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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
Bulat, I. Maglakelidze, M. Krastev, B. Arkenau, H. T. Murias, C. Baird, R. D. Roylance, R. Crijanovschi, A. Gogiladze, M.
Bulat, I.
Maglakelidze, M.
Krastev, B.
Arkenau, H. T.
Murias, C.
Baird, R. D.
Roylance, R.
Crijanovschi, A.
Gogiladze, M.
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Abstract
Background: 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.
Description
Date
2020
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Keywords
Type
Meetings and Proceedings
Citation
Bulat 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.