INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT04580485
• Recruitment Status: Completed
• First Posted: October 8, 2020
• Last Update Posted: March 8, 2024
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Tracking Information

• First Submitted Date: September 22, 2020
• First Posted Date: October 8, 2020
• Last Update Posted Date: March 8, 2024
• Actual Study Start Date: February 3, 2021
• Actual Primary Completion Date: February 22, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 6, 2020)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 8, 2020)

• Cmax of INCB106385 as a single agent or in combination with INCMGA00012 [ Time Frame: Up to 6 months ]
  Maximum observed plasma concentration.
• Tmax of INCB106385 as a single agent or in combination with INCMGA00012 [ Time Frame: Up to 6 months ]
  Time to maximum plasma concentration
• Cmin of INCB106385 as a single agent or in combination with INCMGA00012 [ Time Frame: Up to 6 months ]
  Minimum observed plasma concentration over the dose interval
• AUC of INCB106385 as a single agent or in combination with INCMGA00012 [ Time Frame: Up to 6 months ]
  Area under the plasma concentration-time curve
• CL/F of INCB106385 as a single agent or in combination with INCMGA00012 [ Time Frame: Up to 6 months ]
  Apparent oral dose clearance
• Objective Response Rate (ORR) [ Time Frame: Up to approximately 24 months ]
  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.
• Disease Control Rate [ Time Frame: Up to approximately 24 months ]
  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.
• Duration Of Response (DOR) [ Time Frame: Up to approximately 24 months ]
  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.
• Change in tumoral gene expression [ Time Frame: Predose and Week 5-6 ]
  Defined as the percent of patients with change in tumoral targeted gene expression compared to baseline
• Change in immune cell activation in tumors [ Time Frame: Predose and Week 5-6 ]
  Defined as the percent of patients demonstrating change in immune cell activation in tumors compared to baseline

Original Secondary Outcome Measures (submitted: October 6, 2020)

• Cmax of INCB106385 as a single agent or in combination with INCMGA00012 [ Time Frame: Up to 6 months ]
  Maximum observed plasma concentration.
• Tmax of INCB106385 as a single agent or in combination with INCMGA00012 [ Time Frame: Up to 6 months ]
  Time to maximum plasma concentration
• Cmin of INCB106385 as a single agent or in combination with INCMGA00012 [ Time Frame: Up to 6 months ]
  Minimum observed plasma concentration over the dose interval
• AUC of INCB106385 as a single agent or in combination with INCMGA00012 [ Time Frame: Up to 6 months ]
  Area under the plasma concentration-time curve
• CL/F of INCB106385 as a single agent or in combination with INCMGA00012 [ Time Frame: Up to 6 months ]
  Apparent oral dose clearance
• Objective Response Rate (ORR) [ Time Frame: Up to approximately 24 months ]
  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.
• Disease Control Rate [ Time Frame: Up to approximately 24 months ]
  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.
• Duration Of Response (DOR) [ Time Frame: Up to approximately 24 months ]
  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.
• Decreased tumoral gene expression [ Time Frame: Predose and Week 5-6 ]
  Defined as the percent of patients with decreased tumoral targeted gene expression compared to baseline
• Increased immune cell activation in tumors [ Time Frame: Predose and Week 5-6 ]
  Defined as the percent of patients demonstrating increased immune cell activation in tumors compared to baseline

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors
• Official Title: A Phase 1, Open-Label, Multicenter Study of INCB106385 as Monotherapy or in Combination With Immunotherapy in Participants With Advanced Solid Tumors
• 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)
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description:

Open Label

Primary Purpose: Treatment

Condition

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

Intervention

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

Study Arms

• Experimental: Treatment Group A (TGA) - INCB106385

  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: Drug: INCB106385
• Experimental: Treatment Group B (TGB) - INCB106385+INCMGA00012

  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.

  Interventions:

  • Drug: INCB106385
  • Drug: INCMGA00012

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 7, 2023): 54
• Original Estimated Enrollment (submitted: October 6, 2020): 230
• Actual Study Completion Date: February 22, 2024
• Actual Primary Completion Date: February 22, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Italy, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04580485
• Other Study ID Numbers: INCB 106385-102
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

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
• Supporting Materials: 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

• Current Responsible Party: Incyte Corporation
• Original Responsible Party: Same as current
• Current Study Sponsor: Incyte Corporation
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ilona Rybicka, M.D; Incyte Corporation

• PRS Account: Incyte Corporation
• Verification Date: March 2024