Table 2.
Phase II and III clinical trials of programmed cell death 1 inhibitors in advanced gastroesophageal cancer
| n (phase) | Experimental arm | Control or reference arm | Primary endpoint | Results | Ref. |
| 160 (I/II) | N1 + I3: Nivolumab 1 mg/kg every 2 wk and ipilimumab 3 mg/kg every 3 wk | N3: Nivolumab 3 mg/kg every 2 wk | ORR | N3: ORR 12%, PD-L1 ≥ 1% ORR 19%, PD-L1< 1% ORR 12% | CheckMate 032 [54] |
| N3 + I1: Nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 wk | N1+I3: ORR 24%, PD-L1≥ 1% ORR 40%, PD-L1< 1% ORR 22% | ||||
| Gastric, esophageal, or GEJ cancer | N3+I1: ORR 8%, PD-L1 ≥ 1% ORR 23%, PD-L1 < 1% ORR 0% | ||||
| 259 (II) | Cohort 1 (after ≥ 2 lines of therapy): Pembrolizumab 200 mg every 3 wk up to 2 yr, PD, decision to withdraw, or unacceptable toxicity in gastric cancer | N/A | ORR, safety, tolerability | Overall ORR 11.2% (95%CI: 7.6-15.7), CR 1.9% (95%CI: 0.6-4.4), PR 9.3% (95%CI: 6.0-13.5), SD 17% (95%CI: 12.6-22.1), PD 55.6% (95% CI 49.3-61.7) | KEYNOTE 059 [56] |
| PD-L1+ ORR 15.5% (95% CI 10.1-22.4), PD-L1- ORR 5.5% (95% CI 2.0-11.6) | |||||
| 25 (II) | Cohort 2 (1st line): pembrolizumab 200 mg every 3 wk for up to 2 yr, cisplatin (80 mg/m2 day 1), and 5-FU (800 mg/m2 D1-5 Q3W) or capecitabine (1000 mg/ m2 bid) | N/A | Safety, ORR | Cohort 2: ORR 60% (39-79) overall, 73% (45-92) PD-L1+, 38% (9-76) PD-L1-. Median PFS 7 mo | KEYNOTE 059 [55] |
| 31 (II) | Cohort 3 (PD-L1+, 1st line): pembrolizumab 200 mg every 3 wk for up to 2 yr | N/A | Safety, ORR | Cohort 3: ORR 26% (12-45). Median PFS 3 mo | KEYNOTE 059 [55] |
| Gastric or GEJ cancer | |||||
| 41 (II) | Pembrolizumab 10 mg/kg every 2 wk | Cohort B: MMR-proficient CRC | ORR, PFS | MMR-deficient CRC: ORR 40%, PFS 78%; median PFS and OS not reached | Keynote-016 [58] |
| Cohort A: Mismatch repair (MMR)-deficient colorectal cancers (CRC) | MMR-proficient CRC: ORR 0%, PFS 11%; median PFS 2.2 mo, OS 5.0 mo | ||||
| Cohort C: MMR-deficient non-CRC | MMR-deficient non-CRC: ORR 71%, PFS 67% | ||||
| 86 (II) | Pembrolizumab 10 mg/kg every 2 wk for MMR-deficient cancers (12 tumor types) | N/A | ORR, PFS | Objective radiographic response 53%, CR 21%; median PFS and OS not reached | [59] |
| 493 (III) | Nivolumab 3 mg/kg every 2 wk until unacceptable toxicity or PD in gastric/GEJ cancers | Placebo | OS | Nivolumab: median OS 5.32 mo, 6-mo OS 46.4%, 12-mo OS 26.6%, ORR 11.2%, median PFS 1.61 mo | ATTRACTION-02 [57] |
| Placebo: median OS 4.14 mo, 6-mo OS 34.7%, 12-mo OS 10.9%, ORR 0%, median PFS 1.45 mo |
PD: Progressive disease; ORR: Overall response rate; CI: Confidence interval; OS: Overall survival.