CheckMate 743
Needs reviewFirst-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial
Phase 3N = 605NCT02899299
- Population
- Adults aged 18 years and older with previously untreated, histologically confirmed unresectable malignant pleural mesothelioma and ECOG performance status 0 or 1
- Design
- Open-label randomised phase 3 trial at 103 hospitals in 21 countries; 713 patients were enrolled between 29 November 2016 and 28 April 2018 and 605 were randomly assigned 1:1. The primary endpoint was overall survival among all participants randomly assigned. The experimental arm contained no chemotherapy. Updates were reported at 3 years' minimum follow-up and at 5 years. The registry record lists an enrolment of 605.
- Primary endpoint
- OS
- Arms
- Nivolumab plus ipilimumab (experimental, n = 303): Nivolumab 3 mg/kg intravenously every 2 weeks plus ipilimumab 1 mg/kg intravenously every 6 weeks for up to 2 years
- Platinum plus pemetrexed (control, n = 302): Pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin AUC 5 mg/mL per min intravenously once every 3 weeks for up to six cycles
- People
- Baas P
OSHR 0.74Δ median OS+4 monthsΔ 24-month OS+14 pointsOSHR 0.74 (95% CI 0.61–0.89)Δ median OS+4 monthsPFSHR 1.00 (95% CI 0.82–1.21)
Show the numbers
| Endpoint | Analysis | Nivolumab plus ipilimumab | Platinum plus pemetrexed | Effect |
|---|---|---|---|---|
| OSAll randomised patients | interimmedian follow-up 29.7 monthsBaas 2021 | median 18.1 months (16.8–21.4); 41% at 2 y (35.1–46.5%) | median 14.1 months (12.4–16.2); 27% at 2 y (21.9–32.4%) | HR 0.74P=0.0020Prespecified interim analysis (database lock 3 April 2020). The hazard ratio is reported with a 96.6% CI of 0.60 to 0.91, not a 95% CI. |
| OSAll randomised patients (FDA labelling analysis of the prespecified interim analysis) | interimSource 2020 | median 18.1 months (16.8–21.5) | median 14.1 months (12.5–16.2) | HR 0.74 (95% CI 0.61–0.89)P=0.002Stratified log-rank p-value. At the time of the interim analysis 419 deaths (89% of the deaths needed for the final analysis) had occurred, per the label. |
| PFSAll randomised patients (FDA labelling analysis of the prespecified interim analysis)Progression-free survival assessed by blinded independent central review using modified RECIST (label wording) | interimSource 2020 | median 6.8 months (5.6–7.4) | median 7.2 months (6.9–8.1) | HR 1.00 (95% CI 0.82–1.21)Reported in the FDA label table; the Lancet abstract gives no progression-free survival result. The label prints no p-value for progression-free survival. |
| ORRAll randomised patients (FDA labelling analysis of the prespecified interim analysis)Overall response rate assessed by blinded independent central review using modified RECIST (label wording) | interimSource 2020 | 40% (34–45%) | 43% (37–49%) | Response rates as printed in the label, rounded to whole percentages. The same table gives median duration of response 11.0 months (95% CI 8.1 to 16.5) with nivolumab plus ipilimumab and 6.7 months (5.3 to 7.1) with chemotherapy. |
| OSAll randomised patients | long term-updatemedian follow-up 43.1 monthsPeters 2022 | median 18.1 months; 23% at 3 y | median 14.1 months; 15% at 3 y | HR 0.73 (95% CI 0.61–0.87)Update with 3 years' minimum follow-up (Annals of Oncology 2022). The abstract gives no confidence intervals for the medians or the 3-year rates. |
| PFSAll randomised patients | long term-updatemedian follow-up 43.1 monthsPeters 2022 | 14% at 3 y | 1% at 3 y | Three-year progression-free survival rates as stated in the abstract, which gives no median progression-free survival or hazard ratio. |
| OSAll randomised patients | long term-updatemedian follow-up 66.8 monthsScherpereel 2026 | 14% at 5 y | 6% at 5 y | HR 0.74 (95% CI 0.62–0.88)Five-year report (J Clin Oncol 2026). The abstract and the Results text give 5-year rates and the hazard ratio but no medians or intervals for the rates. Two errata to this report have been published (J Clin Oncol 2026;44(19):1852 and 2026;44(29):2878); their content could not be read, so these values are as printed in the original report and may differ from the corrected version. |
| OSAll randomised patients, adjusted for subsequent immunotherapy in the chemotherapy armOverall survival adjusted for subsequent immunotherapy in the chemotherapy arm (treatment-switching analysis) | exploratorymedian follow-up 66.8 monthsScherpereel 2026 | — | — | HR 0.64 (95% CI 0.53–0.78)24% of patients in the chemotherapy arm received subsequent immunotherapy (abstract; 72 patients in the Results text). The abstract does not describe the adjustment method; the Results text names inverse probability of censoring weighting. Two errata to this report have been published (J Clin Oncol 2026;44(19):1852 and 2026;44(29):2878); their content could not be read, so these values are as printed in the original report and may differ from the corrected version. |
| Endpoint | Analysis | Nivolumab plus ipilimumab | Platinum plus pemetrexed | Effect |
|---|---|---|---|---|
| OSAll randomised patients | interimmedian follow-up 29.7 monthsBaas 2021 | median 18.1 months (16.8–21.4); 41% at 2 y (35.1–46.5%) | median 14.1 months (12.4–16.2); 27% at 2 y (21.9–32.4%) | HR 0.74P=0.0020Prespecified interim analysis (database lock 3 April 2020). The hazard ratio is reported with a 96.6% CI of 0.60 to 0.91, not a 95% CI. |
| OSAll randomised patients (FDA labelling analysis of the prespecified interim analysis) | interimSource 2020 | median 18.1 months (16.8–21.5) | median 14.1 months (12.5–16.2) | HR 0.74 (95% CI 0.61–0.89)P=0.002Stratified log-rank p-value. At the time of the interim analysis 419 deaths (89% of the deaths needed for the final analysis) had occurred, per the label. |
| PFSAll randomised patients (FDA labelling analysis of the prespecified interim analysis)Progression-free survival assessed by blinded independent central review using modified RECIST (label wording) | interimSource 2020 | median 6.8 months (5.6–7.4) | median 7.2 months (6.9–8.1) | HR 1.00 (95% CI 0.82–1.21)Reported in the FDA label table; the Lancet abstract gives no progression-free survival result. The label prints no p-value for progression-free survival. |
| ORRAll randomised patients (FDA labelling analysis of the prespecified interim analysis)Overall response rate assessed by blinded independent central review using modified RECIST (label wording) | interimSource 2020 | 40% (34–45%) | 43% (37–49%) | Response rates as printed in the label, rounded to whole percentages. The same table gives median duration of response 11.0 months (95% CI 8.1 to 16.5) with nivolumab plus ipilimumab and 6.7 months (5.3 to 7.1) with chemotherapy. |
| OSAll randomised patients | long term-updatemedian follow-up 43.1 monthsPeters 2022 | median 18.1 months; 23% at 3 y | median 14.1 months; 15% at 3 y | HR 0.73 (95% CI 0.61–0.87)Update with 3 years' minimum follow-up (Annals of Oncology 2022). The abstract gives no confidence intervals for the medians or the 3-year rates. |
| PFSAll randomised patients | long term-updatemedian follow-up 43.1 monthsPeters 2022 | 14% at 3 y | 1% at 3 y | Three-year progression-free survival rates as stated in the abstract, which gives no median progression-free survival or hazard ratio. |
| OSAll randomised patients | long term-updatemedian follow-up 66.8 monthsScherpereel 2026 | 14% at 5 y | 6% at 5 y | HR 0.74 (95% CI 0.62–0.88)Five-year report (J Clin Oncol 2026). The abstract and the Results text give 5-year rates and the hazard ratio but no medians or intervals for the rates. Two errata to this report have been published (J Clin Oncol 2026;44(19):1852 and 2026;44(29):2878); their content could not be read, so these values are as printed in the original report and may differ from the corrected version. |
| OSAll randomised patients, adjusted for subsequent immunotherapy in the chemotherapy armOverall survival adjusted for subsequent immunotherapy in the chemotherapy arm (treatment-switching analysis) | exploratorymedian follow-up 66.8 monthsScherpereel 2026 | — | — | HR 0.64 (95% CI 0.53–0.78)24% of patients in the chemotherapy arm received subsequent immunotherapy (abstract; 72 patients in the Results text). The abstract does not describe the adjustment method; the Results text names inverse probability of censoring weighting. Two errata to this report have been published (J Clin Oncol 2026;44(19):1852 and 2026;44(29):2878); their content could not be read, so these values are as printed in the original report and may differ from the corrected version. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.74 | 0.61–0.89 |
| PFS | 1 | 0.82–1.21 |
| OS | 0.73 | 0.61–0.87 |
| OS | 0.74 | 0.62–0.88 |
| OS | 0.64 | 0.53–0.78 |
- Nivolumab plus ipilimumab (experimental)
- Platinum plus pemetrexed (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Nivolumab plus ipilimumab | Platinum plus pemetrexed |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 11 | 65.6% | 58.2% |
| 23 | 41.4% | 32.3% |
| 34 | 27.2% | 18.8% |
| 45 | 17.8% | 10.9% |
- Nivolumab plus ipilimumab (experimental)
- Platinum plus pemetrexed (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Nivolumab plus ipilimumab | Platinum plus pemetrexed |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 11 | 65.6% | 58.2% |
| 23 | 41.4% | 32.3% |
| 34 | 27.2% | 18.8% |
| 45 | 17.8% | 10.9% |
Appears in
Sources
Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, 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.
U.S. Food and Drug Administration. OPDIVO (nivolumab) prescribing information enclosed with the BLA 125554/S-089 approval letter (Reference ID 4679692). Section 14.5: malignant pleural mesothelioma, CHECKMATE-743.
Peters S, Scherpereel A, Cornelissen R, Oulkhouir Y, Greillier L, Kaplan MA, et al. First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Ann Oncol. 2022;33(5):488-499.
Scherpereel A, Baas P, Nowak AK, Tsao AS, Fujimoto N, Peters S, 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.