Table 1.
Clinical trials of antibodies to PD-1
| Drug | NCT | Phase | Design | Population | N | Key findings /Conclusions |
|---|---|---|---|---|---|---|
| Melanoma | ||||||
| Nivolumab | NCT00730639 | 1 | Dose finding and dose expansion | Advanced melanoma | 107 | OS =43% at 2 years which compares favorably with historical population |
| NCT01176461 | 1 | Nivolumab +/− peptide vaccine (NY-ESO-1, gp100, MART-1) | Advance melanoma, Ipilimumab naïve and refractory | 90 | ORR=25.1%. No difference in response between Ipilimumab naïve and refractory or addition of vaccine to nivolumab. PD-L1 negative patients also responded. | |
| NCT01721772 | 3 | Nivolumab vs Dacarbazine | Metastatic melanoma without BRAF mutation | 418 | Significantly better 1 yr OS in nivolumab arm (72.9% vs 42.1%). Relatively well tolerated | |
| NCT01721746 | 3 | Nivolumab vs investigators choice | Metastatic melanoma after CTLA-4 or BRAF inhibitor therapy | 370 | Results in 167 patients showed higher ORR in nivolumab arm and durable tumor regression as well | |
| Pembrolizumab | NCT01295827 | 1 | Dose finding and dose expansion | Advanced melanoma including CTLA4 treated patients | 135 | ORR =38%. No difference in response between ipilimumab naïve and refractory. Acceptable safety profile and slightly better responses in the higher dose-10mg/kg arm |
| NCT01295827 | 1 | Nivolumab 2 mg/kg vs 10 mg/kg | Advanced melanoma whose disease progressed on ipilimumab | 173 | ORR=26% after ipilimumab therapy. No difference between the two drug doses. | |
| Pidilizumab | NCT01435369 | 2 | Pidilizumab 1.5 vs 6 mg/kg | Advanced melanoma | 103 | Low response rate of 5.9% |
| Non-small cell lung cancer | ||||||
| Nivolumab | NCT00730639 | 1 | Dose finding and dose escalation | Advanced malignancies | 296 | ORR=18.4% in NSCLC cohort. Low rate of Grade 3 SAE =14% |
| NCT01454102 | 1 | Nivolumab + Erlotinib | Stage IIB/IV NSCLC in EGFR mutated patients naïve or post progression | 21 | ORR=19% with an acceptable safety profile | |
| NCT01642004 | 3 | Open label randomized nivolumab vs docetaxel | Metastatic squamous cell lung cancer after 1 line of platinum based therapy | 272 | Superior OS in the nivolumab arm at 1 year (9.2 vs 6 mos.) with durable responses | |
| Pembrolizumab | NCT01295827 | 1 | Pembrolizumab at 2mg/kg or 10 mg/kg | Advanced NSCLC | 282 | ORR=21%, PD-L1+ tumors had higher response rates than negative tumors |
| Genitourinary malignancies | ||||||
| Nivolumab | NCT01354431 | 2 | Nivolumab at 0.3 vs 2 vs 10 mg/kg doses | Previously treated RCC with VEGF inhibitors | 168 | ORR =21% across all 3 arms with a tolerable safety profile. No dose response relationship was response |
| Pembrolizumab | NCT01848834 | 1b | Dose finding study | PD-L1+ >1% and advanced urothelial cancer | 33 | ORR=24%, with CR in 10% with an acceptable safety profile |
| Other cancers | ||||||
| Nivolumab | NCT01592370 | 1 | Dose escalation and dose expansion | Relapsed, refractory Hodgkin lymphoma | 23 | ORR=87% with a PFS at 24 weeks of 86% with an acceptable safety profile. |
| Nivolumab | NCT01876511 | 2 | Pembrolizumab 10 mg/kg q2 weeks | Advanced malignancies with or without mismatch deficiency | 41 | IrPFS = 78% vs 11% for mismatch deficient vs proficient colorectal cancers. |
ORR- Objective response rate; PFS - Progression free survival; irPFS – immune related Progression Free survival; OS - Overall Survival, CR - Complete response; NSCLC - Non-small cell lung cancer; SAE - Serious Adverse Events