Publication
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
Journal Paper/Review - Aug 25, 2021
Jhaveri Komal, De Vita Serena, Crystal Adam, He Wei, Ji Yan, Balbin Alejandro, Sheng Qing, Kundamal Nicole, Huober Jens, Takahashi Shunji, Terret Catherine, Duhoux Francois P, Layman Rachel M, Cresta Sara, Yap Yoon-Sim, Juric Dejan, Curigliano Giuseppe
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
Brief description/objective
PURPOSE
Data are sparse for oral selective estrogen receptor (ER) degraders (SERDs) in cancer treatment. The investigational oral SERD LSZ102 was assessed in monotherapy and combination use in a phase I study.
MATERIALS AND METHODS
A phase I, multicenter, open-label dose-escalation study (NCT02734615) of LSZ102 alone (arm A; n=77) or with ribociclib (arm B; n=78) or alpelisib (arm C; n=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 (DLTs) in the first 28-day treatment cycle, adverse events (AEs), 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); 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% CI) were: arm A, 1.3% (0.0-7.0); arm B, 16.9% (9.3-27.1); 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.