Clinical trial NCT05879822: A Study to Evaluate INCB099280 in Participants With Select Solid Tumors Who Are Immune Checkpoint Inhibitor Naive
Official title: A Phase 2 Study Evaluating INCB099280 in Participants With Select Solid Tumors Who Are Immune Checkpoint Inhibitor Naive
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Advanced Solid Tumor
Keywords: Advanced Solid Tumor
Hepatocellular Carcinoma
Cutaneous Melanoma
PD-L1-positive NSCLC
Non-small Cell Lung Cancer
Renal Cell Carcinoma
Urothelial Cancer
MSI-H/dMMR Tumors
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2023-05-30
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study consists of 2 parts. In Part 1, participants with 6 different tumor types will be randomized 1:1:1 to INCB099280 Dose 1, INCB099280 Dose 2, or INCB099280 Dose 3 twice daily (BID). At the end of Part 1, an integrated analysis will be performed to select a dose. Once a dose is selected, Part 2 will proceed to complete enrollment for each of the 6 disease-specific cohorts at the selected dose.
Primary purpose: TREATMENT

Brief summary: This study is being conducted to determine the safety, tolerability, and preliminary efficacy of INCB099280 in participants with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

* Immunotherapy naive and without access to approved and/or available immune checkpoint inhibitor (ICI) therapy.
* Measurable disease per RECIST v1.1.
* One of the following disease settings:

  * Unresectable or metastatic Child-Pugh Class A hepatocellular carcinoma (HCC) not eligible for surgical and/or locoregional therapy and have not received prior systemic therapy or had disease progression following primary therapy.
  * Unresectable or metastatic cutaneous melanoma and have not received more than 1 previous systemic therapy for advanced disease.
  * Unresectable Stage III PD-L1-positive (TPS ≥ 50% using the Dako PD-L1 IHC 22C3 assay) non-small cell lung cancer (NSCLC) without actionable molecular biomarkers and have not received prior systemic therapy and where chemoradiation is contraindicated; in addition, able to provide fresh or archival tumor tissue for central confirmation of PD-L1 expression.
  * Stage IV PD-L1-positive (TPS ≥ 50% using the Dako PD-L1 IHC 22C3 assay) NSCLC without actionable molecular biomarkers and have not received prior systemic therapy; in addition, able to provide fresh or archival tumor tissue for central confirmation of PD-L1 expression.
  * Relapsed or Stage IV clear cell renal cell carcinoma (RCC) after having received 1 prior systemic therapy for relapsed or Stage IV disease.
  * Cisplatin-ineligible, locally advanced or Stage IV urothelial cancer (UC) and have not received prior systemic therapy for locally advanced or Stage IV UC and able to provide fresh or archival tumor tissue for central confirmation of PD-L1 expression using the Dako PD-L1 IHC 22C3 assay.
  * Advanced or metastatic microsatellite instability high (MSI-H) or deficient mismatch repair (dMMR) (as determined by an approved assay) solid tumors and able to provide fresh or archival tumor tissue for central confirmation of MSI-H or dMMR.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
* Life expectancy \> 3 months.
* 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.
* Prior receipt of an PD-1, anti-PD-L1, or anti-PD-L2 agent or treatment with an immune modulator (eg, CTLA-4, GITR, LAG3, TIM3, OX40, ICOS, IL-2, 4-1BB, CAR-T cell).
* 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 or clinically significant cardiac disease.
* History or evidence of interstitial lung disease including noninfectious pneumonitis.
* Presence of gastrointestinal conditions 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 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.
* Laboratory values outside the Protocol-defined ranges.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 2 years
measure: Number of participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 2 years 3 months
measure: Number of participants with TEAEs leading to dose modification or discontinuation
timeFrame: Up to 2 years
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: Up to 2 years
measure: Duration Of Response (DOR)
timeFrame: Up to 2 years
measure: INCB099280 pharmacokinetic (PK) in Plasma
timeFrame: Pre dose and 1, 2 and 6 hours post dose on Cycle 1 Day 1 and Cycle 2 Day 1. Pre dose every other cycle until Cycle 11 Day 1 (Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1 and Cycle 11 Day 1) (each cycle is 28 days)
Other outcomes:
Locations:
city: Barretos
country: Brazil
facility: Fundacao Pio Xii Hospital de Cancer de Barretos
city: Curitiba
country: Brazil
facility: Cionc-Centro Integrado de Oncologia de Curitiba
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner - Liga Paranaense de Combate Ao Câncer
city: Ijui
country: Brazil
facility: Oncosite - Centro de Pesquisa Clinica E Oncologia
city: Itajaí
country: Brazil
facility: Clinica de Neoplasias Litoral Ltda
city: JAÚ
country: Brazil
facility: Fundacao Doutor Amaral Carvalho
city: Londrina
country: Brazil
facility: Hospital de Cancer de Londrina
city: Porto Alegre
country: Brazil
facility: Irmandade Da Santa Casa de Misericordia de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Hgb - Hospital Giovanni Battista - Mae de Deus Center
city: Porto Alegre
country: Brazil
facility: Hospital Ernesto Dornelles
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora Da Conceicao
city: Santo Andre
country: Brazil
facility: Cepho - Centro de Estudos E Pesquisas de Hematologia E Oncologia
city: São Paulo
country: Brazil
facility: A. C. Camargo Cancer Center
city: Nanning
country: China
facility: The People'S Hospital of Guangxi Zhuang Autonomous Region
city: Batumi
country: Georgia
facility: High Technology Hospital Medcenter
city: Kutaisi
country: Georgia
facility: Jsc Evex Hospitals
city: Tbilisi
country: Georgia
facility: Caucasus Medical Centre Llc
city: Tbilisi
country: Georgia
facility: Archangel St. Michael Multi Profile Clinical Hospital
city: Tbilisi
country: Georgia
facility: Israel-Georgian Medical Research Clinic Helsicore
city: Tbilisi
country: Georgia
facility: Todua Clinic, Llc
city: Tbilisi
country: Georgia
facility: New Hospitals
city: Tbilisi
country: Georgia
facility: Tim-Tbilisi Institute of Medicine Ltd
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic, Llc
city: Tbilisi
country: Georgia
facility: Institute of Clinical Oncology Ltd
city: Tbilisi
country: Georgia
facility: Cancer Research Center Ltd
city: Tbilisi
country: Georgia
facility: Medulla Chemotherapy and Immunotherapy Clinic
city: Athens
country: Greece
facility: 251 Air Force General Hospital
city: Athens
country: Greece
facility: University Hospital of West Attica - Attikon
city: Thessaloniki
country: Greece
facility: Euromedica General Clinic of Thessaloniki
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Rotorua
country: New Zealand
facility: Rotorua Hospital
city: Bucuresti
country: Romania
facility: Centrul Medical Medicover Victoria
city: Bucuresti
country: Romania
facility: Institutul Clinic Fundeni Clinica
city: Cluj Napoca
country: Romania
facility: Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj-Napoca
city: Cluj-napoca
country: Romania
facility: Spitalul Clinic Militar de Urgenta Dr. Constantin Papilian Cluj-Napoca
city: Cluj-napoca
country: Romania
facility: Medisprof
city: Craiova
country: Romania
facility: Centrul de Oncologie Sf. Nectarie Craiova
city: Floresti
country: Romania
facility: Sc Radiotherapy Center Cluj Srl
city: Iasi
country: Romania
facility: Institutul Regional de Oncologie Iasi
city: Ploiesti
country: Romania
facility: S.C. Medical Center Gral Srl
city: Timisoara
country: Romania
facility: S C Oncocenter Oncologie Medicala S R L
city: Timisoara
country: Romania
facility: Oncomed Srl
city: Cape Town
country: South Africa
facility: Cape Town Oncology Trials (Pty) Ltd
city: Centurion
country: South Africa
facility: Johese Clinical Research: Midstream
city: Johannesburg
country: South Africa
facility: Wits Clinical Research
city: Johannesburg
country: South Africa
facility: The Medical Oncology Centre of Rosebank
city: Port Elizabeth
country: South Africa
facility: Phoenix Pharma (Pty) Ltd
city: Adana
country: Turkey
facility: Medical Park Seyhan Hospital
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty
city: Istanbul
country: Turkey
facility: Goztepe Prof. Dr. Suleyman Yalcin City Hospital
city: Kocaeli
country: Turkey
facility: Kocaeli Universitesi Tip Fakultesi
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: