134P - A Phase 1 Study Exploring the Safety and Tolerability of the Small Molecule PD-L1 Inhibitor INCB099318 in Select Advanced Solid Tumors

Background

INCB099318, an oral, programmed death ligand-1 (PD-L1) inhibitor, has shown preliminary efficacy and acceptable safety in an ongoing, Phase 1, open-label, multicenter study in patients with advanced solid tumors (Pinato, et al. SITC 2022). Here we present updated study results.

Methods

Eligible patients were ≥18 years with ECOG PS ≤1, who had disease progression after available treatment or were ineligible for/without access to standard treatment. In Part 1, doses were escalated from 100 mg BID using a Bayesian optimal interval design. Select doses were to be expanded in Part 2. Primary endpoints are INCB099318 safety, tolerability, and determination of pharmacologically active/maximum tolerated dose (MTD). Secondary and exploratory endpoints include pharmacokinetics, objective response rate per RECIST v1.1, and biomarkers of pharmacologic activity. Table: 134P

Safety

Results

As of June 23, 2023, 101 patients had received INCB099318 at doses from 100 to 800 mg QD or BID (Part 1, n=64; Part 2, n=37). Median age was 58 years (range, 29-89), 59.4% were women, 86.1% were White, 68.3% had ≥2 prior lines of treatment, and 9.9% had prior IO. Most common tumor types were cervical (17.8%), ovarian (10.9%), and colorectal (5.9%). No dose-limiting toxicities were observed and MTD was not reached. In Part 2, 3 dose levels were expanded (400 mg BID, n=18; 800 mg BID n=14, 800 mg QD, n=5). Overall, 82 patients (81.2%) discontinued treatment, 69 (68.3%) due to disease progression. 94 (93.1%) patients had treatment-emergent adverse events (TEAEs) (Table). Several responses have been observed, and updated results will be presented.

Conclusions

INCB099318 was generally well tolerated at all doses tested. Preliminary safety and response outcomes support future development of INCB099318 for the treatment of select advanced solid tumors.

Clinical trial identification

NCT04272034.

Editorial acknowledgement

Editorial assistance was provided by Emily Sun and Andrew Marson-Neep of Envision Pharma Group (Philadelphia PA, USA).

Legal entity responsible for the study

Incyte Corporation, Wilmington, DE.

Funding

Incyte Corporation, Wilmington, DE.

Disclosure

D.J. Pinato: Financial Interests, Personal, Other, travel grant and advisory/speaker fees: AstraZeneca, Avammune, Bayer, Bristol Myers Squibb, Da Volterra, Eisai, Falk Pharma, H3 Biomedicine, Ipsen, Lift Biosciences, Mina Therapeutics, MSD Oncology, Mursla Bio, Roche, Roche/Genentech, Starpharma, ViiV Healthcare; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, GSK, MSD Oncology; Financial Interests, Personal, Other: Wiley. U. Banerji: Financial Interests, Personal, Other, travel grant and advisory fees: Bayer, Boehringer Ingelheim, Janssen, Pegascy, Sierra Oncology; Financial Interests, Institutional, Research Funding: AstraZeneca, BTG, Carrick Therapeutics, Chugai Pharma, Onyx, Verastem. S. Rottey: Financial Interests, Personal, Other, travel grants and advisory/speaker fees: Novartis, Roche, Pfizer, MSD, Bristol Myers Squibb, Ipsen; Financial Interests, Personal, Research Grant: Roche, MSD. K. Peltola: Financial Interests, Personal, Advisory Board: MSD, Ipsen, Roche, BMS, Pfizer, Lilly, Novartis, Bayer; Financial Interests, Personal, Stocks/Shares: Faron Pharmaceuticals; Financial Interests, Institutional, Local PI, Conduct of sponsored clinical trial: Novartis; Financial Interests, Institutional, Local PI, Sponsored clinical trial: Exelixis; Financial Interests, Institutional, Local PI, Several clinical trials: BMS, MSD, Roche; Financial Interests, Institutional, Local PI, clinical trials: Incyte; Financial Interests, Institutional, Local PI, Conduct of clinical trials: Pfizer; Financial Interests, Institutional, Local PI, Conduct of clinical trial: Bayer. R. Kristeleit: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Clovis Oncology, GSK and Incyte ; Financial Interests, Personal, Other, Travel grant: AstraZeneca, GSK and Sierra Oncology ; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Speaker, Consultant, Advisor: Basilea Pharmaceutica and Shattuck Pharma. M. Gutierrez: Financial Interests, Personal, Other, travel grand and speaker fees: BMS, Guardant Health, Lilly, Merck; Financial Interests, Personal, Stocks or ownership: Cota Healthcare; Financial Interests, Institutional, Research Funding: Acerta Pharma, Adlai Nortye, Arcus Biosciences, Array BioPharma, Bayer, Bellicum Pharmaceuticals, BMS, Boehringer Ingelheim, Celgene, Checkpoint Therapeutics, Compass Therapeutics, Constellation Pharmaceuticals, Cullinan Oncology, Cyteir, Daiichi Sankyo. S.N. Symeonides: Financial Interests, Institutional, Speaker, Consultant, Advisor: Bicycle Therapeutics, Boxer Capital, Bristol Myers Squibb, Duke Street Bio, Eisai, Ellipses Pharma, Eugit Therapeutics, EUSA Pharma, Exscientia, Ipsen, MedAnnex, MSD, Pfizer/EMD Serono, Vaccitech; Financial Interests, Personal, Other, Travel Grant: BioNTech, Bristol Myers Squibb, EUSA Pharma, Ipsen, MSD; Financial Interests, Institutional, Research Funding: MSD and Verastem. M. Hoejgaard: Financial Interests, Institutional, Research Funding: Puma Biotechnology, Roche/Genentech, AstraZeneca, Incyte, Pfizer, Orion Pharma, MSD, Merck, Bristol Myers Squibb, Novartis, Lilly Pharmaceuticals/ Loxo Oncology, Bayer/Loxo Oncology, Amgen, Repare Therapeutics, Genmab, Kinnate Biopharma; Financial Interests, Personal, Stocks/Shares: Bavarian Nordic, Agilent, Illumina, Pacific Biosciences; Financial Interests, Personal, Other, Board Member: Danish Medicines Council. V. Ebiana, J. Daniel, J. Pulini: Financial Interests, Personal, Full or part-time Employment: Incyte Corporation; Financial Interests, Personal, Stocks or ownership: Incyte Corporation. All other authors have declared no conflicts of interest.