Combination of immunotherapy and other targeted therapies in advanced cutaneous melanoma

Figures & data

Table 1. Overview of clinical trials featuring therapies or combinations in melanoma patients. NIVO: Nivolumab; pts: patients; ORR: Overall Response Rate; OS: Overall Survival; DOR: Duration of Response; HR: Hazard ratio; PEMBRO: Pembrolizumab; PFS: Progression Free Survival; TRAEs: treatment related adverse events; ITT: Intention-to-treat; IPI: Ipilimumab

Study	Patients	Design	Outcomes
NCT01968109	68 pretreated pts with unresectable or metastatic CM	Phase 1/2 trial of Relatimab (anti-LAG-3) plus NIVO	ORR = 11.5%, DCR = 49%. No major toxicities
CA224-047 (NCT03470922)	700 naïve pts with unresectable or metastatic CM	Phase 2/3 trial of of Relatimab (anti-LAG-3) plus NIVO vs NIVO	Ongoing
OPTiM (NCT00769704)	436 naïve pts with unresectable or metastatic CM	Phase 3 trial of intralesional T-VEC (oncolytic virus) vs subcutaneous GM-CSF	T-VEC improved ORR (31.5% vs 16.9%) and mOS (23.3 vs 18.9 mo, HR 0.79; 95% CI 0.62–1.00; p = .0494)
Illuminate-204 (NCT02644967)	49 pretreated pts with unresectable or metastatic CM	Phase 1/2 trial of Tilosotolimod (TLR-9 agonist) plus IPI in pts with advanced CM	ORR = 22.4%, DCR = 71%, mDOR = 11 mo, mPFS = 5.1 mo, mOS = 21 mo.
Illuminate-301 (NCT03445533)	Patients with unresectable or metastatic CM	Phase 3 trial of Tilosotolimod (TLR-9 agonist) plus IPI vs IPI	Ongoing
PIVOT-02 (NCT02983045)	38 naïve pts with metastatic CM	Phase 1/2 trial of Bempegaldesleukin (PEG-IL2) plus NIVO	ORR = 59.5% (18.9% complete responses)
PIVOT-IO-010 (NCT03635983)	760 naïve pts with metastatic CM	Phase 3 trial of Bempegaldesleukin (PEG-IL2) plus NIVO vs NIVO	Ongoing
PROPEL (NCT03138889)	Naïve pts with unresectable or metastatic CM	Phase 1/2 trial of Bempegaldesleukin (PEG-IL2) plus PEMBRO	Ongoing
IMspire170 (NCT03273153)	446 naïve pts with BRAFV600 mutated wild type unresectable or metastatic CM	Phase 3 trial Atezolizumab plus Cobimetinib versus PEMBRO	The combination not improved nor mPFS (5.5 vs 5.7 mo, HR 1.15; 95% CI 0.88–1.50; p = .295) or OS (NR in both arms, HR 1.06; 95% CI 0.69–1.61)
IMspire150 (NCT02908672)	514 naïve pts with BRAFV600 mutated unresectable or metastatic CM	Phase 3 trial Atezolizumab plus Vemurafenib and Cobimetinib vs Vemurafenib and Cobimetinib	The triplet improved mPFS (15.1 vs 10.6 mo, HR 0.78; 95% CI 0.63–0.97; p = .025) and mOS (21 vs 12 mo)
COMBI-i (NCT02908672)	532 naïve pts with BRAFV600 mutated unresectable or metastatic CM	Phase 3 trial of Spartalizumab, Dabrafenib, and Trametinib vs Dabrafenib and Trametinib	The triplet slightly improved mPFS in the ITT population (16.2 vs 12 mo, HR 0.82; 95% CI, 0.655–1.027; p = .042), but significantly improved mPFS in the TMBhigh subpopulation (23.9 vs 11.8 mo)
KEYNOTE-022 (NCT02130466)	120 naïve pts with BRAFV600 mutant unresectable or metastatic CM	Phase 2 trial of PEMBRO, Dabrafenib, and Trametinib vs Dabrafenib and Trametinib	The triplet increases mPFS (16.9 vs 10.7 mo, HR 0.53; 95% CI 0.34 to 0.83) and mOS (NR vs 26.3 mo, HR 0.64; 95% CI 0.38 to 1.06), but increased grade 3–5 TRAEs (58% vs 25%)
LEAP-004 (NCT03776136)	104 pretreated pts with unresectable or metastatic CM	Phase 2 trial of PEMBRO and Lenvatinib	ORR = 21.4%, DCR = 65%, mPFS = 4.2 mo