CHICAGO — Heavily pretreated patients with metastatic melanoma who received the humanized anti-PD-1 monoclonal antibody pidilizumab demonstrated encouraging rates of 12-month OS, according to results of a phase 2 study presented at the ASCO Annual Meeting.
“Activity was previously seen [with pidilizumab] in two lymphoma populations in phase 2 studies,” researcher Michael B. Atkins, MD, deputy director of Georgetown-Lombardi Comprehensive Cancer Center in Washington, and professor of oncology and medicine at Georgetown University School of Medicine, said during a presentation. “Correlative studies in those lymphoma populations supported a PD-1/PD-L1–linked mechanism of action, and importantly there was no change or an increase in PD-1–positive CD4 and CD8 lymphocytes and CD14 monocytes following the drug, excluding antibody-dependent cellular cytotoxicity of PD-1–positive cells as a consequence of therapy.”
Atkins and colleagues assigned 103 patients 1:1 to 1.5 mg/kg or 6 mg/kg IV pidilizumab (CT-011, CureTech) every other week for up to 54 weeks. Patients were stratified according to prior therapy with ipilimumab (Yervoy, Bristol-Myers Squibb).
Most patients (75%) had stage M1c disease, 15.5% had brain metastases and 33% had disease that had metastasized to three or more organs. Seventy-seven percent of patients had received prior systemic therapy for melanoma, including ipilimumab (51%), a BRAF inhibitor (7.8%) or cytokine therapy (44%).
Forty-five percent of patients did not respond to previous therapy, and 45% received the study treatment within 4 months of previous therapy.
Among all patients, the objective response rate — calculated using immune-related response criteria — was 5.9% (90% CI, 2.3-12). Patients who received the 1.5-mg/kg dose and who received previous ipilimumab demonstrated a response rate of 10% (90% CI, 1.8-28.3).
Researchers reported a higher rate of immune-response stable disease (53.7% vs. 20.5%) and longer median PFS (2.8 months vs. 1.9 months) among patients who underwent prior ipilimumab treatment.
Among all patients, the 12-month OS rate was 64.5% (90% CI, 55.6-72.0). Researchers observed no significant differences in survival with regard to dose level, disease strata or other therapies.
Among 26 patients who did not receive previous or post-study ipilimumab, 55.7% (90% CI, 35.6-71.8) achieved 12-month OS. The 12-month OS rate among 63 patients with BRAF V600 wild-type tumors was 69.3% (90% CI, 58.2-78.1), and the rate among 77 patients with M1c disease was 67.2% (90% CI, 57.0-75.7).
Fatigue (43%), diarrhea (22.5%) and arthralgia (21%) were the most frequently observed adverse events, but they were not dose-related, Atkins said. The most common severe adverse events were pneumonia (5%) and dyspnea (3%).
“The study missed its primary endpoint of overall response but met its secondary endpoint for survival,” Atkins said. “The 12-month survival in heavily pretreated patients appears to be better than anticipated and similar to that reported for other anti-PD-1 antibodies, and the reason for that is something that could be subject to debate. Strategies to improve the response rate should be considered, including higher doses … or combinations with other therapeutics.”
For more information:
Atkins MB. Abstract #9001. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.
Disclosure: Researchers report employment/leadership positions with or providing expert testimony to CureTech.