Phase I/Ib Trial of Inavolisib Plus Palbociclib and Endocrine Therapy for PIK3CA-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced or Metastatic Breast Cancer.
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Embargo End Date
ICR Authors
Authors
Jhaveri, KL
Accordino, MK
Bedard, PL
Cervantes, A
Gambardella, V
Hamilton, E
Italiano, A
Kalinsky, K
Krop, IE
Oliveira, M
Schmid, P
Saura, C
Turner, NC
Varga, A
Cheeti, S
Hilz, S
Hutchinson, KE
Jin, Y
Royer-Joo, S
Peters, U
Shankar, N
Schutzman, JL
Juric, D
Accordino, MK
Bedard, PL
Cervantes, A
Gambardella, V
Hamilton, E
Italiano, A
Kalinsky, K
Krop, IE
Oliveira, M
Schmid, P
Saura, C
Turner, NC
Varga, A
Cheeti, S
Hilz, S
Hutchinson, KE
Jin, Y
Royer-Joo, S
Peters, U
Shankar, N
Schutzman, JL
Juric, D
Document Type
Journal Article
Date
2024-11-20
Date Accepted
Abstract
PURPOSE: To investigate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of inavolisib, a potent and selective small-molecule inhibitor of p110α that promotes the degradation of mutated p110α, in combination with palbociclib and endocrine therapy (ET), in a phase I/Ib study in patients with PIK3CA-mutated, hormone receptor-positive/human epidermal growth factor receptor 2-negative locally advanced/metastatic breast cancer (ClinicalTrials.gov identifier: NCT03006172). METHODS: Women ≥18 years of age received inavolisib, palbociclib, and letrozole (Inavo + Palbo + Letro arm) or fulvestrant (Inavo + Palbo + Fulv arm) until unacceptable toxicity or disease progression. The primary objective was to evaluate safety or tolerability. RESULTS: Fifty-three patients were included, 33 in the Inavo + Palbo + Letro arm and 20 in the Inavo + Palbo + Fulv arm. Median duration of inavolisib treatment was 15.7 and 20.8 months (cutoff: March 27, 2023), respectively. Treatment-related adverse events (TRAEs) occurred in all patients; the most frequent were stomatitis, hyperglycemia, and diarrhea; grade ≥3 any TRAE rates were 87.9% and 85.0%; 6.1% and 10.0% discontinued any treatment due to TRAEs in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. No PK drug-drug interactions (DDIs) were observed among the study treatments when administered. Confirmed objective response rates were 52.0% and 40.0% in patients with measurable disease, and median progression-free survival was 23.3 and 35.0 months in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. Available paired pre- and on-treatment tumor tissue and circulating tumor DNA analyses confirmed the effects of study treatment on pharmacodynamic and pathophysiologic biomarkers of response. CONCLUSION: Inavolisib plus palbociclib and ET demonstrated a manageable safety profile, lack of DDIs, and promising preliminary antitumor activity.
Citation
Journal of Clinical Oncology, 2024, 42 (33), pp. 3947 - 3956
Source Title
Journal of Clinical Oncology
Publisher
LIPPINCOTT WILLIAMS & WILKINS
ISSN
0732-183X
eISSN
1527-7755
Collections
Research Team
Molecular Oncology