Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099318 in Participants With Advanced Solid Tumors

NCT04272034 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: INCB 99318-1222019-004990-21
• Study Type: interventional
• Target: 105
• Locations: 7 countries
• Sites: 24

Brief Summary

The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of INCB099318 in select solid tumors.

Conditions

Advanced Solid Tumors; MSI-H/dMMR Tumors; Cutaneous Squamous Cell Carcinoma; Urothelial Carcinoma, HCC; Cervical Cancer; Esophageal Squamous Cell Carcinoma; Merkel Cell Carcinoma; Small-cell Lung Cancer; Mesothelioma; PD-L1 Amplified Tumor (9p24.1); Nasopharyngeal Carcinoma; Cyclin-dependent Kinase 12 Mutated Tumors; Basal Cell Carcinoma (Unresectable or Metastatic); Sarcomatoid Renal Cell Carcinoma; Clear Cell Ovarian or Endometrial Carcinoma; Anal Carcinoma; Squamous Cell Penile Carcinoma; DNA Polymerase Epsilon Mutated Tumors (P286R and V411L)

Keywords

Advanced solid tumors

Outcome Measures

Primary Outcomes (1)

• Number of treatment-emergent adverse events

  Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 30 days after last dose of study drug.

  Up to approximately 25 months

Secondary Outcomes (8)

• Cmax of INCB099318

  Up to approximately 3 months

• tmax of INCB099318

  Up to approximately 3 months

• Cmin of INCB099318

  Up to approximately 3 months

• AUC0-t of INCB099318

  Up to approximately 3 months

• t½ of INCB099318

  Up to approximately 3 months

Study Arms (3)

Cohort 1

EXPERIMENTAL

Participants with select solid tumors who are immunotherapy treatment-naive

Drug: INCB099318

Cohort 2

EXPERIMENTAL

Participants with high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR) tumors who are immunotherapy treatment-naïve.

Drug: INCB099318

Cohort 3

EXPERIMENTAL

Participants with progression of any solid tumor treated with an approved anti-PD-1 monoclonal antibody therapy

Drug: INCB099318

Interventions

INCB099318 DRUG

INCB099318 administered orally in 20 mg or 100 mg tablets once daily or twice daily on each day of each 28-day cycle.

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have disease progression after treatment with available therapies that are known to confer clinical benefit or must be intolerant to or ineligible for standard treatment.
• Histologically confirmed advanced solid tumors (protocol-defined select solid tumors) with measurable lesions per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) that are considered nonamenable to surgery or other curative treatments or procedures.
• ECOG performance status score of 0 or 1.
• Life expectancy \> 12 weeks.
• Willingness to avoid pregnancy or fathering children.

You may not qualify if:

• Laboratory values outside the Protocol-defined ranges.
• Clinically significant cardiac disease.
• History or presence of an ECG that, in the investigator's opinion, is clinically meaningful.
• Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain or CNS metastases).
• Known additional malignancy that is progressing or requires active treatment.
• Has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy (including prior IO) and/or complications from prior surgical intervention before starting study treatment.
• Prior receipt of an anti-PD-L1 therapy.
• Treatment with anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.
• A 28-day washout for systemic antibiotics is required.
• Probiotic usage while on study and during screening is prohibited.
• Active infection requiring systemic therapy.
• Known history of HIV
• Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (24)

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Prisma Health Cancer Institute Faris

Greenville, South Carolina, 29605, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Universitair Ziekenhuis Brussel

Brussels, 01090, Belgium

Location

Institut Jules Bordet

Brussels, B-1070, Belgium

Location

Universitair Ziekenhuis Antwerpen (Uza)

Edegem, 02650, Belgium

Location

Ghent University Hospital

Ghent, 09000, Belgium

Location

Universitaire Ziekenhuis Leuven - Gasthuisberg

Leuven, 03000, Belgium

Location

Rigshospitalet Uni of Hospital of Copenhagen

Copenhagen, 02100, Denmark

Location

Helsinki University Central Hospital

Helsinki, 00029, Finland

Location

Docrates Cancer Center

Helsinki, 00180, Finland

Location

Tampere University Hospital

Tampere, 33520, Finland

Location

Turku University Hospital

Turku, 20520, Finland

Location

Haukeland University Hospital

Bergen, 05051, Norway

Location

Oslo University Hospital

Oslo, 00450, Norway

Location

Sahlgrenska University Hospital

Gothenburg, 41345, Sweden

Location

Karolinska University Hospital Solna

Solna, 17164, Sweden

Location

Uppsala Universitet - Akademiska Sjukhuset

Uppsala, 75185, Sweden

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

St James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Guys and St Thomas Nhs Foundation Trust

London, SE1 9RT, United Kingdom

Location

The Royal Marsden Hospital Nhs Trust London

London, SM2 5PT, United Kingdom

Location

Imperial College Healthcare Nhs Trust - Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Freeman Hospital Newcastle Upon Tyne Foundation Nhs Trust

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Uterine Cervical Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma, Merkel Cell; Small Cell Lung Carcinoma; Mesothelioma; Nasopharyngeal Carcinoma; Carcinoma, Basal Cell; Neoplasm Metastasis; Carcinoma, Renal Cell; Endometrial Neoplasms; Anus Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Carcinoma, Squamous Cell; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Adenocarcinoma; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenoma; Neoplasms, Mesothelial; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms, Basal Cell; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Intestinal Diseases; Anus Diseases; Rectal Diseases

Study Officials

• Louis Viviers, MD

  Incyte Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of 2 parts. Part 1 is a dose-escalation design to identify the maximum tolerated dose and/or pharmacologically active dose for INCB099318. Part 2 is an expansion at 1 or more dose levels to further explore safety, preliminary efficacy, pharmacoketics, and pharmacodynamic effects.

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: February 17, 2020
• Study Start: March 26, 2021
• Primary Completion: August 16, 2024
• Study Completion: August 16, 2024
• Last Updated: October 16, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

FI (4); SE (3); DK (1); NO (2); GB (6); US (3); BE (5)