June 4, 2024
By Catlin Nalley
Imlunestrant, alone or in combination with abemaciclib, is a safe and tolerable treatment option for patients with metastatic estrogen receptor (ER)-positive endometrioid endometrial cancer, according to findings recently presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 5589).
“Imlunestrant is a next-generation oral selective estrogen receptor degrader designed to deliver continuous estrogen receptor target inhibition aimed to improve outcomes for patients with ER-positive cancers,” noted study author Kan Yonemori, MD, PhD, a lead principle investigator in the Department of Medical Oncology at the National Cancer Center Hospital in Tokyo, Japan, and colleagues.
“In the first-in-human, global, open-label, Phase Ia/Ib EMBER trial (NCT04188548), imlunestrant showed favorable safety, pharmacokinetics, and clinical benefit in pre-treated patients with ER-positive advanced breast cancer or endometrioid endometrial cancer.”
Below, updated imlunestrant monotherapy data and the first clinical data of imlunestrant plus abemaciclib in ER-positive endometrioid endometrial cancer patients from EMBER are discussed.
Eligible patients had ER-positive endometrioid endometrial cancer who were previously treated with, or deemed inappropriate for, platinum-containing chemotherapy, according to the study authors. Patients with prior fulvestrant or aromatase inhibitor therapy were not included in this analysis.
The primary objective was to determine the recommended Phase II dose (RP2D) of imlunestrant monotherapy and in combination. Key secondary endpoints included safety, tolerability, clinical benefit rate (CBR: best overall response of complete or partial response, or stable disease ≥24 weeks), disease control rate, overall response rate, and progression-free survival using RECIST v1.1. Exploratory objectives included the evaluation of biomarkers.
In Phase Ia, patients underwent treatment with imlunestrant alone. In Phase Ib, patients were randomized (1:1) to receive imlunestrant alone or in combination with abemaciclib. Plasma samples were collected at baseline for all patients and at Cycle 2 (for monotherapy patients) for ctDNA analysis to correlate with clinical benefit. The data cutoff date was August 14, 2023.
Overall, the study included 72 patients. Of those, 39 patients received imlunestrant alone (33 at 400 mg [RP2D] and 6 at 800 mg po daily) and 33 patients received imlunestrant (29 at 400 mg and 4 at 800 mg po daily) plus abemaciclib (150 mg po twice daily).
Among patients who received monotherapy, the most common treatment-emergent adverse events (all grade/Grade 3) were nausea (36%, 3%), diarrhea (26%, 0), urinary
tract infection (26%, 3%), and abdominal pain (21%, 8%), according to the investigators. For imlunestrant + abemaciclib, the most common TEAEs (all grade/Grade 3) included diarrhea (88%, 3%), nausea (67%, 0), fatigue (49%, 9%), and anemia (46%,12%). In the monotherapy arm, data showed that patients with deeper (≥50%) declines
in ctDNA variant allele frequency had a higher CBR (4/7 vs. 4/17).
“Overall rates of aberrant p53 expression, TP53 mutation, and MSI were low in FFPE specimens and baseline ctDNA samples,” the study authors noted, while also highlighting that “archival tumor samples were less likely to show alterations in comparison to baseline ctDNA samples.
“Imlunestrant, as a monotherapy or with abemaciclib, appears safe and tolerable with preliminary evidence of efficacy in patients with metastatic ER-positive endometrioid endometrial cancer,” concluded Yonemori and colleagues. “In the monotherapy arm, patients who achieved a molecular response had greater clinical benefit and longer progression-free survival.”
Catlin Nalley is a contributing writer.