159TiP - Two Phase 1 Studies Assessing the Safety and Efficacy of the Small Molecule Oral PD-L1 Inhibitor INCB099280 in Combination with Adagrasib (INCB 99280-204 [Study 204]) or Ipilimumab (INCB 99280-205 [Study 205]) in Adults with Advanced Solid Tumors

Background

INCB099280, an oral programmed death ligand 1 (PD-L1) inhibitor, has shown acceptable safety and preliminary efficacy in advanced solid tumors in an ongoing phase 1 study (Prenen et al. SITC 2022). As combination treatment (tx) can enhance the antitumor activity of anti-PD-1 therapy, we plan to conduct 2 Phase 1, open label, multicenter studies to evaluate safety and efficacy of INCB099280 combination tx in adults with select solid tumors. Study 204 will evaluate INCB099280 with adagrasib, an inhibitor of KRAS^G12C, a common mutation in non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Study 205 will evaluate INCB099280 with ipilimumab (IPI), a CTLA4 inhibitor that has shown synergistic antitumor activity with anti PD-1 agents in clinical studies.

Trial Design

Eligibility criteria and dosing are outlined in Table. Both studies will consist of Part 1 dose-escalation and Part 2 dose-expansion. Part 1 will follow a hybrid of modified toxicity probability interval type design and dose-toxicity model. In Part 2, for Study 204, patients (pts) in NSCLC and CRC tumor-specific cohorts will be randomized within each cohort to ≤3 selected recommended doses for expansion (RDEs); for Study 205, pts in renal cell (RCC) and hepatocellular carcinoma (HCC) cohorts will be randomized 1:1 within each cohort to 1 of 2 selected RDEs. Pts will be treated with INCB099280 for ≤2 years, followed by a 90-day safety follow-up period . Primary endpoints are dose-limiting toxicities, tx emergent adverse events (TEAEs), and TEAEs leading to dosing modifications. Secondary/exploratory endpoints will include INCB099280 pharmacokinetic parameters, objective response, disease control, and duration of response. Recruitment has started for both studies. Table: 159TiP

Eligibility criteria and dosing

Clinical trial identification

NCT06039384, NCT05909995.

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. Berz: Financial Interests, Personal, Advisory Board: Biocept, Prelude Dx; Financial Interests, Personal, Speaker’s Bureau: Caris Life Sciences, Tempus, Natera, Biocept, Boehringer Ingelheim, Genentech, Novartis, AstraZeneca, Sun, and Oncocyte. D.J. Pinato: Financial Interests, Personal, Speaker, Consultant, Advisor: ViiV Healthcare, Bayer Healthcare, Roche, Mursla, MiNa Therapeutics, Eisai, H3B, AstraZeneca, DaVolterra, Exact Sciences, Ipsen, Avamune, and Lift Biosciences; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, GSK, and MSD. M. Barve: Financial Interests, Personal, Full or part-time Employment: Texas Oncology; Financial Interests, Personal, Stocks or ownership: Texas Oncology; Financial Interests, Personal, Research Funding: Mary Crowley Research Center. J. Pulini, J. Bowman: Financial Interests, Personal, Full or part-time Employment: Incyte Corporation; Financial Interests, Personal, Stocks or ownership: Incyte Corporation. M.L. Johnson: Financial Interests, Personal, Speaker, Consultant, Advisor: Genentech/Roche, AstraZeneca, Calithera Biosciences, Merck, Sanofi, Mirati Therapeutics, Ribon Therapeutics, AbbVie, GSK, Gritstone Bio, Janssen Oncology, Lilly, Amgen, Daiichi Sankyo, Eisai, Axelia Oncology, Black Diamond Therapeutics, CytomX; Financial Interests, Institutional, Research Funding: EMD Serono, Kadmon, Janssen, Mirati Therapeutics, Genmab, Pfizer, AstraZeneca, Stem CentRx, Novartis, Array BioPharma, Regeneron, Merck, Hengrui Pharmaceutical, Lycera, BeiGene, Tarveda Therapeutics, Loxo, AbbVie, Boehringer Ingelheim, Guardant Health, Da; Financial Interests, Personal, Other, Travel grant: AbbVie, AstraZeneca, Genentech, Incyte, Merck, Pfizer, Sanofi.