ImmunoGen, Inc. announced new safety and efficacy findings from the newly diagnosed (ND) cohorts of the Phase 1b/2 study of pivekimab sunirine (pivekimab) in combination with azacitidine (Vidaza®) and venetoclax (Venclexta®), (pivekimab triplet) in patients with ND acute myeloid leukemia (AML). These findings will be presented in a poster session at the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, California. In the open-label, multicenter, Phase 1b/2 study of pivekimab in combination with azacitidine and venetoclax in patients with ND CD123-positive AML, patients received the recommended Phase 2 dose of pivekimab at 0.045 mg/kg on day 7, azacitidine at 75 mg/m2 daily on days 1-7, and venetoclax at up to 400 mg for at least 14 days or up to 28 days, based on cohort assignment, in a 28-day cycle.

The primary endpoints are complete remission (CR) rate, composite CR rate (CCR [CR+CRh+CRp+CRi]), minimal residual disease (MRD) negativity rate, and duration of remission. Key secondary endpoints are safety, pharmacokinetics, and immunogenicity. Key findings for 50 ND patients (n=25 per cohort) as of September 29, 2023 (data cut-off) include: Anti-Leukemia Activity In the overall population, CCR rate was 68% (34/50), CR rate was 54% (27/50), and MRD negativity rate among evaluable patients achieving CCR was 76% (22/29).

MRD was assessed centrally by flow cytometry with <0.1% considered negative. Response rates and MRD negativity were numerically comparable between cohorts 1 and 2, despite differences in the venetoclax schedule. In a post hoc subset analysis of patients unfit for intensive chemotherapy (i.e. patients >75 years of age, and/or with pre-specified comorbidities) (n=23), CCR rate was 78% (18/23), CR rate was 61% (14/23), and MRD negativity rate was 79% (11/14).

In patients known to be TP53wt (n=25), CCR rate was 88% (22/25), CR rate was 84% (21/25), and MRD negativity rate was 80% (16/20). CCR and MRD negativity rates, respectively, were high across other major molecular subsets, including: FLT3 (ITD or TKD): 100% (6/6) and 100% (6/6), IDH1 mutant: 100% (4/4) and 67% (2/3), IDH2 mutant: 100% (6/6) and 83% (5/6), NPM1 mutant: 100% (8/8) and 86% (6/7), K/NRAS mutant: 50% (3/6) and 67% (2/3), TP53 mutant: 50% (7/14) and 50% (3/6). Among all MRD negative patients, the median time to MRD negativity was 1.87 months (range: 0.79-5.16 months).

Although follow-up duration was short (median 5.2 months), landmark overall survival estimate at 6 months is 86%. The study is continuing to enroll newly diagnosed unfit AML patients. Safety: The triplet displayed a manageable safety profile; no new safety signals were observed compared to previously reported data.

The most common non-hematologic treatment-emergent adverse events (TEAEs) (all grades [grade 3+]) seen in =20% of all patients were constipation (48% [2%]), peripheral edema (44% [4%]), diarrhea (40% [2%]), hypophosphatemia (34% [2%]), nausea (32% [4%]), hypokalemia (28% [4%]), fatigue (24% [6%]), hypotension (24% [2%]), and pyrexia (24% [0%]). In the overall population: Rates of cytopenias were similar to those observed with azacitidine and venetoclax, with a median neutrophil recovery to =500/µL and platelet recovery to =50,000/µL by day 34 and day 22, respectively. No veno-occlusive disease, capillary leak syndrome, or sinusoidal obstruction syndrome were observed.

Infusion-related reactions (IRRs) occurred in 16% of patients (0 grade 3+ IRRs). Discontinuations due to an adverse event (AE) were 4% (2 patients). 30-day mortality was 0%.

60-day mortality was 4% (2 patients; due to pneumonia and early disease progression).