A Phase 1/2 Study of INCB001158 in Combination With Chemotherapy in Subjects With Solid Tumors

• ClinicalTrials.gov Identifier: NCT03314935
• Recruitment Status: Active, not recruiting
• First Posted: October 19, 2017
• Last Update Posted: July 21, 2022
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Study Description

Brief Summary:

The purpose of this open-label nonrandomized Phase 1/2 study is to evaluate INCB001158 in combination with chemotherapy in participants with advanced/metastatic solid tumors.

Condition or disease	Intervention/treatment	Phase
Biliary Tract Cancer (BTC); Colorectal Cancer (CRC); Endometrial Cancer; Gastroesophageal Cancer (GC); Ovarian Cancer; Solid Tumors	Drug: INCB001158; Drug: Oxaliplatin; Drug: Leucovorin; Drug: 5-Fluorouracil; Drug: Gemcitabine; Drug: Cisplatin; Drug: Paclitaxel	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 149 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of INCB001158 in Combination With Chemotherapy, in Subjects With Advanced or Metastatic Solid Tumors
• Actual Study Start Date: November 21, 2017
• Estimated Primary Completion Date: December 30, 2022
• Estimated Study Completion Date: December 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment Group A; INCB001158 + FOLFOX	Drug: INCB001158; Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1.; Other Name: Arginase inhibitor; Drug: Oxaliplatin; Oxaliplatin administered intravenously at the protocol-defined dose and schedule.; Drug: Leucovorin; Leucovorin at the protocol-defined dose and regimen.; Drug: 5-Fluorouracil; 5-Fluorouracil at the protocol-defined dose and regimen.
Experimental: Treatment Group B; INCB001158 + gemcitabine/cisplatin	Drug: INCB001158; Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1.; Other Name: Arginase inhibitor; Drug: Gemcitabine; Gemcitabine at the protocol-defined dose and regimen.; Drug: Cisplatin; Cisplatin at the protocol-defined dose and regimen.
Experimental: Treatment Group C; INCB001158 + paclitaxel	Drug: INCB001158; Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1.; Other Name: Arginase inhibitor; Drug: Paclitaxel; Paclitaxel at the protocol-defined dose and regimen.

Outcome Measures

Primary Outcome Measures :

1. Phase 1: Participants with treatment-emergent adverse events (TEAE) [ Time Frame: 28 days ]
   TEAE is defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
2. Phase 2: Objective response rate [ Time Frame: Every 8 weeks for duration of study participation which is estimated to be 18 months. ]
   Defined as the percentage of subjects having a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Secondary Outcome Measures :

1. Phase 2: Participants with TEAEs [ Time Frame: Screening through 90 days after end of treatment, up to 21 months. ]
   TEAE is defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
2. Phase 1: Objective response rate [ Time Frame: Every 8 weeks for duration of study participation, up to 18 months. ]
   Defined as the percentage of subjects having a CR or PR per RECIST v1.1.
3. Duration of response [ Time Frame: Every 8 weeks for duration of study participation, up to 18 months. ]
   Defined as the time from earliest date of CR or PR (per RECIST v1.1) until the earliest date of disease progression or death due to any cause, if occurring sooner than disease progression.
4. Disease control rate [ Time Frame: Every 8 weeks for duration of study participation, up to 18 months. ]
   Defined as the percentage of subjects having CR, PR, or stable disease for at least 8 weeks (per RECIST v1.1).
5. Progression-free survival [ Time Frame: Every 8 weeks for duration of study participation, up to 18 months ]
   Defined as the time from date of first dose of study drug until the earliest date of disease progression (per RECIST v1.1) or death due to any cause, if occurring sooner than progression.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors.
• Presence of measurable disease per RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Baseline archival tumor specimen available or willingness to undergo a pretreatment tumor biopsy to obtain the specimen.
• Resolution of treatment-related toxicities.
• Adequate hepatic, renal, cardiac, and hematologic function.
• Additional cohort-specific criteria may apply.

Exclusion Criteria:

• Subjects who participated in any other study in which receipt of an investigational study drug or device occurred within 28 days or 5 half-lives (whichever is longer) prior to first dose.
• Has received a prior monoclonal antibody within 4 weeks or 5 half-lives (whichever is shorter) before administration of study drug.
• Has had prior chemotherapy or targeted small molecule therapy within 2 weeks before administration of study treatment.
• Has received prior approved radiotherapy within 14 days of study therapy.
• Has had known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry.
• Has an active autoimmune disease that has required systemic treatment in past 2 years.
• Has an active infection requiring systemic therapy.
• Has known active CNS metastases and/or carcinomatous meningitis.
• Women who are pregnant or breastfeeding.

Contacts and Locations

Locations

United States, Alabama

University of Alabama

Birmingham, Alabama, United States, 35294-3300

USA Mitchell Cancer Center

Mobile, Alabama, United States, 36604

United States, California

UC Davis - Comprehensive Cancer Centre

Sacramento, California, United States, 95817

United States, Georgia

Northwest Georgia Oncology Centers

Marietta, Georgia, United States, 30060

United States, Texas

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

START San Antonio

San Antonio, Texas, United States, 78229

Belgium

Grand Hopital de Charleroi - Department of Medical Oncology

Brussels, Belgium, 6000

Institut Jules Bordet - Clinical Trials Conduct Unit

Brussels, Belgium, B-1000

United Kingdom

UCL Cancer Institute

London, United Kingdom, WC1E 6BT

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Sponsors and Collaborators

Incyte Corporation

Investigators

• Study Director: Lance Leopold, MD; Incyte Corporation

More Information

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT03314935
• Other Study ID Numbers: INCB 01158-203
• First Posted: October 19, 2017
• Last Update Posted: July 21, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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

• Supporting Materials: Study Protocol; Statistical Analysis Plan (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.
• URL: https://www.incyte.com/our-company/compliance-and-transparency

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Incyte Corporation:

INCB001158; arginase inhibitor; oxaliplatin; leucovorin; 5 fluorouracil; gemcitabine; cisplatin; paclitaxel; solid tumors; colorectal cancer; biliary tract cancer; gastroesophageal cancer; endometrial cancer; ovarian cancer

Additional relevant MeSH terms:

Colorectal Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms; Biliary Tract Neoplasms; Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Biliary Tract Diseases; Leucovorin; Gemcitabine; Paclitaxel; Fluorouracil; Oxaliplatin; Antineoplastic Agents, Phytogenic