CheckMate 743 Trial

CheckMate 743 Trial
Landmark Mesothelioma Immunotherapy Study
Trial Type	Phase 3, Randomized
Patients	605
Countries	21
Lead Investigator	Dr. Paul Baas
FDA Approval	October 2, 2020
Survival Benefit	18.1 vs 14.1 months
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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, 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). These results led directly to FDA approval on October 2, 2020, establishing dual immunotherapy as the new global standard of care for unresectable malignant pleural mesothelioma.

Key Facts

Key Facts: CheckMate 743 Trial Results

Enrollment: 605 patients with previously untreated unresectable malignant pleural mesothelioma Countries: 21 nations participated in the global trial Randomization: 1:1 ratio to immunotherapy or chemotherapy Treatment Arm: Nivolumab (Opdivo) 3 mg/kg every 2 weeks + Ipilimumab (Yervoy) 1 mg/kg every 6 weeks Control Arm: Pemetrexed + cisplatin or carboplatin (standard chemotherapy) Median Survival (Immunotherapy): 18.1 months Median Survival (Chemotherapy): 14.1 months Hazard Ratio: 0.74 (26% reduction in death risk) Two-Year Survival: 41% immunotherapy vs 27% chemotherapy Non-Epithelioid Benefit: Survival doubled from 8.8 to 18.1 months FDA Approval Date: October 2, 2020 Publication: The Lancet, January 2021

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 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.

Info: 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.

"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."

— Paul Danziger, Founding Partner, Danziger & De Llano

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.

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.

What Were the Key Results of CheckMate 743?

The results, published in The Lancet 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.

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.

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.

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.

"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."

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

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.

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.

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.

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.

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.

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:

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.

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.

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 tell newly diagnosed patients that there are now two proven treatment options—and that immunotherapy can more than double survival for some—we're sharing the results of this landmark trial. It changes the conversation from despair to possibility."

— David Foster, Client Advocate, Danziger & De Llano

Get Help Today

If you or a loved one has been diagnosed with mesothelioma, accessing the latest treatments—including the immunotherapy validated by CheckMate 743—is critical. You may also be entitled to significant compensation from the companies responsible for your asbestos exposure.

The experienced mesothelioma attorneys at Danziger & De Llano have helped thousands of families navigate both the medical and legal challenges of this diagnosis.

For veterans with mesothelioma, the VA provides specialized benefits and healthcare services.

Call (866) 222-9990 or request a free case review online.

See Also

• Dr. Paul Baas (Lead Investigator)
• History of Mesothelioma Research
• Clinical Trials
• Treatment Options
• Immunotherapy
• Mesothelioma Treatment Centers