A phase 2 multicenter, randomized, open-label, study has evaluated the safety and efficacy of Pidilizumab ( CT-011 ), a humanized anti-PD-1 IgG1k, in patients with metastatic melanoma.
Eligibility criteria were: measurable disease; stage IV clearly progressive; ECOG 0-1; less than or equal to 3 prior systemic therapies for metastatic melanoma; stabilized brain mets allowed; 6 weeks from prior Ipilimumab, no prior PD-1/PD-L1/PD-L2 blockade.
Patients were randomized to 2 dose levels ( 1.5 or 6 mg/kg IV q2 wk X 27 ), each with 50 patients and each balance stratified by prior Ipilimumab ( yes/no ).
In total, 103 patients were randomized; 75% M1c, 15.5% brain mets, 30% elevated LDH, 33% disease spread to 3 or more organs.
77% received prior systemic therapy for metastatic melanoma; 51% prior Ipilimumab, 7.8% prior Braf inhibitor, 44% prior biologics ( cytokines ).
45% did not respond to most recent therapy.
A total of 45% received Pidilizumab less than 4 months after prior therapy. Overall response rate ( ORR ) using irRC for all patients was 5.9% [ 90% CI: 2.3, 12.0 ] and 10.0% [ 90% CI: 1.8, 28.3 ] for 1.5mg/kg and prior Ipilimumab.
Patients with prior Ipilimumab had higher irSD ( 53.7% vs 20.5% ) and slightly longer median progression-free survival ( 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 patients without prior or post-study Ipilimumab ( n=26 ) was 55.7% [ 90% CI: 35.6, 71.8 ], 12mo survival for patients with BRAF V600 WT tumors ( n=63 ) was 69.3% [ 90% CI: 58.2, 78.1 ].
Survival at 12 months for M1c patents ( n=77 ) was 67.2%; [ 90% CI: 57.0, 75.5 ].
The most frequent adverse effects were fatigue ( 43% ), diarrhea ( 22.5% ), arthralgia ( 21% ) and severe adverse reactions of pneumonia ( 5% ) and dyspnea ( 3% ).
In conclusion, despite low response rates, Pidilizumab therapy results in substantial survival at 12 months in heavily pretreated patients.
The survival at 12 months appears comparable to that of other anti- PD-1 monoclonal antibodies.
Treatment is very well tolerated.
Further studies of Pidilizumab in patients with metastatic melanoma are warranted, preferably in combination with other therapeutics. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Meeting, 2014