Lerociclib (G1T38), a continuously dosed oral CDK4/6 inhibitor, with fulvestrant in HR+/HER2-advanced breast cancer patients: Updated phase II results and dose selection
Arkenau, H. T.
Baird, R. D.
Wardley, Andrew M
Wolfgang, C. D.
Beelen, A. P.
AffiliationInstitute of Oncology, Arensia Exploratory Medicine Research Unit, Chisinau, Moldova;
MetadataShow full item record
AbstractBackground: CDK4/6 inhibitors (CDK4/6i) combined with fulvestrant (F) are the established standard of care for HR+/HER2- advanced breast cancer (ABC). Two of the three approved CDK4/6i cause dose-limiting neutropenia requiring a drug holiday, and the third is limited by gastrointestinal (GI) toxicity. Lerociclib is a potent, selective CDK4/6i that is dosed continuously. Initial data presented at SABCS 2019 indicated that lerociclib + F had low rates of GI toxicity and Grade 4 neutropenia, and antitumor activity was comparable with other CDK4/6i + F combinations. Methods: This phase I/II study assessed lerociclib with 500 mg F in patients (pts) with HR+/HER2- ABC that had progressed following endocrine therapy. Up to 2 prior chemotherapies in the advanced setting in phase I (dose escalation), and 1 prior in phase II (dose expansion) were allowed. Prior F and CDK4/6i exposure were excluded in phase II. The objectives were to evaluate DLTs, safety, tolerability, PK, preliminary efficacy, and determine the recommended dose of lerociclib when combined with F for future randomized trials. Results: As of Jan 31, 2020, 110 pts had been enrolled across doses of 200e650 mg once daily and 100e250 mg twice daily (BID). Twenty pts received 150 mg BID for a median 6.9 (range 1.7e27.8) months, with median age of 55 years (range 33e84), ECOG of 0 (85%), and median 1 line (range 0e5) of prior anticancer therapy in the advanced setting. The most common lerociclib-related AEs at 150 mg BID were neutropenia (55%), leukopenia (40%), diarrhea (20%), and anemia (20%). Rates of Grade 3 and 4 neutropenia were 30% and 5%, respectively. There were no reports of Grade 3 nausea, vomiting, or diarrhea. Nineteen pts at 150 mg BID were evaluable for tumor response based on RECIST version 1.1. Six pts (32%) had a confirmed PR; 9 (47%) had SD; 4 (21%) had PD. The CBR (CR+PR+SD 24 weeks) was 74% (14/19).Subgroup analyses revealed that pts who received no prior chemotherapy in the advanced setting (9/19 pts) had the highest CBR of 89%. Conclusions: Lerociclib 150 mg BID dosed continuously demonstrated a differentiated profile with low rates of GI toxicity and Grade 3/4 neutropenia. Efficacy compares favorably to approved CDK4/6i + F combinations.
CitationBulat I, Maglakelidze M, Krastev B, Arkenau HT, Murias C, Baird RD, et al. 334P Lerociclib (G1T38), a continuously dosed oral CDK4/6 inhibitor, with fulvestrant in HR+/HER2- advanced breast cancer patients: Updated phase II results and dose selection. Annals of Oncology. 2020;31:S380-S.
JournalAnnals of Oncology
TypeMeetings and Proceedings