155P - A Phase 1 Study Exploring the Safety and Tolerability of the Small-Molecule PD-L1 Inhibitor INCB099280 in Select Advanced Solid Tumors

Background

INCB099280, 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 (pts) with advanced solid tumors (Prenen, et al. SITC 2022). Here we present updated results.

Methods

Eligible pts were ≥18 years with ECOG PS ≤1, and disease progression after available treatment (tx) or were ineligible for/without access to standard tx. In part 1, INCB099280 dose was escalated from 100 mg QD with a Bayesian optimal interval design. In part 2, 3 expansion cohorts with select tumor types were studied: 1) IO-naive pts, 2) IO-naive pts with MSI-H/dMMR tumors, 3) pts who progressed on anti-PD-1 mAb. Primary endpoints are INCB099280 safety, tolerability, and pharmacologically active/MTD determination. INCB099280 pharmacokinetics, objective response rate per RECIST v1.1, and biomarkers of pharmacologic activity were also analyzed.

Results

As of June 22, 2023, 172 pts had received INCB099280 at doses from 100 mg QD to 800 mg BID (median age, 63 years [range, 21–86]; ≥2 prior lines of tx, 64.0%; prior IO, 14.5%; most common tumor types: anal [14.5%], cervical [8.7%], and colorectal [7.6%]). Dose was escalated to 800 mg BID; MTD was not reached. 5 dose levels were expanded in part 2 up to 800 mg BID. Overall, 137 pts (79.7%) discontinued treatment, 119 (69.2%) due to disease progression; 95.3% of pts had ≥1 tx-emergent adverse event (TEAE) (Table). Several responses have been observed, and updated results will be presented. In pts with complete response (n=2), baseline tumor mutational burden scores were high (34–49 mut/Mb) and ctDNA levels at cycle 4 day 1/end of tx had decreased by 92.3% from baseline. Table: 155P

Safety

Conclusions

INCB099280 was generally well tolerated at all doses tested. Updated results indicate promising antitumor activity and support future development of INCB099280 as monotherapy and in combination regimens for advanced solid tumors.

Clinical trial identification

NCT04242199.

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

H. Prenen: Financial Interests, Personal, Speaker, Consultant, Advisor: Biocartis, Cureteq; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bayer, Roche, and Sanofi. T. Lesimple: Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, MSD, Novartis, and Pierre Fabre. M. Robert: Financial Interests, Personal, Advisory Board: AstraZeneca and Eisai; Financial Interests, Personal, Other, Travel Grants: AstraZeneca. B.R. Delafontaine: Financial Interests, Personal, Speaker, Consultant, Advisor: Sanofi. P. Tomasini: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, AstraZeneca, Bristol Myers SquibbFoundation, Janssen, Roche, and Takeda; Financial Interests, Institutional, Funding: AstraZeneca, Bristol Myers Squibb/Pfizer and Takeda. T. Meniawy: Financial Interests, Personal, Speaker, Consultant, Advisor: BMS GmbH & Co. KG, Eisai, GSK, MSD, Novartis, Regeneron, and Sanofi; Financial Interests, Institutional, Research Funding: AstraZeneca/MedImmune, Bayer, BeiGene, Bristol Myers Squibb, Incyte, Merck Serono, Regeneron, Roche/Genentech. E. Van Cutsem: Financial Interests, Personal, Speaker, Consultant, Advisor: Array, AstraZeneca, Bayer, Biocartis, Bristol Myers Squibb, Celgene, Eli Lilly, Ipsen, MSD, Merck KGaA, Novartis, Pierre Fabre, Roche, Servier, Sirtex, and Taiho; Financial Interests, Institutional, Research Funding: Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Ipsen, Merck, Merck KGaA, Novartis, Roche, and Servier. S.A. Piha-Paul: Financial Interests, Institutional, Research Funding: AbbVie, Inc., ABM Therapeutics, Inc., Acepodia, Inc, Alkermes, Aminex Therapeutics, Amphivena Therapeutics, Inc., BioMarin Pharmaceutical, Inc, Boehringer Ingelheim, Bristol Myers Squibb, Cerulean Pharma, Inc., Chugai Pharmaceutical Co., Ltd, Curis, Inc.; Financial Interests, Personal, Speaker, Consultant, Advisor: CRC Oncology. M.T. Schweizer: Financial Interests, Personal, Other, Consultancy/Honoraria: AstraZeneca, PharmaIn, Resverlogix, and Sanofi; Financial Interests, Institutional, Research Funding: Ambrix, Inc., AstraZeneca, Bristol Myers Squibb, Hoffman-La Roche, Immunomedics, Janssen, Madison Vaccines, Merck, Pfizer, SignalOne Bio, Tmunity, and Zenith Epigenetics. S. Gadgeel: Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Daichii Sanyko , Eisai, Genentech/Roche, Gilead Sciences, GSK, Janssen Oncology, Lilly; Merck, Mirati Therapeutics, Novartis, Pfizer, Takeda; Financial Interests, Institutional, Research Funding: Amgen (Inst), Astellas Pharma (Inst), AstraZeneca, AstraZeneca (Inst), BioMed Valley Discoveries (Inst), Blueprint Medicines (Inst), Calithera Biosciences (Inst), Daichii Sankyo (Inst), Daiichi Sankyo (Inst), Dragonfly Therapeutics (Inst), eFFECTOR Therap; Financial Interests, Personal, Other, travel, accommodations, expenses: Mirati Therapeutics; Financial Interests, Personal, Other: AstraZeneca. S. Kondo: Financial Interests, Personal, Speaker’s Bureau: Incyte; Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Eisai, and Incyte; Financial Interests, Personal, Speaker, Consultant, Advisor: Takeda; Financial Interests, Institutional, Research Funding: AbbVie (Inst), AstraZeneca (Inst), Eisai (Inst), and Lilly (Inst). K. Ouali: Financial Interests, Personal, Speaker, Consultant, Advisor: Sotio; Financial Interests, Institutional, Funding: Amgen and Sotio. Y. Kuboki: Financial Interests, Institutional, Research Funding: Taiho, Takeda, AstraZeneca, Daiichi Sankyo, Boehringer Ingelheim, Amgen, Chugai, Genmab, GSK, and Incyte; Financial Interests, Personal, Funding: Taiho, Ono, Bayer, Lilly, Bristol Myers Squibb, and Merck Serono; Financial Interests, Personal, Advisory Role: Taiho, Takeda, and Amgen. J. Daniel, V. Ebiana, J. Howe, S. Spitz: Financial Interests, Personal, Full or part-time Employment: Incyte Corporation; Financial Interests, Personal, Stocks or ownership: Incyte Corporation. A. Italiano: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, BMS, MSD, Parthenon, and Roche; Financial Interests, Institutional, Research Funding: AstraZeneca, Bayer, BMS, MSD, PharmaMar, and Roche. All other authors have declared no conflicts of interest.