Checkmate 205: Nivolumab (nivo) in classical Hodgkin lymphoma (cHL) after autologous stem cell transplant (ASCT) and brentuximab vedotin (BV)—A phase 2 study.

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Background: cHL is characterized by amplification at 9p24.1, causing overexpression of PD-1 ligands. Thus, cHL may be uniquely sensitive to PD-1 blockade. Nivo is a fully human IgG4 immune checkpoint inhibitor targeting PD-1 that showed promising results in a phase 1b study (NCT01592370) in pts with relapsed/refractory cHL (Ansell SM et al NEJM 2015;372:311–9), who currently have limited treatment options. Methods: This study evaluated the efficacy and safety of nivo in pts with cHL who had received BV after failed ASCT, as Cohort B of the larger Phase 2 Checkmate 205 study (NCT02181738). Nivo was given at 3 mg/kg IV q2w. Response was assessed by independent radiologic review committee (IRRC) and investigators (Inv), using 2007 IWG criteria. Primary endpoint was IRRC ORR. Results: The main characteristics of 80 treated cHL pts were: median age 37 y, median (range) 4 prior regimens (3–15). 90% of pts had drug-related AEs: 25% G3–4, 1% G5 (multi-organ failure). Most common drug-related AEs were fatigue (25%), infusion reaction (IR; 20%) and rash (16%). Most common SAEs were pyrexia, tumor progression, arrhythmia, IR, septic meningitis, and pneumonia ( ≤ 4% each). Select immune-related AEs, all G1–2, occurred in 26%. At database lock (DBL; October 2015), median (range) follow-up was 8.9 mo (1.9–11.7). 64% of pts remained on therapy; main reason for discontinuation was disease progression (16%). IRRC ORR (95% CI) was 66% (54.8–76.4); CR and PR rates were 8.8% (3.6–17.2) and 57.5% (45.9–68.5), respectively. Inv ORR, a pre-specified secondary endpoint, was 73% (61.4–81.9); CR and PR rates were 27.5% (18.1–38.6) and 45.0% (33.8–56.5). 62% (33/53) of IRRC responders remained in response at DBL. 6 pts elected to stop nivo and undergo stem cell transplant, all of these pts were alive at data cut-off. IRRC 6-mo PFS was 77%; OS was 99%. In 43 pts who had no prior BV response, nivo treatment resulted in an IRRC ORR of 72% (31/43). Conclusions: Nivo demonstrated a high response rate, long-lasting responses, and an acceptable safety profile in pts with cHL after ASCT and BV, including pts with no prior BV response. PFS and OS are encouraging in this heavily pretreated population. Clinical trial information: NCT02181738.