ALL-440: Promising Safety and Efficacy Results from an Ongoing Phase 1/2 Study of Pembrolizumab in Combination with Blinatumomab in Patients (pts) with Relapsed or Refractory (R/R) Acute Lymphoblastic Leukemia (ALL)

Abstract

<h3>Background:</h3> Blinatumomab, a bispecific anti-CD19/CD3 antibody, demonstrated single-agent efficacy with 42% CR/CRh in R/R B-ALL. Upregulation of immune inhibitory molecules has been shown to confer resistance to blinatumomab. Here, we set out to test the combination of pembrolizumab and blinatumomab in a phase 1/2 trial (NCT03512405). <h3>Methods:</h3> Pts [≥18 years old (yo); ECOG <1] with CD19+ R/R B-ALL received blinatumomab 9 mcg/day on days 1–7 and 28 mcg/day on days 8–28 in cycle 1 and on days 1–28 in subsequent cycles. Pembrolizumab was given on day 15 (schedule A) or day 22 (schedule B) in cycle 1 and on days 1 and 22 in subsequent cycles. Cycle length was 42 days, except 35 days for cycle 1 in schedule A. We completed the schedule A phase 1 portion with primary objectives of safety, tolerability, and recommended phase 2 dose (RP2D) using the "3+3" design. <h3>Results:</h3> As of February 1, 2021, 7 pts were enrolled to phase 1, with one unevaluable. Six treated and evaluable pts received a median of 2 (1–5) cycles of treatment. At baseline, the median age was 51 yo (29–74) with median 2 (2–4) prior lines of regimens and median 29% (0–83) BM blasts. Two pts had extramedullary disease. In cycle 1, all 6 pts experienced grade (gr) 1–2 cytokine release syndrome. Neurologic toxicities were all reversible with only 1 ≥ gr3 AE. All-non-hematologic gr3 toxicities, were reversible. No dose-limiting toxicity, ≥ gr4 non-hematologic toxicity, or treatment-related deaths were seen. Five of 6 evaluable pts (83%) achieved MRD-negative CR after a median of 1 (1–2) cycle. Three pts in CR received alloHCT, all engrafted. With a median follow-up of 2.8 (1.1–9.6) months, 4 CRs are ongoing (1 post-transplant), and 5 of 6 pts are still alive at the data cut-off. <h3>Conclusions:</h3> The combination of pembrolizumab and blinatumomab in phase 1 of this study in pts with B-ALL was deemed safe with a manageable side effect profile and encouraging anti-leukemic activity. The study is now open for phase 2 with the primary objective of overall response rate.