KEY TAKEAWAYS
- An interventional phase I trial aimed to analyze the expanded safety and efficacy data for INCB099280 in diverse advanced solid tumors, building on promising initial findings.
- The primary endpoints were safety, tolerability, and pharmacologically active/MTD determination.
- INCB099280 showed encouraging antitumor activity, warranting further exploration in solo and combo therapy for advanced solid tumors.
INCB099280 is an oral, small-molecule inhibitor of PD-L1, a protein cancer cell used to evade the immune system. By blocking PD-L1, INCB099280 may help the immune system recognize and attack cancer cells.
Hans Prenen and his research group spearheaded the study that aimed to update the safety, tolerability, and antitumor activity data of INCB099280 in a Phase 1 study for advanced solid tumors.
The study enrolled individuals aged ≥18 with ECOG PS ≤1, experiencing disease progression post-treatment or ineligible for/without access to standard treatment. In Part 1, INCB099280 doses were escalated from 100 mg QD using a Bayesian optimal interval design. Part 2 involved three expansion cohorts focusing on specific tumor types: 1) IO-naive patients, 2) IO-naive patients with MSI-H/dMMR tumors, and 3) patients who progressed on anti-PD-1 mAb.
The primary endpoints were safety, tolerability, and pharmacologically active/MTD determination for INCB099280. Additional analyses included pharmacokinetics, objective response rate(ORR) according to RECIST v1.1, and biomarkers of pharmacologic activity.
About 72 patients were administered INCB099280 at doses ranging from 100 mg QD to 800 mg BID. The median age was 63 years (range: 21–86), with 64.0% having received at least two prior lines of treatment. The most common tumor types were anal (14.5%), cervical (8.7%), and colorectal (7.6%).
Dosing was escalated to 800 mg BID, and the Maximum Tolerated Dose (MTD) was not reached. In Part 2, five dose levels were expanded to 800 mg BID. 137 patients (79.7%) discontinued treatment, with 69.2% citing disease progression as the reason. 95.3% of patients experienced at least one treatment-emergent adverse event (TEAE). A few patients exhibited complete responses, with high baseline tumor mutational burden scores (34–49 mut/Mb) and a 92.3% reduction in ctDNA levels at cycle 4 day 1/end of treatment. Updated results will be presented.
The results demonstrated overall favorable tolerability across all tested doses. Updated results revealed promising antitumor activity, supporting the potential future development of INCB099280, both as a monotherapy and in combination regimens, for treating advanced solid tumors. The research was sponsored by Incyte Corporation.
Source: https://cslide.ctimeetingtech.com/immuno23hybrid/attendee/confcal/show/session/34
Clinical Trial: https://clinicaltrials.gov/study/NCT04242199
Prenen H. ‘’A Phase 1 Study Exploring the Safety and Tolerability of the Small-Molecule PD-L1 Inhibitor INCB099280 in Select Advanced Solid Tumors.’’ Presented at ESMO I-O 2023, Geneva, Switzerland (Presentation Number 155P).
