A Study of INCB099280 in Combination With Axitinib in Adults With Advanced Solid Tumors

A Phase 1/2 Study of INCB099280 in Combination With Axitinib in Adults With Advanced Solid Tumors

This study is being conducted to evaluate the safety and tolerability of INCB099280 in combination with axitinib and to assess the antitumor activity of INCB099280 in combination with axitinib. This study will only be open in the UK and EU.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: INCB099280; Drug: axitinib

• Study Type: Interventional
• Enrollment (Estimated): 145
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Incyte Corporation Call Center (ex-US); Phone Number: +800 00027423; Email: eumedinfo@incyte.com

Study Locations

• Belgium
  • Anderlecht, Belgium, 01070
    • Not yet recruiting
    • Institut Jules Bordet
  • Bruxelles, Belgium, 01200
    • Not yet recruiting
    • Cliniques Universitaires Ucl Saint-Luc
  • Edegem, Belgium, 02650
    • Not yet recruiting
    • Universitair Ziekenhuis Antwerpen (Uza)
  • Gent, Belgium, 09000
    • Not yet recruiting
    • Universitair Ziekenhuis Ghent
  • Leuven, Belgium, 03000
    • Not yet recruiting
    • Universitaire Ziekenhuis Leuven - Gasthuisberg
• France
  • Angers Cedex 2, France, 49055
    • Not yet recruiting
    • Institut de Cancerologie de L Ouest - Site Paul Papin
  • Bordeaux Cedex, France, 33076
    • Not yet recruiting
    • Institut Bergonié
  • Clermont Ferrand Cedex 01, France, 63011
    • Not yet recruiting
    • Centre Jean Perrin
  • Marseille Cedex 9, France, 13009
    • Not yet recruiting
    • Institut Paoli Calmettes
  • Paris Cedex 12, France, 75571
    • Not yet recruiting
    • Groupe Hospitalier Diaconesses - Hospital de La Croix Saint Simon
  • Rennes Cedex, France, 35042
    • Not yet recruiting
    • Centre Eugène Marquis
  • Saint Herblain, France, 44800
    • Not yet recruiting
    • Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
  • Strasbourg, France, 67200
    • Not yet recruiting
    • Institut de Cancerologie de Strasbourg
  • Villejuif Cedex, France, 94805
    • Not yet recruiting
    • Institut Gustave Roussy
• Hungary
  • Budapest, Hungary, 01122
    • Withdrawn
    • Orszagos Onkologiai Intezet
• Italy
  • Bologna, Italy, 40138
    • Not yet recruiting
    • Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola - Malpighi
  • Meldola, Italy, 47014
    • Not yet recruiting
    • Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori
  • Milano, Italy, 20141
    • Not yet recruiting
    • European Institute of Oncology
  • Milano, Italy, 20132
    • Not yet recruiting
    • Istituto Di Ricovero E Cura A Carattere Scientifico (Irccs) Ospedale San Raffaele
  • Rozzano, Italy, 20089
    • Not yet recruiting
    • Irccs Istituto Clinico Humanitas
  • Torino, Italy, 10128
    • Not yet recruiting
    • Ospedale Mauriziano Umberto I
• Spain
  • Barcelona, Spain, 08023
    • Not yet recruiting
    • Hospital Hm Nou Delfos
  • Barcelona, Spain, 08023
    • Not yet recruiting
    • Hospital Quironsalud Barcelona
  • Barcelona, Spain, 08035
    • Not yet recruiting
    • Hospital General Universitario Vall D Hebron
  • Barcelona, Spain, 08036
    • Not yet recruiting
    • Hospital Clinic Barcelona Main
  • Barcelona, Spain, 08006
    • Not yet recruiting
    • Clinica Mi Tres Torres
  • Madrid, Spain, 28041
    • Not yet recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Not yet recruiting
    • Fundacion Jimenez Diaz University Hospital
  • Madrid, Spain, 28050
    • Not yet recruiting
    • Centro Integral Oncologico Clara Campal
  • Madrid, Spain, 28022
    • Not yet recruiting
    • Clinical Universidad de Navarra Madrid
  • Pamplona, Spain, 31008
    • Not yet recruiting
    • Clinica Universidad de Navarra (Cun)
  • Pozuelo de Alarcón, Spain, 28223
    • Not yet recruiting
    • Hospital Universitario Quironsalud Madrid
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Not yet recruiting
    • Addenbrookes Hospital
  • Cardiff, United Kingdom, CF14 2TL
    • Not yet recruiting
    • Velindre Cancer Centre
  • Glasgow, United Kingdom, G12 0YN
    • Recruiting
    • Beatson West of Scotland Cancer Centrewester
  • Leeds, United Kingdom, LS9 7TF
    • Not yet recruiting
    • St James University Hospital
  • London, United Kingdom, EC1A 7BE
    • Not yet recruiting
    • St Bartholomew'S Hospital
  • London, United Kingdom, W12 0HS
    • Not yet recruiting
    • Hammersmith Hospital
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guys Hospital
  • London, United Kingdom, SW3 6JJ
    • Recruiting
    • The Royal Marsden
  • Manchester, United Kingdom, M20 4BX
    • Not yet recruiting
    • The Christie Nhs Foundation Trust Uk
  • Oxford, United Kingdom, OX3 9DU
    • Not yet recruiting
    • Oxford University Hospitals Nhs Foundation Trust
  • Sutton, United Kingdom, SM2 5PT
    • Recruiting
    • The Royal Marsden Nhs Foundation Trust - Sutton

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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 non-amenable to surgery or other curative treatments or procedures.
• Must have disease progression on or after treatment with at least one prior systemic chemotherapy.
• Eastern Cooperative Oncology Group performance status score of 0 or 1.
• Life expectancy > 12 weeks.
• Willingness to avoid pregnancy.

Exclusion Criteria:

• Known additional malignancy that is progressing or requires active treatment.
• Central nervous system (CNS) metastases requiring treatment and/or leptomeningeal disease.
• Toxicity from prior therapy that has not recovered to protocol-defined limits.
• Prior receipt of an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent; treatment with an immune modulator (eg, CTLA-4, GITR, LAG3, TIM3, OX40, ICOS, IL-2, 4-1BB, CAR-T cell).
• Prior therapy with antiangiogenic small-molecule TKIs targeting the VEGF pathway
• 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 primary 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 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.
• Inadequate organ function.

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: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Escalation; Up to 6 doses of INCB099280 administered twice daily (BID) in combination with axitinib BID will be evaluated to identify dose(s) for further evaluation in the dose expansion phase of the study.	Drug: INCB099280; Administered as specified in the treatment arm description; Drug: axitinib; Administered as specified in the treatment arm description
Experimental: Part 2: Dose Expansion; On completion of Part 1, participants will be enrolled in 1 of 2 disease-specific cohorts: Cohort 1: Adults with clear-cell gynecological cancers with at least 50% clear-cell histology whose disease progressed on or following at least 1 prior line of systemic chemotherapy and are not candidates for curative surgery or (chemo)radiation. Cohort 2: Adults with rare histological subtype epithelial cancers of the gynecological tract whose disease progressed on or following at least 1 prior line of systemic chemotherapy and are not candidates for curative surgery or (chemo)radiation. One or two doses may be selected from Part 1 for each cohort in the Part 2 Expansion.	Drug: INCB099280; Administered as specified in the treatment arm description; Drug: axitinib; Administered as specified in the treatment arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of participants with Dose Limiting Toxicities (DLTs)	Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.	Up to 21 days
Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs)	Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.	Up to 2 years and 90 days
Part 1: Number of participants with TEAEs leading to dose modification	Number of participants with TEAEs leading to a dose modification (treatment interruption, dose reduction, and permanent discontinuation of either study drug).	Up to 2 years
Part 2: Objective response rate (ORR)	Defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), as determined by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Number of participants with Treatment-emergent Adverse Events (TEAEs)	Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.	Up to 2 years and 90 days
Part 2: Number of participants with TEAEs leading to dose modification	Number of participants with TEAEs leading to a dose modification (treatment interruption, dose reduction, and permanent discontinuation of either study drug).	Up to 2 years
Part 1: Objective response rate (ORR)	Defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), as determined by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Up to 2 years
Disease Control Rate (DCR)	Defined as the best overall response of CR, PR, or stable disease (SD) of at least 11 weeks from the start of treatment by investigator assessment per RECIST v1.1.	Up to 2 years
Duration of Response (DOR)	Defined as the time from the first CR or PR until disease progression by investigator assessment per RECIST v1.1 or death from any cause, whichever occurs earlier.	Up to 2 years
INCB099280 and axitinib plasma concentrations.	PK parameters will be calculated from the blood plasma concentrations of INCB099280 and axitinib using standard noncompartmental (model independent) PK methods.	Up to 2 years

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Philomena Colucci, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2024
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2027

Study Registration Dates

• First Submitted: July 10, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 18, 2023

Study Record Updates

• Last Update Posted (Estimated): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: tyrosine kinase inhibitor; combination therapy; ovarian cancer; fallopian tube cancer; cervical cancer; uterine cancer; carcinosarcoma; vaginal cancer; vulvar cancer; gynecologic tract cancer; primary peritoneum cancer; clear cell histology; mucinous adenocarcinoma; serous adenocarcinoma; neuroendocrine histology; small cell histology; small-molecule pdl1 inhibitor
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Axitinib
• Other Study ID Numbers: INCB99280-201; 2022-003663-13 (EudraCT Number: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes