TY - JOUR
T1 - A phase i study of LSZ102, an oral selective estrogen receptor degrader, with or without ribociclib or alpelisib, in patients with estrogen receptor-positive breast cancer
AU - Jhaveri, Komal
AU - Juric, Dejan
AU - Yap, Yoon Sim
AU - Cresta, Sara
AU - Layman, Rachel M.
AU - Duhoux, Francois P.
AU - Terret, Catherine
AU - Takahashi, Shunji
AU - Huober, Jens
AU - Kundamal, Nicole
AU - Sheng, Qing
AU - Balbin, Alejandro
AU - Ji, Yan
AU - He, Wei
AU - Crystal, Adam
AU - de Vita, Serena
AU - Curigliano, Giuseppe
N1 - Publisher Copyright:
© 2021 The Authors; Published by the American Association for Cancer Research
PY - 2021/11/15
Y1 - 2021/11/15
N2 - Purpose: Data are sparse for oral selective estrogen receptor (ER) degraders (SERD) in cancer treatment. The investigational oral SERD LSZ102 was assessed in monotherapy and combination use in a phase I study. Patients and Methods: A phase I, multicenter, open-label dose-escalation study (NCT02734615) of LSZ102 alone (arm A; n ¼ 77) or with ribociclib (arm B; n ¼ 78) or alpelisib (arm C; n ¼ 43) in heavily pretreated adults with histologically confirmed ER-positive breast cancer and prior disease progression. Arm A received LSZ102 200-900 mg/day; arm B, LSZ102 200-600 mg/day plus ribociclib 300-600 mg/day; arm C, LSZ102 300-450 mg/day plus alpelisib 200-300 mg/day. Key outcomes were dose-limiting toxicities (DLT) in the first 28-day treatment cycle, adverse events (AE), laboratory parameters, pharmacokinetics, biopsy ER protein, and investigator-assessed clinical response (RECIST v1.1). Results: The most common AEs were gastrointestinal. Treatment-related serious AEs occurred in 10% of participants (19/198), mostly in arm C [10/43 (23%)]. DLTs occurred in: arm A, 5% (4/77); arm B, 3% (2/78); and arm C, 19% (8/43). LSZ102 exposure was slightly greater than dose proportional. On-treatment biopsy ER reductions were observed, with a trend toward an LSZ102 dose response. Objective response rates (95% confidence interval) were: arm A, 1.3% (0.0-7.0); arm B, 16.9% (9.3-27.1); and arm C, 7.0% (1.5-19.1), and clinical benefit rates 7.8% (2.9-16.2), 35.1% (24.5-46.8), and 20.9% (10.0-36.0), respectively. Conclusions: LSZ102 was well tolerated alone and with ribociclib and had a manageable safety profile with alpelisib. Preliminary clinical activity was observed in combination use.
AB - Purpose: Data are sparse for oral selective estrogen receptor (ER) degraders (SERD) in cancer treatment. The investigational oral SERD LSZ102 was assessed in monotherapy and combination use in a phase I study. Patients and Methods: A phase I, multicenter, open-label dose-escalation study (NCT02734615) of LSZ102 alone (arm A; n ¼ 77) or with ribociclib (arm B; n ¼ 78) or alpelisib (arm C; n ¼ 43) in heavily pretreated adults with histologically confirmed ER-positive breast cancer and prior disease progression. Arm A received LSZ102 200-900 mg/day; arm B, LSZ102 200-600 mg/day plus ribociclib 300-600 mg/day; arm C, LSZ102 300-450 mg/day plus alpelisib 200-300 mg/day. Key outcomes were dose-limiting toxicities (DLT) in the first 28-day treatment cycle, adverse events (AE), laboratory parameters, pharmacokinetics, biopsy ER protein, and investigator-assessed clinical response (RECIST v1.1). Results: The most common AEs were gastrointestinal. Treatment-related serious AEs occurred in 10% of participants (19/198), mostly in arm C [10/43 (23%)]. DLTs occurred in: arm A, 5% (4/77); arm B, 3% (2/78); and arm C, 19% (8/43). LSZ102 exposure was slightly greater than dose proportional. On-treatment biopsy ER reductions were observed, with a trend toward an LSZ102 dose response. Objective response rates (95% confidence interval) were: arm A, 1.3% (0.0-7.0); arm B, 16.9% (9.3-27.1); and arm C, 7.0% (1.5-19.1), and clinical benefit rates 7.8% (2.9-16.2), 35.1% (24.5-46.8), and 20.9% (10.0-36.0), respectively. Conclusions: LSZ102 was well tolerated alone and with ribociclib and had a manageable safety profile with alpelisib. Preliminary clinical activity was observed in combination use.
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U2 - 10.1158/1078-0432.CCR-21-1095
DO - 10.1158/1078-0432.CCR-21-1095
M3 - Article
C2 - 34433648
AN - SCOPUS:85119011981
SN - 1078-0432
VL - 27
SP - 5760
EP - 5770
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 21
ER -