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Phase 2, multicenter, safety and efficacy study of pidilizumab in patients with metastatic melanoma.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Pidilizumab (CT-011), a humanized anti PD-1 IgG1k, was studied in two Phase 2 studies in aggressive and indolent lymphomas showing clinical activity correlated with PD-1/PD-L1+ lymphocytes. Thus, we initiated a Phase 2 multicenter, randomized, open-label, study to evaluate the safety and efficacy of pidilizumab in patients (pts) with metastatic melanoma (MM). Methods: Eligibility criteria: measurable disease; Stage IV clearly progressive; ECOG 0-1; ≤ 3 prior systemic therapies for MM; stabilized brain mets allowed; 6 weeks from prior ipilimumab (Ipi), no prior PD-1/PD-L1/PD-L2 blockade. Pts were randomized to 2 dose levels (1.5 or 6 mg/kg IV q2 wk X 27), each with 50 pts and each balance stratified by prior Ipi (yes/no). Results: 103 pts were randomized; 75% M1c, 15.5% brain mets, 30% elevated LDH, 33% disease spread to ≥ 3 organs. 77% received prior systemic therapy for MM; 51% prior Ipi, 7.8% prior Braf inhibitor, 44% prior biologics (cytokines). 45% did not respond to most recent therapy. 45% received pidilizumab less than 4 months after prior therapy. ORR using irRC for all pts was 5.9% [90% CI: 2.3, 12.0] and 10.0% [90% CI: 1.8, 28.3] for 1.5mg/kg & prior Ipi. Pts with prior Ipi had higher irSD (53.7% vs 20.5%) and slightly longer median PFS (2.8 vs 1.9 months). Overall Survival at 12 months (12mo survival) was 64.5% (90% CI: 55.6, 72.0), with insignificant differences between strata or doses and irrespective of therapies given before study entry or after study withdrawal; 12mo survival for pts without prior or post-study Ipi (n=26) was 55.7% [90% CI: 35.6, 71.8], 12mo survival for pts with B-RAF V600 WT tumors (n=63) was 69.3% [90% CI: 58.2, 78.1]. 12mo survival for M1c pts (n=77) was 67.2%; [90% CI: 57.0, 75.5]. The most frequent AEs were fatigue (43%), diarrhea (22.5%), arthralgia (21%) and SAEs of pneumonia (5%) and dyspnea (3%). Conclusions: Despite low response rates, pidilizumab therapy results in substantial 12mo survival in heavily pretreated pts. The 12mo survival appears comparable to that of other anti- PD-1 MAbs. Treatment is very well tolerated. Further studies of pidilizumab in pts with MM are warranted, preferably in combination with other therapeutics. Clinical trial information: NCT01435369.