Interventional Study of INCB 99280 With Ipilimumab in Participants With Select Solid Tumors

A Phase 1 Study of INCB099280 in Combination With Ipilimumab in Participants With Select Solid Tumors

The purpose of this study is to characterize the safety, tolerability, PK, and efficacy of INCB 99280 in combination with ipilimumab in participants with select solid tumors.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Hepatocellular Carcinoma (HCC); Renal Cell Carcinoma (RCC); Colorectal Carcinoma (CRC); Microsatellite Instability - High (MSI-H); Mismatch Repair Deficient (dMMR)
• Intervention / Treatment: Drug: INCB 99280 with Ipilimumab

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Center
• South Africa
  • Centurion, South Africa, 01692
    • Johese Clinical Research: Midstream
  • Pretoria, South Africa, 00181
    • Mary Potter Oncology Centre
• United States
  • California
    • Los Angeles, California, United States, 90067
      • Valkyrie Clinical Trials
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Prior systemic therapy, diagnoses and disease setting as follows:

  • For Part 1 (dose escalation), and no history of treatment with anti-CTLA-4 or anti-PD-(L)1 therapy and one of the following,

    • Unresectable or metastatic cutaneous melanoma, or
    • Unresectable of metastatic Child-Pugh Class A NDD not eligible for surgical and/or locoregional therapy, or
    • Intermediate or poor-risk advanced clear cell RCC, or
    • MSI-H or dMMR metastatic CRC and able to provide fresh or archival tumor tissue for central confirmation of MSI-H or dMMR.

  • For Part 2 (dose expansion), IO treatment -naïve, e.g., no prior receipt of an anti PD-1, anti-PD-L1 or PD-L1, anti-CTLA-4, GITR, LAG3, TIM3, OX-40, IL-2, 4-1BB or other immune modulator, and have not received prior systemic therapy and one of the following,

    • Unresectable or metastatic Child-Pugh Class A HCC not eligible for surgical and/or locoregional therapy, or
    • Intermediate - or poor-risk advanced clear cell RCC.
  • ECOG performance score of 0 or 1.
  • Life expectancy > 3 months, in the opinion of the investigator.

  • Histologically confirmed solid tumors with measurable disease per RECIST v1.1.

    • Exception: HCC may be diagnoses based on cross-sectional multiphasic imagining using the AASLD criteria.
  • Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

• Known history of an additional malignancy.
• Central nervous system (CNS) metastases requiring treatment and/or leptomeningeal disease.
• Toxicity from prior therapy that has not recovered.
• Received thoracic radiation within 6 months of the first dose of study treatment.
• Participation in another interventional clinical study while receiving INCB099280.
• Impaired cardiac function of clinically significant cardiac disease.
• History of evidence of interstitial lung disease including non-infections pneumonitis.
• Presence of gastrointestinal condition that may affect drug absorption
• Any autoimmune disease requiring systemic treatment in the past 5 years.
• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy at a daily dose exceeding 10 mg of prednisone or equivalent
• Active infection requiring systemic therapy.
• History of organ transplantation, including allogeneic stem cell transplantation.
• Receipt of system antibiotics within 28 days of first dose of study treatment.
• Probiotic usage is prohibited during the screening and throughout the study treatment period.
• Received a live vaccine within 28 days of planned start of study drug.
• Laboratory values outside the Protocol-defined ranges.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Participants with RCC and MSI-H/dMMR CRC will receive 1 of two doses of INCB099280 BID with up to 4 doses of ipilimumab 1 mg/kg Q3 weeks; Participants with Melanoma and HCC will receive 1 of 2 doses of INCB099280 BID with up to 4 doses of 3 ipilimumab 3 mg/kg Q3 weeks	Drug: INCB 99280 with Ipilimumab; Dose Escalation and expansion of INCB 99280 with Ipilimumab
Experimental: Dose Expansion; Participants with RCC will receive 1 of two doses of INCB099280 BID with up to 4 doses of ipilimumab 1 mg/kg Q3 weeks of ipilimumab; Participants with HCC will receive 1 of two doses of INCB099280 BID with up to 4 doses of ipilimumab 3 mg/kg Q3 weeks of ipilimumab	Drug: INCB 99280 with Ipilimumab; Dose Escalation and expansion of INCB 99280 with Ipilimumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurence of DLTs		2 Years
Incidence of TEAEs	Assessed by physical examinations, changes in vital signs and ECGs, and analysis of clinical laboratory samples.	2 Years
Incidence of TEAEs leading to dose interruption, dose reduction, or discontinuation of either of the study drugs		2 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of INCB099280 in plasma		2 Years
Objective response	Defined as having a best overall response of complete response or partial response by investigator assessment per RECIST v1.1.	2 Years
Disease control	Defined as having a best overall response of complete response or partial response, or stable disease of ≥ 15 weeks after initiation of study treatment, by investigator assessment per RECIST v1.1.	2 Years
Duration of Response	Defined as the time from the earliest date of CR or PR until the earliest date of disease progression (by investigator assessment per RECIST v1.1) or death due to any cause if occurring sooner than progression.	2 Years

Collaborators and Investigators

• Sponsor: Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2023
• Primary Completion (Actual): September 19, 2024
• Study Completion (Actual): November 11, 2024

Study Registration Dates

• First Submitted: June 9, 2023
• First Submitted That Met QC Criteria: June 9, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Colonic Diseases; Urologic Neoplasms; Kidney Neoplasms; Genomic Instability; Carcinoma; Colorectal Neoplasms; Carcinoma, Renal Cell; Microsatellite Instability; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Ipilimumab
• Other Study ID Numbers: INCB 99280-205; 2023-503243-34-00 (Registry Identifier: EU CT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No