Table 3.
Clinical trials of anti-programmed death-1 and anti-programmed death ligand-1 in melanoma.
| Phase/trial (author, year) | Drug/dose | Patients | Grade 3–4 toxicities (n, %) | Overall response rate (%) | PFS (%) | OS (months) | Ref. |
|---|---|---|---|---|---|---|---|
| Phase I | |||||||
| Nivolumab plus ipilimumab in advanced melanoma (Wolchok et al., 2013) | Nivolumab/1 mg/kg; ipilimumab 3 mg/kg; given either concurrently or sequentially | 86 patients with advanced melanoma (stage III or IV) | Concurrent group: Any grade 3–4 toxicity (22, 42) Lipase elevation (3, 6) Hepatic disorder (8, 15) Pneumonitis, nonfatal (1, 2) Gastrointestinal disorder (5, 9) Renal disorder (3, 6) Rash (2, 4) Hypophysitis (1, 2) Sequential group: Any grade 3–4 toxicity (6, 18) Elevated lipase (2, 6) Amylase elevation (1, 3) Adrenal insufficiency (1, 3) Hypophysitis (1, 3) |
Concurrent group: Overall response rate (40) (16 patients with ≥80% tumor reduction) Sequential group: Overall response rate (20) Four patients with ≥80% tumor reduction |
Not reported | Not reported | [37] |
| Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma (Hamid et al., 2013) | MK-3475/10 mg/kg every 2–3 weeks, 2 mg/kg every 3 weeks | 135 patients with advanced melanoma (ocular excluded) who had either been treated with ipilimumab (n = 48) or two other prior lines of therapy (n = 87) | Any grade 3–4 toxicity (17, 13) Hypothyroidism (1) Diarrhea (1) Abdominal pain (1) Fatigue (2) Decreased appetite (1) AST elevation (2) Renal failure (2) Rash (3) Pruritus (1) |
Overall response rate (38) 10 mg/kg every 2 weeks (52) 10 mg/kg every 3 weeks (27) 2 mg/kg every 3 weeks (25) |
>7 months | Median OS not yet reached | [45] |
| Survival and long-term follow-up of safety and response in patients with advanced melanoma in a Phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538) (Sznol et al., 2013)† | Nivolumab/0.1–10 mg/kg (expansion cohort) | 107 patients with advanced melanoma | Any grade 3–4 toxicity (21%) Lymphopenia (3%) Lipase elevation (2%) Diarrhea (2%) Endocrine disorder (2%) Hepatitis (1%) |
31 | Not reported | Median OS (16.8) At 1 year: 50 patients at risk At 2 years: 24 patients at risk At 3 years: one patient at risk |
[30] |
| Phase II | |||||||
| Clinical activity, safety and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (Hamid et al., 2013)† | MPDL3280A/1–20 mg/kg every 3 weeks | 45 patients with advanced melanoma | Any grade 3–4 toxicity (33%) Hyperglycemia (7%) ALT elevation (7%) AST elevation (4%) |
Overall response rate (26) | At 24 weeks (35) | Not yet reported | [46] |
†
American Society of Clinical Oncology 2013 annual meeting abstract.
ALT: Alanine aminotransferase; AST: Aspartate Aminotransferase; OS: Overall survival; PD-1: Programmed death-1; PD-L1: Programmed death ligand-1; PFS: Progression-free survival.