INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors

Colorectal Cancer Clinical Trial

Official title:

A Phase 1, Open-Label, Multicenter Study of INCB106385 as Monotherapy or in Combination With Immunotherapy in Participants With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04580485
• Other study ID #: INCB 106385-102
• Status: Completed
• Phase: Phase 1
• Start date: February 3, 2021
• Est. completion date: February 22, 2024

Study information

• Verified date: March 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, open-label, dose-escalation/dose-expansion Phase 1 clinical study to investigate the safety, tolerability, PK profile, pharmacodynamics, and preliminary clinical efficacy of INCB106385 when given as monotherapy or in combination with INCMGA00012 in participants with selected CD8 T-cell-positive advanced solid tumors including SCCHN, NSCLC, ovarian cancer, CRPC, TNBC, bladder cancer, and specified GI malignancies (defined as CRC, gastric/GEJ cancer, HCC, PDAC, or SCAC)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: February 22, 2024
• Est. primary completion date: February 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Ability to comprehend and willingness to sign an ICF.

• Willing and able to conform to and comply with all Protocol requirements.

• Histologically or cytologically confirmed advanced/metastatic SCCHN, NSCLC, ovarian cancer, TNBC, CRPC, bladder cancer, and specified GI malignancies (defined as CRC, gastric/GEJ cancer, HCC, PDAC, or SCAC) that progressed after treatment with available therapies (including anti PD-(L)1 therapy (if applicable).

• Willingness to undergo pre- and on-treatment tumor biopsy.

• Have CD8 T-cell-positive tumors.

• Presence of measurable disease according to RECIST v1.1.

• ECOG performance status 0 to 1.

• Life expectancy > 12 weeks.

• Willingness to avoid pregnancy or fathering children based.

• Acceptable laboratory parameters

Exclusion Criteria:

• Clinically significant cardiac disease.

• Known or active CNS metastases and/or carcinomatous meningitis.

• Active or inactive autoimmune disease or syndrome that required systemic treatment in the past 2 years or receiving systemic therapy for an autoimmune or inflammatory disease..

• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses > 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment.

• Known additional malignancy that is progressing or requires active treatment,or history of other malignancy within 2 years of the first dose of study treatment.

• Has not recovered to = Grade 1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study treatment.

• Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.

• Immune-related toxicity during prior immune therapy for which permanent discontinuation of therapy is recommended, or any immune-related toxicity requiring intensive or prolonged immunosuppression to manage.

• Any prior chemotherapy, biological therapy, or targeted therapy to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.

• Any prior radiation therapy within 28 days before the first dose of study treatment.

• Undergoing treatment with another investigational medication or having been treated with an investigational medication within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.

• Concomitant treatment with strong CYP3A4 inhibitors or inducers.

• Receipt of a live vaccine within 30 days of the first dose of study treatment.

• Infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week of the first dose of study treatment.

• Evidence of HBV or HCV infection or risk of reactivation.

• Known history of HIV (HIV 1/2 antibodies).

• History of organ transplant, including allogeneic stem-cell transplantation.

• Known hypersensitivity or severe reaction to any component of study drug(s) or formulation components.

• Presence of a gastrointestinal condition that may affect drug absorption.

• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.

• Any condition that would, in the investigator's judgment, interfere with full participation in the study,pose a significant risk to the participant; or interfere with interpretation of study data

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma
• Carcinoma, Squamous Cell
• Castration Resistant Prostate Cancer
• Colorectal Cancer
• Hepatocellular Carcinoma
• Non Small Cell Lung Cancer
• Ovarian Cancer
• Pancreatic Ductal Adenocarcinoma
• Squamous Cell Carcinoma of Head and Neck
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• INCB106385
INCB106385 will be administered orally QD
• INCMGA00012
INCMGA0012 will be administered IV once every 4 weeks (Q4W)

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Ucl Saint-Luc	Brussels
Belgium	Universitaire Ziekenhuis Leuven - Gasthuisberg	Leuven
France	Institut Bergonie	Bordeaux
France	Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole	Toulouse
France	Institut Gustave Roussy	Villejuif
Italy	A.O.U. Di Modena - Policlinico	Modena
Italy	Istituto Nazionale Tumori Irccs Fondazione Pascale	Naples
Italy	Irccs Istituto Clinico Humanitas	Rozzano
Italy	Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)	Verona
Spain	Hospital General Universitario Vall D Hebron	Barcelona
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Fundacion Jimenez Diaz University Hospital	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Clinica Universidad de Navarra (Cun)	Pamplona
United Kingdom	Cambridge University Hospitals Nhs Foundation Trust	Cambridge
United Kingdom	University of Glasgow	Glasgow
United Kingdom	Guys and St Thomas Nhs Foundation Trust	London
United Kingdom	Imperial College Healthcare Nhs Trust - Hammersmith Hospital	London
United Kingdom	The Christie Nhs Foundation Trust Uk	Manchester
United States	University of Maryland-Greenebaum Cancer Center	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Md Anderson Cancer Center	Houston	Texas
United States	Columbia University Medical Center	New York	New York
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	Cedars-Sinai Medical Center	West Hollywood	California

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Belgium,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of treatment-emergent adverse events (TEAE)	Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 90 days after last dose of study drug.	Up to Approximately 28 months
Secondary	Cmax of INCB106385 as a single agent or in combination with INCMGA00012	Maximum observed plasma concentration.	Up to 6 months
Secondary	Tmax of INCB106385 as a single agent or in combination with INCMGA00012	Time to maximum plasma concentration	Up to 6 months
Secondary	Cmin of INCB106385 as a single agent or in combination with INCMGA00012	Minimum observed plasma concentration over the dose interval	Up to 6 months
Secondary	AUC of INCB106385 as a single agent or in combination with INCMGA00012	Area under the plasma concentration-time curve	Up to 6 months
Secondary	CL/F of INCB106385 as a single agent or in combination with INCMGA00012	Apparent oral dose clearance	Up to 6 months
Secondary	Objective Response Rate (ORR)	Defined as the percentage of participants with a best overall response of CR or PR, as determined by investigator radiographic disease assessment according to RECIST v1.1.	Up to approximately 24 months
Secondary	Disease Control Rate	Defined as the percentage of participants with a best overall response of CR, PR, or SD, as determined by investigator radiographic disease assessment according to RECIST v1.1.	Up to approximately 24 months
Secondary	Duration Of Response (DOR)	Defined as the time from the earliest date of CR or PR until the earliest date of disease progression, as determined by investigator radiographic disease assessment according to RECIST v1.1, or death due to any cause if occurring sooner than progression.	Up to approximately 24 months
Secondary	Change in tumoral gene expression	Defined as the percent of patients with change in tumoral targeted gene expression compared to baseline	Predose and Week 5-6
Secondary	Change in immune cell activation in tumors	Defined as the percent of patients demonstrating change in immune cell activation in tumors compared to baseline	Predose and Week 5-6