A PHASE 2 STUDY EVALUATING INCB099280 IN PARTICIPANTS WITH SELECT SOLID TUMORS WHO ARE IMMUNE CHECKPOINT INHIBITOR–NAÏVE

Trial ID: 2022-502716-37-00
Protocol: INCB 99280-211
Sponsor: Incyte Corp.

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Diseases & Conditions

Hepatocellular carcinoma Bladder transitional cell carcinoma stage IV Transitional cell carcinoma Non-small cell lung cancer

Objectives

The primary objective of this Phase 2 study is to evaluate the **safety**, tolerability, and preliminary efficacy of INCB099280 administered at doses of 400 mg BID, 600 mg BID, and 800 mg BID in participants with advanced solid tumors. This is clinically relevant as it aims to establish the therapeutic potential and safety profile of INCB099280 in a population that is naive to immune checkpoint inhibitors, which could provide a new treatment option for these patients.

Secondary objectives include:

Determining the efficacy of INCB099280 at the specified doses with respect to disease control and response duration in participants with advanced solid tumors.
Characterizing the pharmacokinetics (PK) of INCB099280 in plasma in these participants.

Participants

The clinical trial involves a total of **258 participants** diagnosed with **recurrent or advanced/metastatic solid tumors** who are immunotherapy naive. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on their ability to comprehend and sign an informed consent form, and they must have a measurable disease as per RECIST v1.1 criteria. The trial includes individuals with an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1, although a score of up to 2 is permitted for those with urothelial carcinoma (UC). Participants are required to have a life expectancy of more than three months and must agree to avoid pregnancy or fathering children during the study. The trial population is not restricted by specific lifestyle considerations such as diet or physical activity, but it does include a vulnerable population. The selection criteria ensure that participants have prior systemic therapy experience, although they must be naive to immunotherapy.

Plans and Procedures

The clinical trial is designed to evaluate the **safety**, tolerability, and preliminary efficacy of the investigational drug INCB099280 in participants with recurrent or advanced/metastatic solid tumors who are immunotherapy-naive. This is a Phase II, randomized, double-blind, controlled study. The trial will assess three different dosages of INCB099280: 400 mg, 600 mg, and 800 mg, administered orally twice daily. The study is expected to run until June 2024, with recruitment having commenced in August 2023. Participants will be involved in the study for a maximum treatment period of 24 weeks, unless early termination criteria are met.

The sequence of study visits includes an initial **screening** visit to determine eligibility based on inclusion criteria such as age, prior therapy, and performance status. Participants must have a measurable disease per RECIST v1.1 and a life expectancy greater than three months. Following the screening, eligible participants will undergo regular follow-up visits to monitor the incidence of treatment-emergent adverse events (TEAEs), assess vital signs, and conduct laboratory tests. The primary endpoints include objective response rates and the incidence of TEAEs, while secondary endpoints focus on disease control, duration of response, time to response, progression-free survival, overall survival, and plasma concentration of INCB099280.

The end-of-study visit will occur after the completion of the treatment period or upon early termination. Conditions that may lead to early termination include significant adverse events, disease progression, or withdrawal of consent. Participants are required to avoid pregnancy or fathering children during the study. The trial aims to provide valuable insights into the potential benefits and risks of INCB099280 for patients with specific solid tumors, contributing to the advancement of cancer treatment options.

Treatment

The clinical trial involves the administration of **INCB099280**, an experimental medication developed by Incyte Corporation. **INCB099280** is formulated as a **film-coated tablet** and is intended for **oral use**. The active substance, also named **INCB099280**, is of chemical origin. The trial evaluates three dosing regimens: 400 mg, 600 mg, and 800 mg, each administered twice daily (BID). The maximum daily dose is set at 1600 mg, with a total treatment period not exceeding 24 weeks. The study aims to assess the safety, tolerability, and preliminary efficacy of **INCB099280** in participants with advanced solid tumors who are immune checkpoint inhibitor-naïve.

In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments, as deemed necessary by the study protocol. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial does not involve any pediatric formulations, and **INCB099280** is not classified as an orphan drug. The pharmaceutical form and administration route are consistent with standard practices for oral medications in oncology trials.

Efficacy

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints include the **objective response**, defined as having a best overall response of confirmed complete response (CR) or partial response (PR) by investigator assessment per RECIST v1.1, and the incidence of treatment-emergent adverse events (TEAEs), which will be evaluated through physical examinations, changes in vital signs and ECGs, and analysis of clinical laboratory samples. Additionally, the incidence of TEAEs leading to dose interruption, dose reduction, or study drug discontinuation will be monitored.

Secondary endpoints will further evaluate efficacy through measures such as disease control, defined as having a best overall response of confirmed CR, PR, or stable disease (SD) after a minimum of 15 weeks following the initiation of study treatment by investigator assessment per RECIST v1.1. Other secondary endpoints include duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and the concentration of INCB099280 in plasma. These parameters will be assessed at various timepoints throughout the study, with specific criteria for each endpoint as outlined in the protocol.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Ability to comprehend and willingness to sign a written ICF for the study.
Age 18 years or older inclusive at the time of signing the ICF.
Prior systemic therapy, diagnoses, and disease settings as follows: a. Immunotherapy naive b. Measurable disease per RECIST v1.1 c. One of the following disease settings: see protocol
ECOG performance score of 0 or 1 (except for UC, where a score of up to 2 is permitted).
Life expectancy > 3 months
Willingness to avoid pregnancy or fathering children

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Exclusion Criteria

Known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of disease recurrence for 3 years since initiation of that therapy.
CNS metastases requiring treatment and/or leptomeningeal disease.
Toxicity from prior therapy that has not recovered to ≤ Grade 1 or baseline
Prior receipt of an anti–PD-1, anti–PD-L1, or anti–PD-L2 agent or treatment with an immune modulator
Received thoracic radiation of > 30 Gy within 6 months of the first dose of study treatment.
Participation in another interventional clinical study while receiving INCB099280.
Treatment with anticancer medications or investigational drugs within the detailed intervals before the first administration of study drug
Impaired cardiac function or clinically significant cardiac disease
History or evidence of interstitial lung disease including noninfectious pneumonitis.
Presence of gastrointestinal conditions that may affect drug absorption, as well as those that interfere with gastrointestinal transit
Any autoimmune disease requiring systemic treatment in the past 5 years, including corticosteroids of a daily dose exceeding 10 mg of prednisone or equivalent
Diagnosis of primary immunodeficiency or receiving chronic systemic steroid therapy at a daily dose exceeding 10 mg of prednisone or equivalent
HIV infection and any one or more of the following: CD4+ T-cell count < 200 cells/µL, detectable viral load per parameters of assay, or antiretroviral therapy regimen containing moderate or potent CYP3A4/CYP3A5 inhibitors or inducers
Active infection requiring systemic therapy, with the exception of HIV and hepatitis
History of organ transplantation, including allogeneic stem cell transplantation.
Known hypersensitivity or severe reaction to any component of study drug or formulation components.
Postoperative complications preventing the participant from adhering protocol assessments and procedures.
Receipt of systemic antibiotics within 28 days of first dose of study treatment.
Probiotic usage is prohibited during screening and throughout the study treatment period.
Received a live vaccine within 28 days of the planned start of study drug. Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, some shingles, yellow fever, rabies, BCG, and typhoid vaccines. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live-attenuated vaccines and are not allowed. Note: If enrolled, participants should not receive live vaccine during the study and up to 28 days after the last dose of study drug.
Treatment with moderate and potent CYP3A4/CYP3A5 inhibitors or inducers
Unable to be weaned off of a prohibited medication before the initiation of study treatment.
Participants with laboratory values at screening as defined in the protocol
Clinically significant ECG abnormality, including average QTcF interval > 480 milliseconds
Active HBV or HCV as follows (testing must be performed): a.Detectable HBV DNA (viral load) and HBsAg. b. Participants with chronic HBV infection with active disease who meet the criteria for anti-HBV therapy are required to be on a suppressive antiviral therapy prior to initiation of study treatment. c. Active HCV is defined as a positive HCV antibody result and quantitative HCV RNA (viral load) result greater than the lower limit of detection
Pregnant, expecting to conceive, or breastfeeding or expecting to father children
Any condition that would, in the investigator's judgment, interfere with full participation in the study
The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection, or who are unable to express their consent per article L.1121-8 of the French Public Health Code, not affiliated to a social security per article L.1121-8-1 of the French Public Health Code.