BACKGROUND: Single agent strategies have not demonstrated deep and durable responses for the majority of patients with relapsed and refractory cHL (RR-cHL) and therefore effective and well tolerated combination therapies are needed. Both pembrolizumab and bendamustine have demonstrated single agent efficacy in RR-cHL with no overlapping toxicity.
AIMS: The ongoing investigator-initiated phase 2 KEsTREL-01 study aims to evaluate response, survival rates and safety of the combination of pembrolizumab and bendamustine (PB). The primary endpoint is ORR (CR and PR) and PET-CR rate for PB. Secondary endpoints include safety, tolerability and 2-year PFS and OS.
METHODS: Eligible patients (pts) are >18 years with RR-cHL after standard first-line therapy containing an anthracycline, have subsequently progressed after or are not candidates for ASCT, adequate organ function and ECOG PS 0-1. Prior pembrolizumab exposure is permitted, but not prior bendamustine therapy. Treatment regimen includes pembrolizumab 200 mg IV (day 1) and bendamustine 90 mg/m2 IV (days 1 & 2) every 21 days for up to 6 cycles. Patients achieving at least SD continue pembrolizumab monotherapy for 35 doses in total. Response is investigator-assessed by using Lugano 2014.
RESULTS: As of 31 May 2024, 21 pts have been enrolled: median age 36 (range 18-77), ECOG PS; 0 in 16 and 1 in 5 patients, median number of prior therapies 2 (range 1-6); 2 pts prior BV, 3 pts prior pembrolizumab; 6 pts had received prior radiation. Median number of treatment cycles received was 2 (range 2-34). 15 pts have discontinued treatment; 9 to receive alternative treatment, 3 for AEs, 2 for PD and one death on study (pulmonary infection). 10 pts proceeded to ASCT (1 patient taken off study due to AE proceeded to ASCT once AE resolved). For the first 20 pts, Grade 3+ treatment-related AEs included 1 each of: hypomagnesemia, hypocalcemia, anemia, dyspnea, lung infection, pneumonitis, neutropenia, acute kidney injury, hypotension, LV systolic dysfunction, sinus bradycardia and pain. The ORR in 20 evaluable patients was 100%, with CR 70% (14) and PR 30% (6). With a median follow-up of 7 months (range 0.7-26), estimated median PFS is 16.7 months (4 events) and median OS has not been reached (3 events).
CONCLUSION: Preliminary results of the phase 2 KEsTREL-01 study demonstrate an encouraging CR rate and acceptable toxicity for combination PB in RR-cHL, which can successfully bridge patients to ASCT. Accrual is ongoing.
Chathuri Abeyakoon, Semira Sheikh, Lisa Wang, Tomohiro Aoki, Sita Bhella, Robert Kridel, Vishal Kukreti, Anca Prica, Abi Vijenthira, Rob Laister, Michael Crump, John Kuruvilla