Monotherapy and combination studies of nivolumab in NSCLC and melanoma included in DOR analyses
| Study #/population | Study objective | Study design and treatment regimen | ORR per RECIST | Median OS, months HR (CI) |
| NSCLC | ||||
| CheckMate 012/chemo-naive recurrent stage IIIb or stage IV NSCLC34 | To assess safety and tolerability | Phase I, randomized (1:1:1), open-label, multiple-cohort study of NIVO as monotherapy or in combination with IPI NIVO (3 mg/kg Q2W) +IPI (1 mg/kg Q12W) cohort 1 (n=38) NIVO (3 mg/kg Q2W) +IPI (1 mg/kg Q6W) cohort 2 (n=39) | 47% (cohort 1) 38% (cohort 2) | Not available |
| CheckMate 017/previously treated advanced or metastatic SQ NSCLC after one prior platinum doublet-based chemo regimen39 | To compare OS of NIVO with docetaxel | Phase III, randomized (1:1), open-label study of NIVO (n=135) vs docetaxel (n=137) NIVO: 3 mg/kg IV Q2W Docetaxel: 75 mg/m2 Q3W | 20% vs 9% | 9.2 v 6.0 HR=0.59 (95% CI 0.44 to 0.79) |
| CheckMate 026/chemo-naive stage IV or recurrent PD-L1-expressing NSCLC32 | To compare PFS (BICR) of NIVO with IC chemo in patients with ≥5% PD-L1+ tumor expression | Phase III, open-label, randomized study of NIVO (n=271) vs IC chemo (n=270) NIVO: 3 mg/kg IV Q2W IC chemo: gemcitabine with cisplatin or carboplatin; paclitaxel with carboplatin; pemetrexed with cisplatin or carboplatin Q3W | 26% vs 33% | 14.4 vs 13.2 HR=1.02 (95% CI 0.80 to 1.30) |
| CheckMate 057/previously treated advanced or metastatic NSQ NSCLC after one prior platinum doublet-based chemo regimen4 | To compare OS of NIVO with docetaxel | Phase III, randomized (1:1), open-label study of NIVO (n=292) vs docetaxel (n=290) NIVO: 3 mg/kg IV Q2W Docetaxel: 75 mg/m2 Q3W | 19% vs 12% | 12.2 vs 9.4 HR=0.73 (96% CI 0.59 to 0.89) |
| CheckMate 063/advanced, refractory SQ NSCLC after platinum doublet-based chemo and at least one additional systemic therapy33 | To assess ORR (BICR) of NIVO | Single-arm, phase II study of NIVO monotherapy (n=117) NIVO: 3 mg/kg IV Q2W | 15% | 8.2 |
| Melanoma | ||||
| CheckMate 037/advanced melanoma s/p anti-CTLA-4 therapy, and if BRAF V600 mutation +s/p BRAF inhibitor37 | To estimate ORR in the NIVO group and compare OS of NIVO with IC | Phase III, randomized (2:1), open-label study of NIVO (n=272) vs IC chemo (n=133) NIVO: 3 mg/kg IV Q2W IC: dacarbazine 1000 mg/m2 IV Q3W or carboplatin (AUC 6) IV and paclitaxel 175 mg/m2 Q3W | 26.5% vs 9.0% | 15.74 vs 14.39 HR=0.95 (95.54% CI 0.73 to 1.24) |
| CheckMate 066/previously untreated, BRAF WT unresectable or metastatic melanoma36 | To compare the OS of NIVO with dacarbazine | Phase III, randomized (1:1), double-blind study of NIVO (n=210) vs dacarbazine (n=208) NIVO: 3 mg/kg IV Q2W Dacarbazine: 1000 mg/m2 Q3W | 40.0% vs 13.9% | NR vs 10.8 HR=0.42 (99.79% CI 0.25 to 0.73) |
| CheckMate 067/previously untreated, unresectable, or metastatic melanoma35 | To compare PFS and OS of NIVO monotherapy with IPI monotherapy, NIVO+IPI to IPI monotherapy | Phase III, randomized (1:1:1), double-blind study of NIVO (n=316) or NIVO+IPI (n=314) vs IPI (n=315) NIVO: 3 mg/kg IV Q2W NIVO+IPI: NIVO 1 mg/kg+IPI 3 mg/kg Q3W for four doses then NIVO 3 mg/kg Q2W IPI: 3 mg/kg Q3W for four doses | PD-L1 positive vs negative 57.5% vs 41.3% (NIVO) 72.1% vs 54.8% (NIVO+IPI) 21.3% vs 17.8% (IPI) | NR vs 19.98 (NIVO mono vs IPI mono) – HR=0.63 (98% CI 0.48 to 0.81) |
| CheckMate 069/previously untreated, unresectable, or metastatic melanoma32 | To compare ORR, as determined by investigators, of NIVO+IPI with IPI monotherapy | Phase II, randomized (2:1), double-blind study of NIVO+IPI (n=95) vs IPI (n=47) NIVO+IPI: NIVO 1 mg/kg+IPI 3 mg/kg Q3W for four doses; then NIVO 3 mg/kg Q2W IPI: 3 mg/kg Q3W for four doses | 61.1% vs 10.8% among BRAF WT patients | NR vs NR HR=0.73 (95% CI 0.39 to 1.36) |
| SCCHN | ||||
| CheckMate 141/recurrent or metastatic platinum-refractory SCCHN41 | To compare OS of NIVO monotherapy with IC | Phase III, randomized (2:1), open-label study of NIVO (n=240) vs IC (n=121) NIVO: 3 mg/kg IV Q2W IC: cetuximab, methotrexate, or docetaxel | 13.3% vs 5.8% | 7.5 vs 5.1 HR=0.70 (97.73% CI 0.51 to 0.96) |
| RCC | ||||
| CheckMate 025/advanced or metastatic clear-cell RCC previously treated with 1–2 regimens of antiangiogenic therapy40 | To compare OS of NIVO monotherapy with everolimus | Phase III, randomized (1:1), open-label study of NIVO (n=410) vs everolimus (n=411) NIVO: 3 mg/kg IV Q2W Everolimus: 10 mg PO daily | 25% vs 5% | 25.0 vs 19.6 HR=0.73 (98.5% CI 0.57 to 0.93) |
| CheckMate 214/previously untreated, advanced, or metastatic RCC42 | To compare OS, PFS, and ORR of NIVO+IPI with sunitinib | Phase III, randomized (1:1) study of NIVO+IPI (n=550) vs sunitinib (n=546) NIVO+IPI: NIVO 3 mg/kg+IPI 1 mg/kg IV Q3W for four doses; then NIVO 3 mg/kg Q2W Sunitinib: 50 mg PO daily for 4 weeks, then 2 weeks off | 39% vs 32% | NR vs 32.9 HR=0.68 (99.8% CI 0.49 to 0.95) |
AUC, area under the curve; BICR, blinded independent central review; chemo, chemotherapy; CTLA-4, cytotoxic T lymphocyte antigen-4; DOR, duration of response; IC, investigator’s choice; IPI, ipilimumab; IV, intravenous; MONO, monotherapy; NIVO, nivolumab; NR, not reached; NSCLC, non-small-cell lung cancer; NSQ, non-squamous; ORR, objective response rate; OS, overall survival; PD-L1, programmed death ligand 1; PFS, progression-free survival; PO, take by mouth; QXW, every X weeks; RCC, renal cell carcinoma; RECIST, Response Evaluation Criteria in Solid Tumors; SCCHN, squamous cell carcinoma of the head and neck; s/p, status post; SQ, squamous; WT, wild type.