$PVCT: Merck Anti-PD-1 Agent MK-3475 (lambrolizumab) and Breakthrough Therapy Designation

Last week, Merck announced the FDA had designated lambrolizumab (MK-3475) as a Breakthrough Therapy for the treatment of patients with advanced melanoma.

On MK-3475 & BTD: "Wendy Selig, president and chief executive of the Melanoma Research Alliance, an advocacy organization based in Washington, DC, welcomes the new designation for lambrolizumab. “We view it as a really important step in the process of creating this ‘all hands on deck’ mentality, where you have a serious unmet medical need and where there are big gaps in terms of what’s available,” she says."

In November 2012, Merck presented early-stage interim data for MK-3475 of a single-arm, open-label Phase IB study. "Patients were administered MK-3475 in one of three regimens: low dose every 3 weeks, high dose every 3 weeks and high dose every 2 weeks. Following an initial disease evaluation, patients received one of the three regimens of MK-3475. After 12 weeks, disease status was evaluated by the investigator and compared to baseline using immune-related response criteria (irRC). Those patients demonstrating stable disease or response at the 12-week evaluation time point continued to receive MK-3475 and follow-up monitoring."

"Data has so far been obtained for 85 of the 132 patients enrolled in the study. Of those patients, a total of 43 patients (51 percent) showed an objective anti-tumor response, and of those, 8 patients (9 percent) showed a complete response at or after the 12-week assessment. Notably, of the 27 patients who had previously been treated with ipilimumab monotherapy, the current standard of care for late-stage melanoma, 11 patients (41 percent) showed an objective anti-tumor response to MK-3475 monotherapy; none of those patients showed a complete response."

PV-10's final MM Phase 2 data from ESMO 2012:

• An Objective Response Rate (OR) of 51% in subjects' target lesions (25% Complete Response and 26% Partial Response),
• 69% disease control in these lesions (combined Complete, Partial and Stable Response subjects);
• 33% of subjects having an untreated bystander melanoma lesion achieved an OR in their bystander lesions while 50% achieved disease control in these lesions,
• Response of bystander lesions was highly correlated with outcome in treated target lesions, with a bystander lesion OR of 61% in subjects achieving complete or partial response in their target lesions versus 18% bystander lesion OR in subjects that did not achieve this level or response in their target lesions, and 
• Stage III subjects experienced a substantially higher target lesion response rate (60% OR and 79% disease control) versus Stage IV subjects (22% and 33%, respectively).