ImmunoGen Presents Findings from Newly Diagnosed Acute Myeloid Leukemia Cohorts in Phase 1b/2 Study of Pivekimab Sunirine in Combination with Azacitidine and Venetoclax at ASH - Seite 2

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 TP53^wt (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).

"Building upon our initial findings in frontline AML presented last year, these data show broad and consistent response rates in a larger study population and across major molecular subsets of interest, including those patients with biological mutations making them high-risk," said Michael Vasconcelles, MD, ImmunoGen's Executive Vice President, Research, Development, and Medical Affairs. "We are pleased with the low early mortality and manageable safety profile observed, in particular the lack of prolonged cytopenias. We look forward to continuing to expand our cohort of newly diagnosed unfit patients to inform the development path for pivekimab in AML.”