184MO - First-in-human phase I/IIa study of the first-in-class, next-generation CDK4-selective inhibitor PF-07220060 in combination with endocrine therapy (ET) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC) who progressed on prior CDK4/6 inhibitors (CDK4/6i): Safety and efficacy update

Background

PF-07220060 is a novel potent oral CDK4i with significant sparing of CDK6. Preliminary safety and dose escalation data from this phI/IIastudy were previously presented. Here we report updated safety and efficacy data in pts with HR+/HER2− mBC, who progressed on prior CDK4/6i and ET, treated with PF-07220060 + ET.

Methods

This study in pts with advanced solid tumors was enriched for pts with HR+/HER2− mBC who received ≥2 lines of treatment including ET and CDK4/6i. Prior fulvestrant and chemotherapy were allowed. Study objectives were to assess safety, tolerability, and antitumor activity of PF-07220060 alone and in combination with ET.

Results

At data cutoff (Nov 1, 2023), 33 pts received PF-07220060 (300mg/400mg BID) in combination with letrozole or fulvestrant (Parts 1B + 1C). Median age was 62.0y (range 41–82); ECOG PS was 0 (36.4%) or 1. Median prior lines of systemic therapy (advanced setting) was 4.0 (range 1–11). All pts had prior CDK4/6i treatment, 24 (72.7%) had prior fulvestrant, and 22 (66.7%) had prior chemotherapy in the advanced/metastatic setting. Most frequent treatment-emergent adverse events (TEAEs) were neutropenia (54.5%; 18.2% Grade 3 [G3]), diarrhea (42.4%; 0% G3), and nausea (42.4%; 3.0% G3), with no >G3 TEAEs. Dose modifications due to TEAEs included: 1 (3.0%) pt discontinued PF-07220060, 5 (15.2%) pts had dose reduction, and 10 (30.3%) pts had dose interruptions. In 25 pts with measurable disease who progressed on prior CDK4/6i + ET, 8 (32.0%) had confirmed RECIST v1.1 objective responses (1 CR, 7 PR). Clinical benefit response (CR, PR, or ≥24 wks stable disease) was seen in 20/33 (60.6%) pts. Median progression-free survival was 8.1 months (95% CI: 5.3, 10.9). Confirmed objective responses (PRs) were observed irrespective of ESR1 or PI3K pathway mutations.

Conclusions

PF-07220060 + ET showed a favorable safety profile with few hematologic adverse events and infrequent dose modifications, and promising efficacy despite prior CDK4/6i treatment, irrespective of key mutations.

Clinical trial identification

NCT04557449.

Editorial acknowledgement

Medical writing support, conducted in accordance with the International Committee of Medical Journal Editors (ICMJE) guidelines, was provided by Kathleen Richter, PhD and Rachel C. Brown, PhD of Oxford PharmaGenesis, Inc., Newtown, PA.

Legal entity responsible for the study

Pfizer, Inc.

Funding

Pfizer Inc.

Disclosure

T.A. Yap: Financial Interests, Personal, Other, Consultant: Almac, Aduro, AstraZeneca, Atrin, Axiom, Bayer, Bristol Myers Squibb, Clovis, Cybrexa, EMD Serono, Guidepoint, Ignyta, I-Mab, Janssen, Merck, Pfizer, Repare, Roche, Schrodinger, Varian, Zai Labs, AbbVie, Acrivon, Adagene, Amphista, Artios, Athena, Avoro, Baptist Health Systems, BeiGene, Boxer, C4 Therapeutics, Calithera, Cancer Research UK, Diffusion, F-Star, Genmab, Glenmark, GLG, Globe Life Sciences, GSK, Idience, ImmuneSensor, Institut Gustave Roussy, Intellisphere, Kyn, MEI Pharma, Mereo, Natera, Nexys, Novocure, OHSU, OncoSec, Ono Pharma, Pegascy, PER, Piper-Sandler, Prolynx, resTORbio, Theragnostics, Versant, Vibliome, Xinthera, ZielBio, Radiopharm Theranostics, Sanofi, CUHK Committee, Ellipses.Life, LRG1, Panangium, Pliant Therapeutics, Seagen, Synthis, Tessellate Bio, TD2 Theragonostics, Tome Biosciences, Zentalis; Financial Interests, Personal, Other, University of Texas MD Anderson Cancer Center, where I am Medical Director of the Institute for Applied Cancer Science, which has a commercial interest in DDR and other inhibitors (IACS30380/ART0380 was licensed to Artios): MD Anderson Cancer Center, Institute for Applied Cancer Sciences; Financial Interests, Personal, Stocks/Shares: Seagan; Financial Interests, Institutional, Other, Grant/Research support: Bayer, Cyteir, EMD Serono, GSK, Karyopharm, Pfizer, Repare, Sanofi, Artios, AstraZeneca, BeiGene, BioNTech, Blueprint, BMS, Clovis, Constellation, Eli Lilly, Forbius, F-Star, Genentech, Haihe, ImmuneSensor, Ionis, Ipsen, Jounce, KSQ, Kyowa, Merck, Mirati, Novartis, Ribon Therapeutics, Regeneron, Rubius, Scholar Rock, Seattle Genetics, Tesaro, Vivace, Acrivon, Zenith; Financial Interests, Institutional, Other, Grant/Research Support: Acrivon; Financial Interests, Institutional, Research Grant: Boundless Bio, Ideaya. M.R. Sharma: Financial Interests, Personal, Other, Research funding/grant support: AbbVie, Adcentrx Therapeutics, Agenus, Alkermes, Alpine Immune Sciences, ALX Oncology, Artios, Astellas Pharma, AstraZeneca, Black Diamond Therapeutics, Boehringer Ingelheim, Bolt Biotherapeutics, Boundless Bio Therapeutics, Bristol Myers Squibb, Celgene. E.P. Hamilton: Financial Interests, Personal, Other, Research funding/grant support: AbbVie, Accutar Biotech, Acerta Pharma, ADC Therapeutics, Akeso Biopharma, Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond Therapeutics, Bliss Biopharmaceutical, Boehringer Ingelheim, Bristol Myers Squibb, Cascadia. P. Lorusso: Financial Interests, Personal, Other, Research funding/grant support: Genentech; served as consultant for AbbVie, ABL Bio, Actuate Therapeutics, Agenus, Amgen, AstraZeneca, Atreca, BAKX Therapeutics, Boehringer Ingelheim, Compass Therapeutics, Cullinan Oncology, DAAN Biotherapeutics, EMD Serono, GSK, I-Mab, ImCh. C. Basu, M. Delioukina, F. Liu, H. Neumann, J. Park: Financial Interests, Personal, Stocks/Shares: Pfizer Inc; Financial Interests, Personal, Full or part-time Employment: Pfizer Inc. A. Giordano: Financial Interests, Personal, Other, Consultant: Pfizer Inc.