CheckMate 743 Trial
Executive Summary
The CheckMate 743 trial represents the most significant breakthrough in mesothelioma treatment since the approval of chemotherapy in 2004. This phase 3 randomized study[1], led by Dr. Paul Baas at the Netherlands Cancer Institute, enrolled 605 patients across 21 countries and demonstrated that first-line treatment with nivolumab plus ipilimumab (immunotherapy) significantly improved survival compared to standard chemotherapy. Patients receiving immunotherapy achieved median overall survival of 18.1 months versus 14.1 months with chemotherapy—a 26% reduction in death risk (hazard ratio 0.74).[2] These results led directly to FDA approval on October 2, 2020[3], establishing dual immunotherapy as the new global standard of care for unresectable malignant pleural mesothelioma[4].[5]
At a Glance
| Item | Detail |
|---|---|
| Trial Name | CheckMate 743 (NCT02899299) |
| Disease | Unresectable malignant pleural mesothelioma (first-line) |
| Treatment Tested | Nivolumab (Opdivo) + ipilimumab (Yervoy) vs. platinum-based chemotherapy |
| Patients Enrolled | 605 across 21 countries |
| Median Overall Survival | 18.1 months (immunotherapy) vs. 14.1 months (chemotherapy) |
| 5-Year Overall Survival (JCO 2026) | 14% (immunotherapy) vs. 6% (chemotherapy); HR 0.74 |
| Non-Epithelioid 5-Year OS | 12% vs. 1%; HR 0.48 |
| FDA Approval | October 2, 2020 |
| Lead Investigator | Dr. Paul Baas, Netherlands Cancer Institute |
| Initial Publication | The Lancet, January 2021 |
| 5-Year Follow-Up Publication | Journal of Clinical Oncology, February 2026 |
Key Facts
| Key Facts: CheckMate 743 Trial Results |
|---|
|
What Was the CheckMate 743 Trial and Why Did It Matter?
CheckMate 743 was an open-label, phase 3, randomized clinical trial designed to determine whether dual immune checkpoint inhibitor therapy[6] could improve survival in patients with malignant pleural mesothelioma compared to standard platinum-based chemotherapy.
Before this trial, mesothelioma patients had essentially one first-line treatment option: pemetrexed combined with cisplatin or carboplatin. This chemotherapy regimen had been the standard of care since FDA approval in 2004—a span of 16 years without any significant treatment advances.[7]
| ℹ️ Why "CheckMate"? Bristol-Myers Squibb's immunotherapy clinical trial program uses the "CheckMate" naming convention. The number 743 simply identifies this specific trial within their research portfolio. The name has become synonymous with the mesothelioma immunotherapy breakthrough. |
The trial was led by Dr. Paul Baas, a Dutch thoracic oncologist at the Netherlands Cancer Institute who had spent decades working to improve mesothelioma treatment. His international team included researchers from the United States, France, Australia, the United Kingdom, and other countries.[8]
"For 16 years, we could only offer our newly diagnosed clients one treatment option. CheckMate 743 changed everything. Now when we meet with mesothelioma patients, we can discuss immunotherapy — a treatment proven to extend survival and give families precious additional time together."
<footer style="text-align:right; padding-top:0.5em;">— Paul Danziger, Attorney, Founding Partner, Danziger & De Llano</footer>
How Was the CheckMate 743 Trial Designed?
The trial's rigorous design ensured that its results would be scientifically valid and applicable to real-world mesothelioma patients.[9]
Patient Eligibility
To enroll in CheckMate 743, patients had to meet specific criteria:
- Confirmed diagnosis of unresectable malignant pleural mesothelioma (any histologic subtype)
- No prior systemic therapy for mesothelioma
- Adequate organ function
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Treatment Arms
| Arm | Treatment | Schedule |
|---|---|---|
| Immunotherapy | Nivolumab 3 mg/kg IV + Ipilimumab 1 mg/kg IV | Nivolumab every 2 weeks; Ipilimumab every 6 weeks; continued until progression or toxicity |
| Chemotherapy | Pemetrexed 500 mg/m² IV + Cisplatin 75 mg/m² (or Carboplatin AUC 5) IV | Every 3 weeks for up to 6 cycles |
The trial randomized patients 1:1 to either treatment arm. The primary endpoint was overall survival—the gold standard for cancer clinical trials.[10]
What Were the Key Results of CheckMate 743?
The results, published in The Lancet[11] in January 2021, demonstrated clear superiority for the immunotherapy combination across multiple measures.
Primary Endpoint: Overall Survival
| Outcome | Immunotherapy | Chemotherapy | Difference |
|---|---|---|---|
| Median Overall Survival | 18.1 months | 14.1 months | +4 months |
| Two-Year Survival Rate | 41% | 27% | +14% |
| Hazard Ratio for Death | 0.74 (95% CI: 0.61-0.89; p=0.002) | ||
The hazard ratio of 0.74 means that patients receiving immunotherapy had a 26% lower risk of death at any given time point compared to those receiving chemotherapy.[12]
Results by Histologic Subtype
Perhaps the most dramatic finding was the differential benefit based on mesothelioma cell type:
| ✅ Breakthrough for Non-Epithelioid Patients: Patients with non-epithelioid mesothelioma (sarcomatoid and biphasic subtypes) historically had the worst prognosis. In CheckMate 743, these patients saw their median survival more than double—from 8.8 months with chemotherapy to 18.1 months with immunotherapy. |
| Subtype | Immunotherapy Survival | Chemotherapy Survival | Improvement |
|---|---|---|---|
| Epithelioid | 18.7 months | 16.5 months | +2.2 months |
| Non-Epithelioid | 18.1 months | 8.8 months | +9.3 months (doubled) |
This finding was particularly significant because non-epithelioid mesothelioma had long been considered nearly untreatable.[13]
Five-Year Follow-Up: The 2026 Update
In February 2026, the CheckMate 743 investigators published five-year follow-up results in the Journal of Clinical Oncology — the longest reported follow-up for first-line immunotherapy in pleural mesothelioma.[14] At a median follow-up of 66.8 months, the survival advantage seen at the initial readout had not only held — it had widened.
| ✅ Five-Year Survival More Than Doubled. At five years, 14% of patients on nivolumab plus ipilimumab were still alive, compared to 6% on chemotherapy — a clinically meaningful long-term survival benefit in a disease where five-year survival had historically been under 10%. |
Five-Year Overall Survival
| Patient Group | Nivolumab + Ipilimumab | Chemotherapy | Hazard Ratio (95% CI) |
|---|---|---|---|
| All patients (5-year OS) | 14% | 6% | 0.74 (0.62–0.88) |
| Epithelioid subtype (5-year OS) | 14% | 8% | 0.85 (0.69–1.03) |
| Non-epithelioid subtype (5-year OS) | 12% | 1% | 0.48 (0.33–0.68) |
The non-epithelioid finding — 12% alive at five years on immunotherapy versus 1% on chemotherapy — firmly establishes nivolumab plus ipilimumab as the standard of care for sarcomatoid and biphasic pleural mesothelioma, subtypes that have historically been treatment-resistant and carried the shortest survival.[15]
Treatment-Switching Adjustment
A substantial proportion of patients originally assigned to chemotherapy went on to receive immunotherapy after disease progression. The investigators performed a treatment-switching adjustment to estimate what the chemotherapy arm's survival would have looked like had no patients crossed over. After this adjustment, the overall survival hazard ratio favoring nivolumab plus ipilimumab strengthened to 0.64 (95% CI: 0.53–0.78) — meaning the true survival benefit of first-line immunotherapy is likely even larger than the unadjusted analysis suggests.[16]
A New Biomarker: M-MDSC Levels
The 2026 update also reported a biomarker finding with implications for patient selection. Baseline levels of monocytic myeloid-derived suppressor cells (M-MDSCs) — a population of immune cells that suppress anti-tumor T-cell activity — were associated with overall survival on immunotherapy. High baseline M-MDSC levels correlated with significantly worse outcomes (hazard ratio 1.25), suggesting that this circulating immune cell population may help identify patients least likely to benefit from checkpoint inhibition and most in need of alternative or combination strategies.[17] Validation in additional cohorts is needed before M-MDSC testing enters routine practice.
Safety Profile at Five Years
No new safety signals emerged with extended follow-up. The pattern of immune-related adverse events seen in the initial analysis — predominantly skin, endocrine, and gastrointestinal toxicities, manageable with established protocols — was consistent across the longer observation period. The five-year safety data support the durability of the treatment's risk-benefit profile.[18]
How Did CheckMate 743 Lead to FDA Approval?
Based on the strength of the trial results, the FDA approved the combination of nivolumab plus ipilimumab on October 2, 2020—even before the full results were published in The Lancet.[19]
| Milestone | Date | Significance |
|---|---|---|
| Trial Enrollment Completed | 2018 | 605 patients enrolled |
| Interim Analysis Positive | 2020 | Primary endpoint met |
| FDA Approval | October 2, 2020 | First new mesothelioma drug in 16 years |
| The Lancet Publication | January 2021 | Full results published |
| EMA Approval | 2021 | European approval followed |
This approval established dual immune checkpoint inhibitor therapy as the new global standard of care for previously untreated unresectable malignant pleural mesothelioma.[20]
"The FDA approval based on CheckMate 743 was a watershed moment. For the first time in 16 years, mesothelioma patients had a new treatment option — one that offered significantly better outcomes, especially for those with non-epithelioid disease who previously had so few options."
<footer style="text-align:right; padding-top:0.5em;">— Rod De Llano, Attorney, Founding Partner, Danziger & De Llano</footer>
How Does the Immunotherapy Combination Work?
Nivolumab and ipilimumab work by different but complementary mechanisms to help the immune system recognize and attack mesothelioma cells.[21]
Nivolumab (Opdivo)
Nivolumab is a PD-1 inhibitor. Cancer cells often express a protein called PD-L1 that binds to PD-1 on immune cells, essentially telling the immune system to "stand down" and not attack. Nivolumab blocks this interaction, allowing immune cells to recognize and destroy cancer cells.[22]
Ipilimumab (Yervoy)
Ipilimumab is a CTLA-4 inhibitor. CTLA-4 is another "checkpoint" that normally limits immune cell activation. By blocking CTLA-4, ipilimumab enhances the immune system's ability to mount a sustained attack against cancer cells.[23]
Why Dual Checkpoint Inhibition?
The combination of these two drugs produces better results than either alone because they target different points in the immune response:
- Ipilimumab activates immune cells at an early stage, priming them to attack
- Nivolumab removes the "brakes" that cancer cells use to hide from activated immune cells
This dual mechanism creates a more comprehensive anti-tumor immune response.[24]
Who Is Eligible for Immunotherapy Based on CheckMate 743?
The FDA approved nivolumab plus ipilimumab for adult patients with unresectable malignant pleural mesothelioma who have not received prior systemic therapy.[25]
Appropriate Candidates:
- Diagnosis of malignant pleural mesothelioma (any histologic subtype)
- Disease that cannot be surgically removed (unresectable)
- No prior chemotherapy or immunotherapy for mesothelioma
- Adequate organ function
- Ability to tolerate treatment side effects
| ⚠️ Important Consideration: While immunotherapy is now a first-line option, the choice between immunotherapy and chemotherapy should be made in consultation with an experienced oncologist. Some patients may benefit more from chemotherapy, particularly those who need rapid tumor response. |
What Side Effects Were Observed in CheckMate 743?
Like all cancer treatments, the immunotherapy combination can cause side effects. In CheckMate 743, the most common treatment-related adverse events included:[26]
| Side Effect | Immunotherapy | Chemotherapy |
|---|---|---|
| Diarrhea | 26% | 35% |
| Fatigue | 24% | 25% |
| Pruritus (itching) | 21% | 4% |
| Rash | 21% | 5% |
| Nausea | 17% | 51% |
Importantly, serious side effects (grade 3-4) occurred at similar rates between the two treatment arms. Immunotherapy side effects are generally immune-related and can usually be managed with appropriate medical care.[27]
What Does CheckMate 743 Mean for Mesothelioma Patients Today?
The approval of nivolumab plus ipilimumab based on CheckMate 743 has fundamentally changed the treatment landscape for mesothelioma patients.[28]
For Newly Diagnosed Patients:
- A proven first-line treatment option beyond chemotherapy
- Particularly important for non-epithelioid subtypes
- Available at major mesothelioma treatment centers
- Covered by most insurance plans
For the Field of Mesothelioma Research:
- Validated immunotherapy as effective against mesothelioma
- Opened doors for additional immunotherapy research
- Led to trials of immunotherapy in earlier disease stages
- Sparked investigation of immunotherapy combinations with surgery
"CheckMate 743 gave our clients something they desperately needed: hope. When we walk newly diagnosed patients through their options now, we have something we did not have for 16 years — a proven combination therapy approved on the strength of a landmark trial. That shifts the emotional weight of the first conversation from despair to possibility."
<footer style="text-align:right; padding-top:0.5em;">— David Foster, Director of Client Services, Danziger & De Llano</footer>
See Also
- Dr. Paul Baas (Lead Investigator)
- History of Mesothelioma Research
- Clinical Trials
- Treatment Options
- Immunotherapy
- Mesothelioma Treatment Centers
References
- ↑ CheckMate 743 Trial (NCT02899299), ClinicalTrials.gov
- ↑ Immunotherapy for Mesothelioma, Mesothelioma.net
- ↑ FDA Approves Nivolumab and Ipilimumab for Mesothelioma, U.S. Food and Drug Administration
- ↑ Cancer Stat Facts: Mesothelioma, NCI SEER Program
- ↑ First New Approved Treatment for Mesothelioma, Mesothelioma Lawyer Center
- ↑ Immunotherapy to Treat Cancer, National Cancer Institute
- ↑ Mesothelioma Treatment, Mesothelioma.net
- ↑ Mesothelioma: Diagnosis, Treatment & Legal Help, Mesothelioma Lawyer Center
- ↑ CheckMate 743 Study Record (NCT02899299), ClinicalTrials.gov.
- ↑ Clinical Trials for Mesothelioma Treatment, Mesothelioma.net
- ↑ Baas P, Scherpereel A, Nowak AK, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397(10272):375-386. PubMed PMID: 33485464.
- ↑ First New Approved Treatment for Mesothelioma, Mesothelioma Lawyer Center
- ↑ Sarcomatoid Mesothelioma, Mesothelioma.net
- ↑ Scherpereel A, Baas P, Nowak AK, et al. Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743. J Clin Oncol. 2026;44(9):742-749. PubMed PMID: 41734361.
- ↑ Five-Year Outcomes With First-Line Nivolumab Plus Ipilimumab in Unresectable Pleural Mesothelioma, The ASCO Post, March 2026.
- ↑ Scherpereel A, et al. J Clin Oncol. 2026;44(9):742-749. PubMed PMID: 41734361.
- ↑ Scherpereel A, et al. J Clin Oncol. 2026;44(9):742-749. PubMed PMID: 41734361.
- ↑ First New Approved Treatment for Mesothelioma, Mesothelioma Lawyer Center.
- ↑ FDA Approves Nivolumab and Ipilimumab for Unresectable Malignant Pleural Mesothelioma, U.S. Food and Drug Administration, October 2, 2020.
- ↑ Benefits of Immunotherapy Match Those of Chemotherapy, Mesothelioma Lawyer Center
- ↑ Immunotherapy for Mesothelioma, Mesothelioma.net
- ↑ Nivolumab — NCI Drug Dictionary, National Cancer Institute.
- ↑ New Mesothelioma Treatments, MesotheliomaAttorney.com
- ↑ New Mesothelioma Treatments and Research, Mesothelioma.net
- ↑ FDA Approves Nivolumab and Ipilimumab for Unresectable Malignant Pleural Mesothelioma, U.S. Food and Drug Administration, October 2, 2020.
- ↑ Mesothelioma Treatment, Mesothelioma.net
- ↑ Asbestos Cancer, Mesothelioma Lawyer Center
- ↑ Scherpereel A, Baas P, Nowak AK, et al. Five-Year Clinical Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Unresectable Pleural Mesothelioma in CheckMate 743. J Clin Oncol. 2026;44(9):742-749. PubMed PMID: 41734361.