74 (0.62-0.88)
Five-year OS	14%	6%	—
Epithelioid five-year OS	14%	8%	0.85 (0.69-1.03)
Non-epithelioid five-year OS	12%	1%	0.48 (0.33-0.68)
Five-year PFS	8%	0%	—
Responders with ongoing response at 5 years	17%	0%	—

The five-year data confirm that nivolumab plus ipilimumab provides the most durable survival benefit of any first-line regimen in mesothelioma. In non-epithelioid disease, 12% of immunotherapy-treated patients were alive at five years compared to just 1% receiving chemotherapy — establishing dual immunotherapy as the unequivocal standard of care for sarcomatoid and biphasic histologies. For detailed immunotherapy information, see Immunotherapy_for_Mesothelioma.

KEYNOTE-483 Key Results

The KEYNOTE-483 trial (N=440, Phase III component) established pembrolizumab plus chemotherapy as a new first-line standard for pleural mesothelioma:

• Median OS: 17.3 months versus 16.1 months (HR 0.79, 95% CI 0.64-0.98; p=0.0324)
• Three-year OS: 25% versus 17%
• ORR (BICR-assessed): 52% versus 29% (p<0.00001)
• Non-epithelioid median OS: 12.3 months versus 8.2 months (HR 0.57, 95% CI 0.36-0.89)

January 2026 update: The FDA approved Keytruda QLEX (subcutaneous pembrolizumab) on January 11, 2026, offering a one-minute injection every three weeks as an alternative to IV infusion for all 38 pembrolizumab indications including mesothelioma.

"Clinical trials represent the cutting edge of mesothelioma treatment. We encourage every patient to explore trial options because tomorrow's standard treatments are available today through these programs. The survival improvements we are seeing — 14% alive at five years with immunotherapy, 83% one-year survival with CAR-T cells, 32% response rates with TEAD inhibitors — were unimaginable just a decade ago."

— Paul Danziger, Founding Partner, Danziger & De Llano

Diagnosed with Mesothelioma? Get Help Today. If you or a loved one has been diagnosed with mesothelioma, you may be entitled to compensation from asbestos trust funds, settlements, or verdicts — and pursuing legal action does not affect your eligibility for clinical trials. Call Danziger & De Llano for a free, confidential case review: (866) 222-9990 Click Here for a Free Case Review

Frequently Asked Questions

What clinical trials are available for Stage 3 mesothelioma patients?

Stage III mesothelioma patients are eligible for the majority of first-line systemic therapy trials, including the eVOLVE-Meso Phase III trial (NCT06097728) evaluating volrustomig plus chemotherapy. Stage III patients may also qualify for second-line trials such as VT3989 after initial treatment, all four active CAR-T programs (if they meet mesothelin expression thresholds), and targeted therapy trials based on their molecular profile. While most surgical perioperative trials target earlier-stage disease, some centers evaluate Stage III patients on a case-by-case basis depending on the extent of tumor involvement.

Can mesothelioma patients with prior chemotherapy qualify for clinical trials?

Yes. Many clinical trials specifically require prior chemotherapy as an eligibility criterion. All four CAR-T trials require at least one prior treatment line, VT3989 requires both prior immunotherapy and prior platinum-based chemotherapy, and EZH2 inhibitor trials (tazemetostat, tulmimetostat) require relapsed or refractory disease. First-line trials such as eVOLVE-Meso require treatment-naive patients, but the majority of Phase I and Phase II trials accept previously treated patients. Having received prior chemotherapy expands rather than limits trial options in the second-line and beyond settings.

What is the VT3989 clinical trial for mesothelioma?

VT3989 is a first-in-class TEAD inhibitor developed by Vivace Therapeutics that targets the Hippo/YAP/TEAD pathway, which is dysregulated in the majority of mesotheliomas. In Phase I/II testing at the optimized dose (100 mg, two-weeks-on/two-weeks-off) in 22 mesothelioma patients, VT3989 achieved a 32% objective response rate, 86% disease control rate, and approximately 10-month median progression-free survival. The drug holds FDA Orphan Drug and Fast Track designations. A Phase III registrational trial is opening in the first half of 2026 for patients who have progressed after immunotherapy and platinum-based chemotherapy, with potential FDA approval in 2028-2029.

How long does it take to get into a mesothelioma clinical trial?

The enrollment timeline from initial interest to first treatment typically ranges from two to six weeks. The process includes gathering medical records (one to two days), pre-screening phone consultation with the trial coordinator (one to three days), submission of pathology and imaging for review (one to two weeks), in-person screening visit with baseline assessments (one to two weeks), and informed consent review and enrollment. Some trials add additional steps: EVEREST-2 requires prescreening through BASECAMP-1, which adds two to four weeks for HLA-A*02 LOH testing. Patients should begin exploring trials as early as possible after diagnosis to maximize their treatment window.

What is the ISM6331 AI-designed drug for mesothelioma?

ISM6331 is a pan-TEAD inhibitor created using Insilico Medicine's Chemistry42 artificial intelligence platform, making it the first AI-designed drug to enter clinical testing for mesothelioma. The compound received FDA Orphan Drug Designation in June 2024 and IND clearance in August 2024. The first patient was dosed on January 22, 2025, in China, with U.S. enrollment expected in 2026. Notably, ISM6331 progressed from AI platform launch to first-in-human dosing in under five years, compared to the typical ten to fifteen year drug development timeline, demonstrating the potential of AI-accelerated drug design in rare cancers.

Can I participate in a clinical trial if I have already had surgery?

Yes. Prior surgery does not automatically disqualify patients from clinical trials. Most systemic therapy trials (immunotherapy, targeted therapy, CAR-T) accept patients who have undergone prior surgical resection. In fact, some trials specifically target the post-surgical setting: the Johns Hopkins perioperative nivolumab plus ipilimumab trial evaluates immunotherapy both before and after surgery. The key factors are whether the patient has measurable disease remaining (required for most response-based trials), adequate performance status (ECOG 0-1), and sufficient recovery from surgical complications. Patients should discuss their surgical history with the trial coordinator during pre-screening.

What happens to my treatment if the clinical trial is discontinued?

If a clinical trial is discontinued, the trial sponsor is obligated to ensure a safe transition for enrolled patients. Options typically include: transition to the standard-of-care treatment, continued access to the experimental drug through a compassionate use or expanded access program (if the drug showed individual benefit), referral to alternative clinical trials, or enrollment in the sponsor's long-term safety follow-up. The informed consent document details these provisions before enrollment begins. Patients retain the right to receive ongoing medical care regardless of trial status, and discontinuation of a trial does not mean the treatment was ineffective for all participants.

Are there clinical trials for peritoneal mesothelioma?

Yes. Several trials are specifically designed for or include peritoneal mesothelioma patients. The ICARuS II trial (NCT06057935) evaluates intraperitoneal chemotherapy after cytoreductive surgery at five U.S. academic centers. The PIPAC trial (NCT07253662) at Cedars-Sinai tests aerosolized intraperitoneal chemotherapy. BNT327/PM8002 achieved a remarkable 75% objective response rate in 8 peritoneal patients, with a Phase III trial registered. Tazemetostat (NCT02860286) and tulmimetostat (NCT04104776) both include peritoneal mesothelioma patients. CRS-HIPEC at specialized centers achieves median overall survival of 53 months with 47% five-year survival in selected patients.

What is the STELLAR trial for mesothelioma?

The STELLAR trial (NCT02397928) was a Phase II, single-arm study that evaluated tumor treating fields (TTFields) using the Optune Lua device in combination with pemetrexed plus platinum chemotherapy in 80 patients with unresectable malignant pleural mesothelioma across 12 European sites. Results showed median overall survival of 18.2 months, 62.2% one-year survival, and a 97% disease control rate. The FDA granted Humanitarian Device Exemption approval in May 2019 based on these results. However, the trial had no randomized control group and was compared to 2003 historical data. No Phase III randomized controlled trial has been registered as of 2026, and major guidelines (ASCO 2025, NCCN v2.2025) do not prominently feature TTFields based on the absence of Phase III data.

How does tumor treating fields (TTFields) work in mesothelioma trials?

TTFields deliver low-intensity, intermediate-frequency alternating electric fields to the tumor region through adhesive electrode arrays (transducer arrays) placed on the patient's torso. These electric fields disrupt cell division by interfering with the mitotic spindle and cell membrane integrity in rapidly dividing cancer cells, while sparing normal cells that divide more slowly. In the STELLAR trial, patients wore the device for a median of 16.3 hours per day. The treatment is continuous and portable, allowing patients to maintain daily activities during treatment. Real-world compliance averages approximately 12.5 hours per day, and device cost is approximately $21,000 per month, with inconsistent Medicare and private insurance coverage for the mesothelioma HDE indication.

What is eVOLVE-Meso and who qualifies?

eVOLVE-Meso (NCT06097728) is the largest actively recruiting Phase III trial in mesothelioma, sponsored by AstraZeneca. It evaluates volrustomig (MEDI5752), a bispecific antibody that simultaneously blocks PD-1 and CTLA-4 in a single molecule, combined with carboplatin and pemetrexed chemotherapy. The trial is enrolling 825 patients worldwide at sites across the United States, Canada, Brazil, China, Europe, and Japan. To qualify, patients must have unresectable malignant pleural mesothelioma with no prior systemic therapy, adequate organ function (ECOG 0-1), and histologically confirmed disease of any subtype. No efficacy data are available yet as the trial is in active enrollment.

Can veterans access mesothelioma clinical trials through the VA?

Yes. Veterans enrolled in VA healthcare can participate in clinical trials and receive routine care through the VA system. The VA covers standard medical costs associated with trial participation for eligible veterans. Additionally, the NCI's TNhYP218 CAR-T trial (NCT06885697) at the NIH Clinical Center in Bethesda, Maryland, provides all medical care at no cost and covers some travel expenses, making it particularly accessible for veterans. Veterans with service-connected mesothelioma receive 100% disability rating and associated benefits. The VA Cooperative Studies Program also sponsors clinical research, and VA hospitals at locations including Houston, Boston, and Los Angeles serve as sites for mesothelioma trials. Veterans should contact their VA oncologist or the Veterans Health Administration at 1-877-222-8387 to discuss trial options.

NCT Verification Table

The following table lists all NCT numbers referenced in this article with their trial name and current status as of April 2026.

NCT Number	Trial Name	Category	Status (April 2026)
NCT06097728	eVOLVE-Meso (Volrustomig)	Immunotherapy Phase III	Recruiting
NCT04665206	VT3989 (TEAD Inhibitor)	Targeted Therapy Phase I/II	Recruiting; Phase III opening H1 2026
NCT05655078	HIT-Meso (Proton Beam Therapy)	Radiation Phase III	Recruiting (UK only)
NCT02709512	ATOMIC-Meso (Pegargiminase)	Targeted Therapy Phase II/III	Completed; BLA under FDA review
NCT04577326	MSK Intrapleural CAR-T (M28z1XXPD1DNR)	CAR-T Phase I	Recruiting
NCT06885697	NCI TNhYP218 CAR-T	CAR-T Phase I	Recruiting (FREE)
NCT06051695	EVEREST-2 A2B694 (Logic-gated Tmod)	CAR-T Phase I/II	Recruiting
NCT05568680	STAR-101 SynKIR-110 (KIR-CAR)	CAR-T Phase I	Recruiting
NCT06566079	ISM6331 (AI-Designed TEAD Inhibitor)	Targeted Therapy Phase I	Recruiting
NCT02860286	Tazemetostat (EZH2 Inhibitor)	Targeted Therapy Phase II	Enrollment complete
NCT04104776	Tulmimetostat/CPI-0209	Targeted Therapy Phase I/II	Recruiting
NCT05245500	MRTX1719 (PRMT5 Inhibitor)	Targeted Therapy Phase I	Recruiting
NCT04300244	NIPU (UV1 Vaccine + Nivo/Ipi)	Cancer Vaccine Phase II	Enrollment complete; Phase III planning
NCT06057935	ICARuS II (HIPEC for Peritoneal)	Surgical Phase II	Recruiting
NCT07253662	PIPAC with Nab-Paclitaxel	Surgical Phase I/II	Recruiting
NCT07133750	BNT327/PM8002 Phase III	Bispecific Antibody Phase III	Registered July 2025
NCT02899299	CheckMate 743 (Nivo + Ipi)	Immunotherapy Phase III	Enrollment complete; 5-year data published Feb 2026
NCT02784171	KEYNOTE-483 / IND.227	Immunotherapy Phase II/III	FDA-approved September 2024
NCT02397928	STELLAR (TTFields)	Device Phase II	Completed; HDE approved May 2019
NCT06477419	Sacituzumab Govitecan (TROP-2 ADC)	ADC Phase II	Recruiting
NCT04981119	BASECAMP-1 (EVEREST-2 Prescreening)	Prescreening Registry	Recruiting

"Pursuing a mesothelioma lawsuit does not affect your eligibility for clinical trials. In fact, the compensation our clients receive often helps cover travel costs and other expenses associated with trial participation. We believe patients deserve access to the best treatments available while also holding the companies responsible for their asbestos exposure accountable."

— Paul Danziger, Founding Partner, Danziger & De Llano

Related Resources

• Mesothelioma_Treatment_Options — Comprehensive overview of all treatment approaches
• Immunotherapy_for_Mesothelioma — Detailed coverage of CheckMate 743, KEYNOTE-483, and emerging immunotherapy combinations
• Stage_3_Mesothelioma — Staging, prognosis, and treatment options for locally advanced disease
• Peritoneal_Mesothelioma — Diagnosis, CRS-HIPEC, and peritoneal-specific trial options
• Survival_Statistics — Survival rates by stage, histology, and treatment modality
• Mesothelioma_Diagnosis_and_Staging — TNM staging, diagnostic workup, and biomarker testing
• Mesothelioma Lawyers Near Me Blog — Latest articles on treatment, legal rights, and patient resources
• Mesothelioma.net — Comprehensive mesothelioma information and support resources