Abstract P3-07-28: SERENA-1: Updated analyses from a Phase 1 study of the next generation oral selective estrogen receptor degrader camizestrant (AZD9833) combined with abemaciclib, in women with ER-positive, HER2-negative advanced breast cancer

Abstract

Abstract Background: SERENA-1 (NCT03616587) is a Phase 1, multi-part, open-label study of camizestrant in women with ER+/HER2− advanced breast cancer. Parts A/B and C/D (escalation/expansion) examined camizestrant as monotherapy and in combination with palbociclib respectively and have been presented previously.1,2 Here we present data from parts G/H which examined camizestrant in combination with abemaciclib. Methods: The primary objective was to determine the safety and tolerability of camizestrant 75 mg once daily (QD) in combination with abemaciclib 150 mg twice daily (BID). Secondary objectives included investigation of anti-tumor response and pharmacokinetics (PK). Participants were previously treated women of any menopausal status (pre-menopausal women received this combination alongside ongoing ovarian function suppressors). Prior treatment with ≤2 lines of chemotherapy in the advanced setting was permitted. There was no limit on the number of lines of prior endocrine treatment in the advanced setting; previous treatment with CDK4/6 inhibitors (CDK4/6i) and fulvestrant was permitted. Results: As of 1st June 2022, 24 patients had received camizestrant in combination with abemaciclib with a median 7.7 month follow up. Tolerability of the combination of camizestrant and abemaciclib was consistent with that of each drug individually. No patient required camizestrant dose reduction. All camizestrant-related heart rate decreases were Grade 1 (asymptomatic). PK data for camizestrant in combination with abemaciclib were consistent with camizestrant as monotherapy and published abemaciclib steady-state PK data, indicating no clinically relevant drug-drug interaction. In these heavily pre-treated patients (46% prior chemotherapy, 75% prior CDK4/6i, 54% prior fulvestrant; all in the advanced disease setting) and of whom 67% had visceral metastases, the objective response rate was 5/19 (26.3%), the clinical benefit rate at 24 weeks was 16/24 (66.7%) and the median progression-free survival had not been reached, with 8/24 patients experiencing a progression event. These data support the use of camizestrant 75 mg QD combined with the approved abemaciclib dose. Conclusions: Camizestrant 75 mg QD in combination with abemaciclib 150 mg BID was well tolerated with encouraging clinical activity. The inclusion of this regimen in the ongoing Phase 3, SERENA-6 trial 3, of camizestrant combined with CDK4/6i versus an aromatase inhibitor, will further clarify the role of this combination in the treatment of patients with ER+/HER2− advanced breast cancer with tumors expressing ESR1 mutations.