CheckMate-743: Immunotherapy Beats Chemo
CheckMate-743 trial shows nivolumab plus ipilimumab extends median survival to 18.1 months vs 14.1 months with chemotherapy. 3-year survival doubles.
Five-year update available: The CheckMate-743 five-year survival data, published February 26, 2026, in the Journal of Clinical Oncology, shows 14% five-year survival with immunotherapy versus 6% with chemotherapy.
Trial Results Show Significant Survival Benefit
The CheckMate-743 trial has demonstrated that combining two immunotherapy drugs, nivolumab (Opdivo) and ipilimumab (Yervoy), significantly extends survival for patients with unresectable malignant pleural mesothelioma compared to standard chemotherapy.
This Phase 3, multicenter, randomized trial represents the first immunotherapy regimen to show superior survival over chemotherapy in mesothelioma, potentially changing the standard of care for the first time in nearly two decades.
Key Survival Data
| Outcome | Immunotherapy | Chemotherapy |
|---|---|---|
| Median overall survival | 18.1 months | 14.1 months |
| 2-year survival rate | 41% | 27% |
| 3-year survival rate | 23% | 15% |
| Objective response rate | 40% | 43% |
The trial showed a hazard ratio of 0.74 (p=0.002), representing a 26% reduction in the risk of death with the immunotherapy combination.
What This Means for Patients
The results are particularly significant for three reasons. Three-year survival rates were nearly double (23% versus 15%), meaning more patients live longer with immunotherapy. Pemetrexed plus platinum chemotherapy had been the standard since 2004, and CheckMate-743 was the first regimen to demonstrate superior survival in nearly two decades. The responses also proved durable: 38% of patients achieved partial tumor shrinkage, with some responses lasting over a year.
How the Treatment Works
The combination targets two different immune checkpoints. Nivolumab blocks PD-1, a protein that cancer cells use to hide from the immune system, so blocking PD-1 lets T-cells recognize and attack mesothelioma cells. Ipilimumab blocks CTLA-4, which normally limits T-cell activation, so blocking CTLA-4 allows more T-cells to be primed and expanded to target cancer cells.
Together, the drugs produce a stronger immune response than either alone.
Treatment Schedule
- Nivolumab: 360 mg every 3 weeks
- Ipilimumab: 1 mg/kg every 6 weeks
- Duration: Up to 2 years or until disease progression
Who Was Studied
The trial enrolled 605 patients with:
- Previously untreated unresectable malignant pleural mesothelioma
- All histological subtypes (epithelioid, sarcomatoid, biphasic)
- Good performance status (ECOG 0-1)
Patients were randomized to receive either nivolumab plus ipilimumab or standard chemotherapy (pemetrexed plus cisplatin or carboplatin).
Benefit Across Subtypes
The immunotherapy combination showed benefit regardless of histological subtype:
| Subtype | Immunotherapy Median OS | Chemotherapy Median OS |
|---|---|---|
| Epithelioid | 18.7 months | 16.5 months |
| Non-epithelioid | 18.1 months | 8.8 months |
The benefit was particularly striking in non-epithelioid (sarcomatoid/biphasic) disease, where chemotherapy historically performs poorly. These patients more than doubled their median survival with immunotherapy.
CheckMate-743 is the first trial to show superior survival over chemotherapy in mesothelioma, changing the standard of care for the first time in nearly two decades.
Side Effects
Immune-related adverse events occurred in approximately 30% of patients receiving immunotherapy. The most common included:
- Rash
- Diarrhea/colitis
- Thyroid dysfunction
- Hepatitis
- Pneumonitis
Most immune-related side effects were manageable with steroids or other immunosuppressive treatments. Treatment-related deaths occurred in 1.5% of immunotherapy patients vs 0.3% with chemotherapy.
Path to FDA Approval
Based on these results, the FDA granted approval to nivolumab plus ipilimumab as first-line treatment for unresectable malignant pleural mesothelioma on October 2, 2020.
This makes it the first immunotherapy approved specifically for mesothelioma.
What Patients Should Know
- The combination is approved for unresectable (cannot be surgically removed) pleural mesothelioma
- It is a first-line treatment, meaning it can be used before trying chemotherapy
- Not all patients respond, discuss with your oncologist whether immunotherapy is right for you
- Treatment is given intravenously at a cancer center
- Side effects differ from chemotherapy and require specialized management
Clinical Significance
Dr. Paul Baas, lead investigator of the primary Lancet publication, noted that this trial “provides a new first-line treatment option for patients with malignant pleural mesothelioma.” The results confirm that immunotherapy can fundamentally change outcomes in this historically difficult-to-treat cancer.
Reader Q&A
Frequently Asked Questions
Who is eligible for nivolumab plus ipilimumab?
The combination is FDA-approved for unresectable (cannot be surgically removed) malignant pleural mesothelioma. It’s a first-line treatment, meaning it can be used before trying chemotherapy.
Why is this trial important for non-epithelioid mesothelioma?
Non-epithelioid patients (sarcomatoid, biphasic) historically had poor chemotherapy response. These patients more than doubled their survival with immunotherapy (18.1 vs 8.8 months).
How long is treatment given?
Treatment continues for up to 2 years or until disease progression. Nivolumab is given every 3 weeks; ipilimumab every 6 weeks.
What are the main side effects?
Immune-related side effects occur in ~30% of patients, including rash, diarrhea, thyroid dysfunction, and hepatitis. Most are manageable with steroids or other treatments.
What is the success rate of nivolumab and ipilimumab?
The success of nivolumab and ipilimumab depends on how success is measured and the cancer type being treated. In advanced melanoma, the CheckMate-067 trial showed that after 10 years, the combination of nivolumab plus ipilimumab achieved a 43% overall survival rate, compared to 37% with nivolumab alone and 19% with ipilimumab alone. Median overall survival with the combination was 71.9 months versus 36.9 months with nivolumab monotherapy. Melanoma-specific survival at 10 years was 52% with the combination, 44% with nivolumab alone, and 23% with ipilimumab alone. Response rates were also higher with the combination, with 87% of patients achieving tumor burden reduction of 80% or greater. Outcomes vary by cancer type, PD-L1 expression levels, and individual patient factors, so people with cancer should discuss specific survival data relevant to their diagnosis with their trial lawyer or oncology team.
Do you lose your hair with nivolumab?
Hair loss with nivolumab (Opdivo) is uncommon, occurring in fewer than 1-2% of people receiving the drug. When hair loss does occur, it typically manifests as gradual thinning rather than complete baldness, and hair usually returns to normal after treatment ends. In rare cases, nivolumab can trigger alopecia areata, an immune-related adverse event where the immune system mistakenly attacks hair follicles, causing patchy hair loss that may appear 2 to 15 months after starting treatment. Hair loss may also result from combination therapy with chemotherapy drugs or from nivolumab lowering thyroid hormone levels, which can be managed with thyroid medication. People experiencing hair loss during nivolumab treatment can discuss management options, including topical or intralesional corticosteroids, with their care team.
Why only 4 doses of ipilimumab?
The standard regimen of ipilimumab for unresectable or metastatic melanoma is 3 mg/kg intravenously every 3 weeks for 4 doses, based on phase III trials like MDX010-20 and CA184-024 that established its superiority over alternatives like gp100 vaccine or dacarbazine. This 4-dose induction derived from monotherapy experience, where higher doses like 10 mg/kg improved survival but doubled toxicity, yet no prior studies tested fewer than 4 doses in combinations. Emerging data from trials like ADAPT-IT and CheckMate 067 show efficacy and toxicity often driven by the first 1-2 doses of ipilimumab plus nivolumab, with 75% of patients in one study receiving only 1-2 doses and responses observed after a single dose, though durability with fewer doses remains unclear. Lower or alternative schedules (e.g., 1 mg/kg or 50 mg every 6 weeks) may reduce grade 3/4 adverse events while preserving efficacy in PD-1 combinations. Therapy is withheld for moderate reactions and permanently discontinued if unresolved or if the course exceeds 16 weeks.
Which cancers are most successfully treated with immunotherapy?
Immunotherapy has shown the strongest clinical outcomes in melanoma, non-small cell lung cancer, colorectal cancer with microsatellite instability (MSI-H), and certain blood cancers. In melanoma, 20-40% of people with advanced disease achieve durable long-term responses, while CAR T-cell therapy has achieved remission in up to 90% of children and young adults with specific leukemias. For colorectal cancer with MSI-H mutations, pembrolizumab produced 98% one-year survival and 84% three-year survival rates in clinical trials. Checkpoint inhibitors have also extended survival in bladder cancer, gastric cancer, and cervical cancer, with over 40 immunotherapy drugs now approved across more than 30 cancer types. Response rates vary significantly by cancer type and individual tumor characteristics, making biomarker testing important for treatment selection.