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

NCT05949632 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: INCB99280-2012023-510281-27-002022-003663-13
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Advanced Solid Tumors

Keywords

gynecologic tract cancer; ovarian cancer; primary peritoneum cancer; fallopian tube cancer; uterine cancer; cervical cancer; vulvar cancer; vaginal cancer; clear cell histology; mucinous adenocarcinoma; carcinosarcoma; serous adenocarcinoma; neuroendocrine histology; small cell histology; small-molecule pdl1 inhibitor; tyrosine kinase inhibitor; combination therapy

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (6)

• Part 2: Number of participants with Treatment-emergent Adverse Events (TEAEs)

  Up to 2 years and 90 days

• Part 2: Number of participants with TEAEs leading to dose modification

  Up to 2 years

• Part 1: Objective response rate (ORR)

  Up to 2 years

• Disease Control Rate (DCR)

  Up to 2 years

• Duration of Response (DOR)

  Up to 2 years

Study Arms (2)

Part 1: Dose Escalation

EXPERIMENTAL

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; Drug: axitinib

Part 2: Dose Expansion

EXPERIMENTAL

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; Drug: axitinib

Interventions

INCB099280 DRUG

Administered as specified in the treatment arm description

Part 1: Dose Escalation; Part 2: Dose Expansion

axitinib DRUG

Administered as specified in the treatment arm description

Part 1: Dose Escalation; Part 2: Dose Expansion

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (6)

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Beatson West of Scotland Cancer Centrewester

Glasgow, G12 0YN, United Kingdom

Location

St Bartholomew'S Hospital

London, EC1A 7BE, United Kingdom

Location

Guys Hospital

London, SE1 9RT, United Kingdom

Location

The Royal Marsden

London, SW3 6JJ, United Kingdom

Location

The Royal Marsden Nhs Foundation Trust - Sutton

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Uterine Neoplasms; Uterine Cervical Neoplasms; Vulvar Neoplasms; Vaginal Neoplasms; Adenocarcinoma, Mucinous; Carcinosarcoma; Cystadenocarcinoma, Serous

Interventions

Axitinib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Uterine Diseases; Uterine Cervical Diseases; Vulvar Diseases; Vaginal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Cystic, Mucinous, and Serous; Neoplasms, Complex and Mixed; Sarcoma; Neoplasms, Connective and Soft Tissue; Cystadenocarcinoma

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Philomena Colucci

  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. In the Part 1 dose-escalation, participants will be enrolled in up to 6 dose levels of INCB099280 administered in combination with axitinib. In the Part 2 dose expansion, participants will be enrolled into 1 of 2 disease-specific cohorts at the dose(s) identified in Part 1.

Study Record Dates

• First Submitted: July 10, 2023
• First Posted: July 18, 2023
• Study Start: April 16, 2024
• Primary Completion: June 6, 2025
• Study Completion: June 6, 2025
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• 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.

Locations

GB (6)