Abstract 212P
Background
Palazestrant is a small molecule oral complete ER antagonist (CERAN) and selective ER degrader (SERD) that completely blocks ER-driven transcriptional activity. Palazestrant combined with ribociclib demonstrated activity in both ESR1-wt and ESR1-mut models, and in brain metastasis animal models. In a phase 1/2 monotherapy study of ER+, HER2- metastatic breast cancer (MBC) patients (pts), palazestrant was well tolerated, demonstrated encouraging antitumor efficacy and favorable pharmacokinetics (PK) at the 120 mg once daily (qd) recommended phase II dose (Lin et al. ESMO 2023 MO382). This study evaluates the safety, PK, and antitumor activity of palazestrant plus ribociclib in pts with ER+, HER2– MBC (NCT05508906).
Methods
Pts with evaluable ER+, HER2– advanced or MBC with ≤2 prior endocrine therapies (prior CDK4/6 inhibitors [CDK4/6i] allowed) and ≤1 prior line of chemotherapy were included. Patients received palazestrant at 30, 60, or 120 mg qd in combination with ribociclib (600 mg qd on a 3-weeks-on, 1-week-off schedule).
Results
As of January 02, 2024, 33 pts were on study for ≥4 weeks, 27 pts received 120 mg palazestrant. Twenty-seven pts (82%) received prior CDK4/6i: 24 prior palbociclib, 5 prior ribociclib and 4 prior abemaciclib; 7 pts (21%) received two prior lines of CDK4/6i. At time of the data cutoff, 26 pts (79%) were on treatment. The most common (≥25%) treatment-emergent adverse events (TEAEs) were nausea, neutropenia (G4: 2 pts; 6%), WBC count decreased, fatigue, anemia, and diarrhea. Most TEAEs were grade 1-2 and consistent with the known safety profiles of each drug. Tumor response and prolonged disease stabilization, including in those with prior CDK4/6i, were reported at time of data cutoff. No effect of palazestrant on ribociclib PK and no meaningful effect of ribociclib on palazestrant PK were observed, consistent with previously reported data.
Conclusions
Palazestrant plus ribociclib was well tolerated and enrollment is ongoing. No new safety signals were identified. Antitumor activity and clinical benefit, including in heavily pretreated patients, were observed. Updated data will be presented.
Clinical trial identification
NCT05508906.
Legal entity responsible for the study
The authors.
Funding
Olema Oncology.
Disclosure
V.F. Borges: Financial Interests, Personal, Other, Funding to me paid for other KOL meetings/consultation/Ad board faculty: Seagen; Financial Interests, Personal, Advisory Board, Funds paid to me through my institution for KOL consultation/Ad Boards: AstraZeneca; Financial Interests, Personal, Other, Funding paid to me through my institution for KOL/consulting: Gilead; Financial Interests, Personal, Invited Speaker, Funds provided to me for travel to ESMO Breast 2024 to present data on an ongoing clinical trial: Olema; Financial Interests, Personal and Institutional, Invited Speaker, Steering committee Chair for Her2Climb-02 and also research support for clinical trials paid to my institution: Seagen; Financial Interests, Institutional, Invited Speaker, Research Support paid to my institution for clinical trials: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Research support paid to my institution for clinical trials: Gilead; Financial Interests, Institutional, Invited Speaker, Research support to my institution for clinical trial: OncoSec, Olema, Agendia. J.A. Mouabbi: Financial Interests, Personal, Invited Speaker: BostonGene; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Gilead; Financial Interests, Institutional, Invited Speaker: BMS. C.X. Ma: Financial Interests, Personal, Advisory Board: Agendia, Bayer Healthcare Pharmaceuticals, Eli Lilly & Co., Sanofi - Genzyme, RayzeBio Inc.; Financial Interests, Personal, Advisory Board, Also Consulting Services: AstraZeneca Pharmaceuticals LP; Financial Interests, Personal, Other, Consulting Services - review data for oral paclitaxel: Athenex; Financial Interests, Personal, Invited Speaker: Guardant Health, PlusOne Health GmbH; Financial Interests, Personal, Advisory Board, And Consulting Services: Novartis Pharma AG, Olaris Inc., Tempus; Financial Interests, Personal, Other, Consulting Services: Pfizer, Seattle Genetics Inc., Sermonix Pharmaceuticals; Financial Interests, Personal, Royalties, Authorship Royalties, co-author: UptoDate; Financial Interests, Personal and Institutional, Invited Speaker: Pfizer Inc.; Non-Financial Interests, Other, Consulting Services: Medical Pharma Services Inc. A.R. Tan: Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals, Stemline Therapeutics, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Genentech/Roche, Merck, Arvinas; Non-Financial Interests, Leadership Role: ASCO Tapur Publications Committee. L. Sun, D. Faltaos, M. Tonda: Financial Interests, Personal, Full or part-time Employment: Olema Oncology. N.U. Lin: Financial Interests, Personal, Advisory Board, Ad board participation: Seattle Genetics, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Ad board/Steering Committee participation; consultant: AstraZeneca; Financial Interests, Personal, Advisory Board, Ad board/Steering committee participation; travel support: Olema Pharmaceuticals; Financial Interests, Personal, Other, Consultant: Blueprint Medicines, Janssen; Financial Interests, Personal, Other, High level Consulting: Artera Inc.; Financial Interests, Personal, Other, Steering committee: Stemline/Menarini; Financial Interests, Personal, Royalties, Royalties for book chapter(s): Up to Date; Financial Interests, Institutional, Funding, Trial funding to institute (and steering committee): Olema Pharmaceuticals, AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Funding, Trial funding to institute: Zion Pharmaceuticals; Financial Interests, Institutional, Funding, trial funding to institute: Pfizer, Genentech. All other authors have declared no conflicts of interest.