KEY TAKEAWAYS
- The phase I/II trial aimed to assess the safety and tolerability of LNS8801 alone and in combination with pembrolizumab in mUM pts.
- The secondary endpoints include PK, PD, ORR, and DCR based on RECIST v1.1. criteria.
- The study found that LNS8801 was safe and effective in mUM pts alone or in combination with pembrolizumab.
LNS8801 is an oral drug that activates G-protein coupled estrogen receptor (GPER) and has anti-cancer effects. The drug is safe and tolerable in humans, with promising results in combination with immune checkpoint inhibitors(ICIs).
Researchers aimed to assess the safety and tolerability of LNS8801 alone and in combination with pembrolizumab in metastatic uveal melanoma (mUM) patients (pts).
Pts received LNS8801 (125 mg, QD, PO) alone or with pembrolizumab (200 mg, Q3W, IV). The primary objective was to assess safety and tolerability based on NCI CTCAE v5.0. Secondary endpoints included pharmacokinetics (PK), pharmacodynamics(PD), objective response rate (ORR), and disease control rate (DCR, CR+PR+SD) per RECIST v1.1. The presence of a consensus, fully functional, germline GPER coding sequence was evaluated via Sanger sequencing on DNA extracted from blood as a potential predictive biomarker.
About 15 pts received treatment of 8 with LNS8801 alone and 7 with a combination of LNS8801 and pembrolizumab, after a median of 2 prior systemic therapies. In the monotherapy group, 4 of 8 pts had potentially drug-related adverse events(AEs) (all grade 1), while in the combination group, 6 of 7 pts experienced potentially drug-related AEs (grades 1-2), with fatigue being the most common. Among the 14 pts evaluated for efficacy (7 mono, 7 combo), 7 achieved disease control (4 mono, 3 combo), resulting in a 50% DCR, and 1 patient in the combination group achieved a confirmed partial response. About 2 of 12 sequenced pts (1 mono, 1 combo) had a consensus germline GPER, and both showed ongoing disease control for more than 24 weeks.
The study found that LNS8801 was safe and effective in pts with mUM alone or in combination with pembrolizumab. Germline GPER mutations may be a target for mUM therapy.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.9543#
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04130516
Alexander Noor Shoushtari, Marya F. Chaney, Justine Vanessa Cohen, Tina Garyantes, Jessica Jiyeong Lin, Jeffrey Joseph Ishizuka, Alain C. Mita, Monica M. Mita, Carolyn Muller, Christopher Natale, Marlana M. Orloff, Kyriakos P. Papadopoulos, Sapna Pradyuman Patel, and Jordi Rodon Ahnert. DOI: 10.1200/JCO.2023.41.16_suppl.9543 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 9543-9543.
