CheckMate 649
Efficacy Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Against Chemotherapy in Stomach Cancer or Stomach/Esophagus Junction Cancer
Phase 3N = 1,581NCT02872116
- Population
- Previously untreated, unresectable, non-HER2-positive gastric, gastro-oesophageal junction or oesophageal adenocarcinoma, regardless of PD-L1 expression (about 70% gastric by primary tumour location in the 3-year report).
- Design
- Multicentre open-label randomised phase 3 trial in 175 hospitals and cancer centres in 29 countries. Patients were randomly assigned 1:1:1 while all three groups were open (nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy alone); this record covers the two arms compared in the primary report, 1581 patients concurrently randomised to nivolumab plus chemotherapy or chemotherapy alone. Chemotherapy was capecitabine plus oxaliplatin every 3 weeks or leucovorin, fluorouracil and oxaliplatin every 2 weeks. Primary endpoints for nivolumab plus chemotherapy versus chemotherapy: OS or PFS by blinded independent central review in patients with PD-L1 combined positive score (CPS) of 5 or more.
- Primary endpoint
- OS, PFS
- Arms
- Chemotherapy alone (control, n = 792): Capecitabine plus oxaliplatin or leucovorin, fluorouracil and oxaliplatin
- Nivolumab plus chemotherapy (experimental, n = 789): Nivolumab (360 mg every 3 weeks or 240 mg every 2 weeks) with the same chemotherapy
- People
- Janjigian YY, senior author Ajani JA
OSHR 0.71Δ median OS+3.3 monthsPFSHR 0.68OSHR 0.70 (95% CI 0.61–0.81)Δ 36-month OS+11 pointsΔ median OS+3.3 months
Show the numbers
| Endpoint | Analysis | Nivolumab plus chemotherapy | Chemotherapy alone | Effect |
|---|---|---|---|---|
| OSPD-L1 CPS 5 or more | primaryJanjigian 2021 | median 14.4 months (13.1–16.2) | median 11.1 months (10.0–12.1) | HR 0.71P<0.0001The hazard ratio is given with a 98.4% confidence interval of 0.59 to 0.86 (not a 95% interval); minimum follow-up 12.1 months to the 27 May 2020 data cutoff. Median OS 14.4 (95% CI 13.1-16.2) versus 11.1 (10.0-12.1) months, a 3.3-month improvement, from the full text. |
| PFSPD-L1 CPS 5 or morePFS by blinded independent central review | primaryJanjigian 2021 | — | — | HR 0.68P<0.0001The abstract gives the hazard ratio with a 98% confidence interval of 0.56 to 0.81 (not a 95% interval); minimum follow-up 12.1 months. |
| OSPD-L1 CPS 5 or more | long term-updateJanjigian 2024 | 21% at 3 y | 10% at 3 y | HR 0.70 (95% CI 0.61–0.81)Minimum follow-up 36.2 months. |
| OSPD-L1 CPS 5 or more (473 nivolumab plus chemotherapy, 482 chemotherapy) | long term-updateJanjigian 2024 | median 14.4 months (13.1–16.2) | median 11.1 months (10.0–12.1) | Median follow-up 47.4 months (range 36.2-61.5) with nivolumab plus chemotherapy and 47.3 months (36.6-61.3) with chemotherapy; clinical cutoff 31 May 2022. |
| OSAll randomly assigned patients (789 nivolumab plus chemotherapy, 792 chemotherapy) | long term-updateJanjigian 2024 | — | — | HR 0.79 (95% CI 0.71–0.88)Overall population from the 3-year report; clinical cutoff 31 May 2022. |
| PFSPD-L1 CPS 5 or morePFS by blinded independent central review | long term-updateJanjigian 2024 | 13% at 3 y | 8% at 3 y | HR 0.70 (95% CI 0.60–0.81) |
| ORRPD-L1 CPS 5 or moreObjective response rate per blinded independent central review | long term-updateJanjigian 2024 | 60% (55–65%) | 45% (40–50%) | — |
| Endpoint | Analysis | Nivolumab plus chemotherapy | Chemotherapy alone | Effect |
|---|---|---|---|---|
| OSPD-L1 CPS 5 or more | primaryJanjigian 2021 | median 14.4 months (13.1–16.2) | median 11.1 months (10.0–12.1) | HR 0.71P<0.0001The hazard ratio is given with a 98.4% confidence interval of 0.59 to 0.86 (not a 95% interval); minimum follow-up 12.1 months to the 27 May 2020 data cutoff. Median OS 14.4 (95% CI 13.1-16.2) versus 11.1 (10.0-12.1) months, a 3.3-month improvement, from the full text. |
| PFSPD-L1 CPS 5 or morePFS by blinded independent central review | primaryJanjigian 2021 | — | — | HR 0.68P<0.0001The abstract gives the hazard ratio with a 98% confidence interval of 0.56 to 0.81 (not a 95% interval); minimum follow-up 12.1 months. |
| OSPD-L1 CPS 5 or more | long term-updateJanjigian 2024 | 21% at 3 y | 10% at 3 y | HR 0.70 (95% CI 0.61–0.81)Minimum follow-up 36.2 months. |
| OSPD-L1 CPS 5 or more (473 nivolumab plus chemotherapy, 482 chemotherapy) | long term-updateJanjigian 2024 | median 14.4 months (13.1–16.2) | median 11.1 months (10.0–12.1) | Median follow-up 47.4 months (range 36.2-61.5) with nivolumab plus chemotherapy and 47.3 months (36.6-61.3) with chemotherapy; clinical cutoff 31 May 2022. |
| OSAll randomly assigned patients (789 nivolumab plus chemotherapy, 792 chemotherapy) | long term-updateJanjigian 2024 | — | — | HR 0.79 (95% CI 0.71–0.88)Overall population from the 3-year report; clinical cutoff 31 May 2022. |
| PFSPD-L1 CPS 5 or morePFS by blinded independent central review | long term-updateJanjigian 2024 | 13% at 3 y | 8% at 3 y | HR 0.70 (95% CI 0.60–0.81) |
| ORRPD-L1 CPS 5 or moreObjective response rate per blinded independent central review | long term-updateJanjigian 2024 | 60% (55–65%) | 45% (40–50%) | — |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.7 | 0.61–0.81 |
| OS | 0.79 | 0.71–0.88 |
| PFS | 0.7 | 0.6–0.81 |
- Nivolumab plus chemotherapy (experimental)
- Chemotherapy alone (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 chemotherapy | Chemotherapy alone |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 9 | 64.8% | 57.0% |
| 18 | 42.0% | 32.5% |
| 27 | 27.3% | 18.5% |
| 36 | 17.7% | 10.6% |
- Nivolumab plus chemotherapy (experimental)
- Chemotherapy alone (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 chemotherapy | Chemotherapy alone |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 9 | 64.8% | 57.0% |
| 18 | 42.0% | 32.5% |
| 27 | 27.3% | 18.5% |
| 36 | 17.7% | 10.6% |
Appears in
Sources
Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27-40.
Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, et al. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial. J Clin Oncol. 2024;42(17):2012-2020.