First-in-human phase 1/2a study of the first-in-class, next-generation CDK4-selective inhibitor PF-07220060 + endocrine therapy (ET): Updated safety data in patients with HR+/HER2− mBC.

3108 Background: PF-07220060 is a novel, highly selective CDK4 inhibitor with significant CDK6 sparing. Preliminary data have been reported for the monotherapy dose-escalation cohort (Part 1A) and ET combination dose-finding cohorts (Parts 1B-C) in the first-in-human study of PF-07220060 in patients (pts) with advanced solid tumors (1). Herein, we report updated safety data for PF-07220060 + ET in pts with HR+/HER2− advanced/metastatic breast cancer (mBC), including extended follow-up data for pts in dose-finding cohorts (Parts 1B-C) and first disclosure of data for pts in dose-expansion cohorts (Parts 2B-C). Methods: In Parts 1B and 1C of this Phase 1/2a study (NCT04557449), PF-07220060 + ET (letrozole LET or fulvestrant FUL, respectively) was administered to pts with HR+/HER2− mBC as ≥2L therapy after prior CDK4/6 inhibitors (CDK4/6i). In dose-expansion cohort 2B, pts with HR+/HER2− mBC received 1L PF-07220060 + LET; in Part 2C, pts with progression after prior ET received PF-07220060 + FUL. Pts in Parts 2B-C were CDK4/6i-naïve. Primary objective was to evaluate safety and tolerability of PF-07220060 + ET. Results: At data cutoff (Nov 1, 2023), 33 pts received PF-07220060 (300 or 400 mg BID) + ET in Parts 1B-C; 34 pts in Part 2B and 36 pts in Part 2C received PF-07220060 (300 mg BID) with LET or FUL, respectively. Table summarizes patient characteristics in each cohort. In the pooled 1B-C cohort, the most common TEAEs were neutropenia (54. 5% 18. 2% G3), diarrhea (42. 4% 0% G3), and nausea (42. 4% 3. 0% G3). In Parts 2B-C, the most common TEAEs were neutropenia (61. 8%/36. 1% 23. 5%/11. 1% G3), leukopenia (38. 2%/33. 3% 0%/13. 9% G3), and anemia (23. 5%/27. 8% 0%/2. 8% G3). No >G3 TEAEs were reported in Parts 1B-C or 2B-C. In Parts 1B-C, 2B, and 2C, TEAEs leading to discontinuation were reported in 3. 0%, 5. 9%, and 8. 3% of pts, respectively; dose reductions due to AEs were reported in 12. 1%, 5. 9%, and 8. 3% of pts, respectively. Median (range) relative dose intensity (RDI) of PF-07220060 was 98. 3% (52. 5–100) in Parts 1B-C, 99. 8% (37. 2–100) in Part 2B, and 99. 7% (68. 6–100) in Part 2C. Conclusions: PF-07220060 + ET was well tolerated in pts with HR+/HER2− mBC across post-CDK4/6i and CDK4/6i-naïve cohorts. Incidence of G3 neutropenia and other TEAEs was low, enabling high RDI and potential for continuous target coverage. 1. Yap, et al. J Clin Oncol. 2023;41 (16ₛuppl): 3009. Clinical trial information: NCT04557449. Table: see text