NCT04580485CompletedPhase 1
A Phase 1, Open-Label, Multicenter Study of INCB106385 as Monotherapy or in Combination With Immunotherapy in Participants With Advanced Solid Tumors
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Incyte Corporation
- Enrollment
- 54
- Locations
- 27
- Primary Endpoint
- Number of treatment-emergent adverse events (TEAE)
Study Overview
Brief 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)
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
Open Label
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
- •ECOG performance status 0 to
- •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
Arms & Interventions
Treatment Group A (TGA) - INCB106385
Experimental
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.
Intervention: INCB106385 (Drug)
Treatment Group B (TGB) - INCB106385+INCMGA00012
Experimental
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.
Intervention: INCB106385 (Drug)
Treatment Group B (TGB) - INCB106385+INCMGA00012
Experimental
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.
Intervention: INCMGA00012 (Drug)
Outcomes
Primary Outcomes
Number of treatment-emergent adverse events (TEAE)
Time Frame: Up to Approximately 28 months
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.
Secondary Outcomes
- Cmin of INCB106385 as a single agent or in combination with INCMGA00012(Up to 6 months)
- Cmax of INCB106385 as a single agent or in combination with INCMGA00012(Up to 6 months)
- AUC of INCB106385 as a single agent or in combination with INCMGA00012(Up to 6 months)
- Tmax of INCB106385 as a single agent or in combination with INCMGA00012(Up to 6 months)
- Duration Of Response (DOR)(Up to approximately 24 months)
- Change in immune cell activation in tumors(Predose and Week 5-6)
- CL/F of INCB106385 as a single agent or in combination with INCMGA00012(Up to 6 months)
- Objective Response Rate (ORR)(Up to approximately 24 months)
- Disease Control Rate(Up to approximately 24 months)
- Change in tumoral gene expression(Predose and Week 5-6)
Investigators
Study Sites (27)
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