51P - ctDNA analyses at baseline in patients with ER-positive (ER+), HER2-negative (HER2-) advanced breast cancer (aBC) treated with imlunestrant in the EMBER phase I study

Background

The EMBER trial (NCT04188548) demonstrated that the next generation oral SERD, imlunestrant, had favourable safety and pharmacokinetics profiles with a clinical benefit rate (CBR) of 42% in 114 patients (pts) with ER+, HER2- aBC. Here we explore the association between ctDNA results at baseline and CBR in pts treated with imlunestrant.

Methods

Baseline plasma samples from ER+, HER2- aBC pts treated with single agent imlunestrant (at doses ranging from 200-1200 mg QD) were sequenced using the Guardant360 assay. The association between ctDNA positivity and alterations at baseline with CBR (CR or PR, or stable disease ≥24 weeks) were assessed with the Fisher's test.

Results

At data cutoff (August 14, 2023), 109 pts had evaluable baseline plasma samples. Median number of prior therapies for aBC was 2 (range, 0-8), including: prior CDK4/6 inhibitor (93%), fulvestrant (52%), or chemotherapy (25%). Most pts (90%, 98/109) had detectable ctDNA at baseline, while 11 (10%) pts did not. Commonly altered genes included ESR1, PIK3CA, and TP53. In total, 43% of pts had an activating PI3K/AKT/PTEN pathway alteration and 20% had concomitant ESR1 and PIK3CA alterations. Overall, single agent imlunestrant achieved a CBR of 42% [95%CI 32 - 52] in pts (n=109) with evaluable samples. Subgroup analyses based on ctDNA results did not identify any significant difference in CBR across subgroups (Table). However, a numerically higher CBR was observed in pts (n=11) without baseline detectable ctDNA vs pts (n=98) with detectable ctDNA: 64% vs 40%, p = 0.2. D = Gene alteration detected, ND = Gene alteration not detected. Table: 51P

Conclusions

Exploratory ctDNA analyses of ER+, HER2- aBC pts treated with imlunestrant in the EMBER trial demonstrated no significant impact on clinical benefit in pts harboring common genomic alterations. These findings will be further explored in the ongoing phase III EMBER-3 trial.

Clinical trial identification

NCT04188548.

Editorial acknowledgement

All writing, editorial assistance, and statistical analysis were funded by Eli Lilly and Company. Medical writing and editorial support were provided by Aislinn Richardson, employee of Eli Lilly.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

C.X. Ma: Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Biovica, Olaris, Gilead Sciences, Pfizer, Lilly, Tempus, Genzyme, Tersera, Stemline Therapeutics, Dailchi Sankyo/AstraZeneca, Regor Therapeutics group ; Financial Interests, Personal, Other, Travel: SABCS, Total Health Conferencing ; Financial Interests, Personal, Other, patents, royalties, other intellectual property: UpToDate: Authorship . F.C. Bidard: Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, Lilly, Novartis, Menarini, Sanofi (Inst), GSK, Rain Oncology, Caris Life Sciences, GE Healthcare, Exact Sciences, Gilead Sciences, SAGA Diagnostics. P. Neven: Financial Interests, Personal, Advisory Role: AstraZeneca, Hoffman/La Roche, Eli Lilly and Company, Novartis, Pfizer, Pierre Fabre, Radius Health, Roche, and Teva; Financial Interests, Personal, Other, Travel: Eli Lilly and Company, Pfizer, and Roche; Financial Interests, Personal, Full or part-time Employment: Sanofi . S. Wander: Financial Interests, Personal, Advisory Role: Foundation Medicine, Puma Biotechnology, Veracyte, Lilly, Hologic, Pfizer, Biovica; Financial Interests, Personal, Speaker’s Bureau: Lilly, Guardant Health; Financial Interests, Personal, Funding: Genentech, Lilly, Pfizer, Regor Therapeutics, Nuvation Bio. S. Estrem: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. B. Nguyen: Financial Interests, Personal, Full or part-time Employment: Loxo/Lilly . R. Ismail-Khan: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company; Financial Interests, Personal, Advisory Role: Novartis . Y. Li: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company; Financial Interests, Personal, Other, Travel: Eli Lilly and Company. S. Young: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. V.S. Rodrik-Outmezguine: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company; Financial Interests, Personal, Stocks/Shares: Eli Lilly and Company. K. Jhaveri: Financial Interests, Personal, Advisory Board: Novartis, Phizer, AstraZeneca, Jounce therapeutics, Synthon, Intellisphere, Bristol Myers Squibb, Genentech, AbbVie, Lilly, Blueprint Medicines, Seagen, Biotheranostics, Sun Pharma Advanced Research Company, Taiho Oncology, Sanofi, Gilead Sciences, Scorpia; Financial Interests, Personal, Other, Travel: Taiho Pharmaceutical, Jounce Therapeutics, Pfizer, AstraZeneca, Intellisphere, Lilly, Gilead Sciences, Genentech/Roche; Financial Interests, Institutional, Research Grant: Novartis, Genentech, Debiopharm Group, ADC Therapeutics, Pfizer, Novita Pharmaceuticals, Clovis Oncology, Lilly, Zymeworks, Immunomedics, Puma Biotechnology, VelosBio/Merck, AstraZeneca, Context Therapeutics, Scorpion Therapeutics,Blueprint Medicines . All other authors have declared no conflicts of interest.