Novel efficacy criteria for antitumor activity to immunotherapy using the example of ipilimumab, an anti-CTLA-4 monoclonal antibody

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3008 Background: Ipilimumab represents a new class of immunotherapeutic agent. Antitumor activity (CR, PR, or SD) to ipilimumab in melanoma can take weeks to months and 3 main clinical patterns were observed: (1) immediate, (2) late (after progression; PD), and (3) in the presence of new lesions. Modified World Health Organization (mWHO) response criteria do not recognize the latter 2 patterns. PD by mWHO prompts cessation of treatment and follow-up. To capture the patterns of activity, novel or broader assessment criteria are needed. Methods: Patients (pts) with advanced melanoma in 3 phase II trials received 10 mg/kg ipilimumab induction dosing every 3 weeks (Q3W) × 4. Eligible pts continued maintenance therapy Q12W. Activity was assessed using conventional mWHO and novel immune-related response criteria (irRC) developed using the thresholds for response previously defined by conventional mWHO criteria. Contrary to mWHO, irRC (1) only considered measurable lesions (>1cm), (2) defined total tumor burden (TB) as the sum of index lesions identified at baseline and new lesions detected after baseline, (3) aimed for follow-up post PD to detect late activity. Pts with stable disease (SD) and slow decline in tumor volume >25% from baseline were included as clinically meaningful as they had objective activity without reaching the 50% threshold of PR. The totality of pts with an objective reduction of TB from baseline (CR, PR, SD with >25% decline) is reported. Results: 284 pts were evaluated. Conventional antitumor response rates (mWHO) in pts treated with 10 mg/kg ipilimumab monotherapy were 5.8%, 11.1%, and 15.8%, respectively. The totality of pts with an objective reduction of TB from baseline per irRC were 25.8%, 15.3%, and 30.9%, respectively. Conclusions: irRC may more accurately describe response to immunotherapy. Following pts for late response may avoid premature treatment cessation in pts with PD prior to response. Possible mechanisms underlying the clinical activity patterns are late effects of the immune system, sufficient availability of antigen for immune recognition, and increase of tumor volume through lymphocytic infiltration/edema before response. irRC need prospective validation and confirmation by survival data. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Medarex Bristol-Myers Squibb, Medarex