364P - Elacestrant in combination with abemaciclib in patients (pts) with brain metastasis (mets) from estrogen receptor-positive (ER+), HER2-negative (HER2-) breast cancer: Preliminary data from ELECTRA, an open-label, multicenter, phase Ib/II study

Background

Endocrine therapy plus a CDK4/6 inhibitor (ET+CDK4/6i) is the mainstay in 1^st-line ER+, HER2- mBC; however, tumors often develop resistance. In EMERALD, single-agent elacestrant was associated with significantly prolonged PFS with manageable safety vs standard-of-care (SOC) ET in pts with ER+, HER2-, ESR1-mut mBC previously treated with ET+CDK4/6i (HR = 0.55; 95% CI, 0.39-0.77; P = 0.0005) (Bidard, 2022), resulting in the first oral SERD approved. The rationale for ELECTRA (NCT05386108) is to combine elacestrant + abemaciclib to overcome additional resistance mechanisms, improve efficacy, and enable an all-oral treatment option that can delay chemotherapy-based regimens, including ADCs.

Methods

Eligible pts have ER+, HER2- mBC. For phase 1b, brain mets are not required. For phase 2, the presence of ≥1 active and measurable brain mets per RECIST v1.1 is required. In the mBC setting, pts must have previously received ≥1 ET, ≤2 chemotherapy regimens, and 0-2 prior CDK4/6i (excluding abemaciclib). Phase 1b primary objective is to determine the recommended phase 2 dose (RP2D) of elacestrant + abemaciclib. Phase 2 will evaluate the efficacy and safety of the combination in pts with brain mets as both compounds have also been shown to cross the BBB (Conlan, 2020; Tolaney, 2020).

Results

As of April 2024, 27 pts were enrolled in phase 1b, none with brain mets. The most common all-grade AEs at the selected RP2D (elacestrant 345 mg QD + abemaciclib 150 mg BID) are shown in Table. No Grade 4 AEs or Grade 3 diarrhea were observed. Updated safety will be reported. Table: 364P

Treatment-emergent adverse events (≥35%) at the RP2D

Conclusions

The elacestrant + abemaciclib combination shows a manageable/predictable safety profile and favorable efficacy. Elacestrant has the potential to become the ET backbone for combination regimens. The Phase 2 portion of the study is currently enrolling.

Clinical trial identification

NCT05386108.

Editorial acknowledgement

Editorial assistance was provided by Mark Phillips, PharmD, MBA of The Phillips Group Oncology Communications, Inc.

Legal entity responsible for the study

Menarini Group.

Funding

Menarini Group.

Disclosure

E.M. Ciruelos: Financial Interests, Personal, Other, Speakers Bureau. Educational activities: Roche; Financial Interests, Personal, Invited Speaker, Symposia and Educational activities: Roche; Financial Interests, Personal, Advisory Board, Non-permanent advisor: Roche, Lilly, Novartis, Pfizer, Daiichi Sankyo, MSD; Financial Interests, Personal, Invited Speaker, Symposia and Education: Lilly; Financial Interests, Personal, Invited Speaker, Educational activities: Pfizer; Financial Interests, Personal, Advisory Board, Non-permanent advisor, Travel accommodation: AstraZeneca; Financial Interests, Personal, Other, Advisory Board: Gilead; Financial Interests, Personal, Other, Advisory Board, Invited speaker: Seagen; Financial Interests, Institutional, Funding, PI for Patricia 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for Prometeo 2 trial (sponsor: SOLTI Group): Pfizer; Financial Interests, Institutional, Funding, PI for TATEN trial (sponsor: SOLTI Group): MSD; Financial Interests, Institutional, Funding, PI for ATREZZO trial (sponsor: SOLTI Group): Roche; Non-Financial Interests, Member of Board of Directors, Non-profit organization dedicated to breast cancer research: SOLTI Cooperative Group; Non-Financial Interests, Advisory Role, Scientific Evaluator at ISCIII (Spanish Government Academic Research Platform): Instituto de Salud Carlos III. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, Olema Pharmaceuticals, Stemline Therapeutics, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Tubulis, Verascity Science, Theratechnologies; Financial Interests, Institutional, Other, Consulting: Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Jefferies LLC, Medical Pharma Services, Tempus Labs, Zentalis Pharmaceuticals; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Dana Farber Cancer Inst, Hutchinson MediPharma, MedImmune, Seagen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, Abbvie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses Pharma, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Artios, BeiGene, Bliss BioPharmaceuticals, Cascadian Therapeutics, Context Therapeutics, Cullinan, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Tolmar, Torque Therapeutics; Financial Interests, Institutional, Local PI: Bristol-Myers Squibb, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetic Laboratories, Silverback Therapeutics, Stemline Therapeutics. S. Kim: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Lilly, DaeHwa Pharma, ISU Abx, Daiich-Sankyo, BeiGene, Samsung Bioepics, OBI pharma; Financial Interests, Personal, Invited Speaker: Legochem Bioscience; Financial Interests, Personal, Ownership Interest: Genopeaks; Financial Interests, Institutional, Research Grant: Novartis, Sanofi-Genzyme, DongKook Pharm Co. E. Segui Solis: Financial Interests, Personal, Invited Speaker: Novartis, Veracyte, Pfizer, Daiichi Sankyo, Eisai; Financial Interests, Personal, Advisory Board: Pfizer, Seagen; Financial Interests, Personal, Full or part-time Employment: SOLTI; Financial Interests, Personal, Research Grant: Amgen. J. Á. García Saenz: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, AstraZeneca, Lilly, Daiichi Sankyo/AstraZeneca, Gilead Sciences, Seattle Genetics; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Institutional, Research Funding: AstraZeneca; Financial Interests, Personal, Other, Travel: Roche, Novartis. A. Di Sanzo: Financial Interests, Personal, Full or part-time Employment: Menarini Group. M. Domínguez Lizarbe: Financial Interests, Personal, Full or part-time Employment: Menarini Group. T. Wasserman: Financial Interests, Personal, Full or part-time Employment: Menarini Group. K.P. Theall: Financial Interests, Personal, Full or part-time Employment: Menarini Group. All other authors have declared no conflicts of interest.