Abstract T100

Long term Follow-up of a Phase I Study Combinations of Ipilimumab, Nivolumab and Brentuximab Vedotin in Patients with Relapsed/Refractory Hodgkin Lymphoma: A trial of the ECOG-ACRIN Research Group (E4412: Arms A-I)

Background: E4412 is a Phase 1/2 ECOG-ACRIN sponsored study of the combinations of brentuximab (BV), nivolumab (N), and ipilimumab (I) in patients with R/R HL. Here we present the long-term safety and response data on the full cohort of patients treated in Phase 1 (Arms A-I).

Methods: Patients with confirmed R/R HL were treated in sequential dose escalation cohorts using 3+3 design. Additional patients were enrolled in expansion cohorts. Dose limiting toxicity (DLT) was evaluated within the first cycle of therapy.

Results: Between March 7, 2014, and Dec 28, 2017, 64 patients were enrolled; 3 patients were excluded due to ineligibility after enrolment. Thirty-five patients (57%) were refractory to their prior therapy; twenty-one (34%) had autologous stem cell transplant (SCT), 4 (6%) had prior alloSCT. Eight patients (13%) had prior BV. Safety: All 64 enrolled patients are included in the safety analysis. The most common (>30%) treatment-related grade 1–2 AEs were: nausea, peripheral sensory neuropathy, diarrhea, fatigue, elevated liver transaminases, anemia, and rash. Grade 3+ rash was more common in BV-I, in 22% of 23 patients compared with 7% of 41 patients in the other groups. Grade 3-4 events occurred in ten (43%) patients on BV-I, three (16%) patients on BV-N, and 12 (55%) patients in the triplet group. Two (3%) patients had treatment related death, one on BV-N (pneumonitis) and one in the BV-N-I group (dyspnea).

Response: The overall response rate (ORR) was 76% for BV-I, with a complete remission (CR) rate of 57%, for BV-N the ORR was 89% with a CR rate of 61% and for BV-N-I the ORR was 82% with a CR rate of 73%. The median follow-up (Q1, Q3) for PFS and OS is 2.24 (1.67, 2.72) years and 2.98 (2.83, 3.04) years. Duration of response (DOR) is 1.32 years for BV-I responders, not reached for BV-N and BV-N-I responders (Figure 1A). The median PFS is 1.1 years, NR, and 2.49 years for BV-I, BV-N and BV-N-I respectively (Figure 1B). The median OS has not been reached for any of the arms (Figure 1C).

Conclusion: Long term data from the Phase 1 component of E4412 shows no late safety concerns, and significant durability of response in both N containing arms with median follow-up of nearly 3 years. Analysis of the impact of transplant and depth of response will be updated by the time of the meeting. Optimization of this strategy is ongoing in E4412, now a randomized phase 2 study comparing the doublet of BV-N to the triplet of BV-N-I.