INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors

Incyte

Status and phase: Completed; Phase 1

Conditions: Bladder Cancer; Squamous Carcinoma of the Anal Canal; Squamous Cell Carcinoma of Head and Neck; Hepatocellular Carcinoma; Gastric/ Gastroesophageal Junction; Pancreatic Ductal Adenocarcinoma; Non Small Cell Lung Cancer; Triple Negative Breast Cancer; Ovarian Cancer; Colorectal Cancer; Castration Resistant Prostate Cancer

Treatments: Drug: INCB106385; Drug: INCMGA00012

Study type: Interventional

Funder types: Industry

Identifiers

NCT04580485

INCB 106385-102

2020-002921-27 (EudraCT Number)

Details and patient eligibility

About

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)

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 2 patient groups

Treatment Group A (TGA) - INCB106385

Experimental group

Description:

In part 1 dose escalation, the dose levels will be escalated following a BOIN design. In part 2 dose expansion, participants will be assigned to different groups based on their tumor types and treated at the RDE.

Treatment:

Drug: INCB106385

Treatment Group B (TGB) - INCB106385+INCMGA00012

Experimental group

Description:

In part 1 dose escalation, the dose levels will be escalated following a BOIN design. In part 2 dose expansion, participants will be assigned to different groups based on their tumor types and treated at the RDE.

Treatment:

Drug: INCMGA00012

Drug: INCB106385