TY - JOUR
T1 - Imlunestrant, an oral selective estrogen receptor degrader, as monotherapy and combined with abemaciclib, in recurrent/advanced ER-positive endometrioid endometrial cancer
T2 - Results from the phase 1a/1b EMBER study
AU - Yonemori, Kan
AU - Boni, Valentina
AU - Min, Kim Gun
AU - Meniawy, Tarek M.
AU - Lombard, Janine
AU - Kaufman, Peter A.
AU - Richardson, Debra L.
AU - Bender, Laura
AU - Okera, Meena
AU - Matsumoto, Koji
AU - Giridhar, Karthik V.
AU - García-Sáenz, José Angel
AU - Prenen, Hans
AU - de Speville Uribe, Bernard Doger
AU - Dizon, Don S.
AU - Garcia-Corbacho, Javier
AU - Van Nieuwenhuysen, Els
AU - Li, Yujia
AU - Estrem, Shawn T.
AU - Nguyen, Bastien
AU - Bacchion, Francesca
AU - Ismail-Khan, Roohi
AU - Jhaveri, Komal
AU - Banda, Kalyan
N1 - Publisher Copyright:
© 2024
PY - 2024/12
Y1 - 2024/12
N2 - Objective: Imlunestrant is a next-generation oral selective estrogen receptor degrader designed to deliver continuous estrogen receptor (ER) target inhibition. EMBER is a phase 1a/b trial of imlunestrant, as monotherapy and combined with targeted therapy, in patients with ER+ advanced breast cancer or endometrioid endometrial cancer (EEC). This report focuses on patients with ER+ EEC. Methods: EMBER used an i3 + 3 dose-escalation design to determine the recommended phase 2 dose (RP2D) followed by dose-expansion cohorts (1:1 randomization): imlunestrant monotherapy and imlunestrant plus abemaciclib (150 mg twice daily). Eligible patients had measurable disease and progression or recurrence after platinum-containing chemotherapy. Prior fulvestrant or aromatase inhibitor was not allowed. Secondary endpoints included safety, pharmacokinetics and antitumor activity. Results: In total, 72 patients with a median of 2 prior anticancer therapies were treated. Among the 39 patients who received imlunestrant (400 mg [RP2D], n = 33; 800 mg, n = 6), the most common treatment-emergent adverse events (TEAEs) were grade 1–2 nausea (35.9 %), diarrhea (25.6 %), urinary tract infection (25.6 %), and abdominal pain (20.5 %). Overall response rate (ORR) was 10.3 %, clinical benefit rate (CBR) was 33.3 %, and median progression-free survival (mPFS) was 3.8 months (95 % CI, 1.8–6.7). Among the 33 patients who received imlunestrant (400 mg [RP2D], n = 29; 800 mg, n = 4) plus abemaciclib, the most common TEAEs were diarrhea (87.9 %), nausea (66.7 %), fatigue (48.5 %), and anemia (45.5 %). ORR was 18.2 %, CBR was 42.4 %, and mPFS was 6.8 months (95 % CI, 2.1–12). Conclusion: Imlunestrant, as monotherapy and combined with abemaciclib, has a manageable safety profile with preliminary evidence of antitumor activity in patients with ER+ EEC.
AB - Objective: Imlunestrant is a next-generation oral selective estrogen receptor degrader designed to deliver continuous estrogen receptor (ER) target inhibition. EMBER is a phase 1a/b trial of imlunestrant, as monotherapy and combined with targeted therapy, in patients with ER+ advanced breast cancer or endometrioid endometrial cancer (EEC). This report focuses on patients with ER+ EEC. Methods: EMBER used an i3 + 3 dose-escalation design to determine the recommended phase 2 dose (RP2D) followed by dose-expansion cohorts (1:1 randomization): imlunestrant monotherapy and imlunestrant plus abemaciclib (150 mg twice daily). Eligible patients had measurable disease and progression or recurrence after platinum-containing chemotherapy. Prior fulvestrant or aromatase inhibitor was not allowed. Secondary endpoints included safety, pharmacokinetics and antitumor activity. Results: In total, 72 patients with a median of 2 prior anticancer therapies were treated. Among the 39 patients who received imlunestrant (400 mg [RP2D], n = 33; 800 mg, n = 6), the most common treatment-emergent adverse events (TEAEs) were grade 1–2 nausea (35.9 %), diarrhea (25.6 %), urinary tract infection (25.6 %), and abdominal pain (20.5 %). Overall response rate (ORR) was 10.3 %, clinical benefit rate (CBR) was 33.3 %, and median progression-free survival (mPFS) was 3.8 months (95 % CI, 1.8–6.7). Among the 33 patients who received imlunestrant (400 mg [RP2D], n = 29; 800 mg, n = 4) plus abemaciclib, the most common TEAEs were diarrhea (87.9 %), nausea (66.7 %), fatigue (48.5 %), and anemia (45.5 %). ORR was 18.2 %, CBR was 42.4 %, and mPFS was 6.8 months (95 % CI, 2.1–12). Conclusion: Imlunestrant, as monotherapy and combined with abemaciclib, has a manageable safety profile with preliminary evidence of antitumor activity in patients with ER+ EEC.
KW - CDK4/6 inhibitors
KW - SERD
KW - Uterine cancer
UR - http://www.scopus.com/inward/record.url?scp=85207149213&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2024.10.006
DO - 10.1016/j.ygyno.2024.10.006
M3 - Article
C2 - 39442371
AN - SCOPUS:85207149213
SN - 0090-8258
VL - 191
SP - 172
EP - 181
JO - Gynecologic Oncology
JF - Gynecologic Oncology
ER -
