INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors
- Conditions
- Non Small Cell Lung CancerCastration Resistant Prostate CancerColorectal CancerTriple Negative Breast CancerGastric/ Gastroesophageal JunctionSquamous Carcinoma of the Anal CanalSquamous Cell Carcinoma of Head and NeckPancreatic Ductal AdenocarcinomaOvarian CancerBladder Cancer
- Interventions
- Registration Number
- NCT04580485
- Lead Sponsor
- Incyte Corporation
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 54
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Group A (TGA) - INCB106385 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. Treatment Group B (TGB) - INCB106385+INCMGA00012 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. Treatment Group B (TGB) - INCB106385+INCMGA00012 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.
- Primary Outcome Measures
Name Time Method Number of treatment-emergent adverse events (TEAE) 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 Outcome Measures
Name Time Method Cmin of INCB106385 as a single agent or in combination with INCMGA00012 Up to 6 months Minimum observed plasma concentration over the dose interval
Cmax of INCB106385 as a single agent or in combination with INCMGA00012 Up to 6 months Maximum observed plasma concentration.
AUC of INCB106385 as a single agent or in combination with INCMGA00012 Up to 6 months Area under the plasma concentration-time curve
Tmax of INCB106385 as a single agent or in combination with INCMGA00012 Up to 6 months Time to maximum plasma concentration
Duration Of Response (DOR) 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 immune cell activation in tumors Predose and Week 5-6 Defined as the percent of patients demonstrating change in immune cell activation in tumors compared to baseline
CL/F of INCB106385 as a single agent or in combination with INCMGA00012 Up to 6 months Apparent oral dose clearance
Objective Response Rate (ORR) 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 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.
Change in tumoral gene expression Predose and Week 5-6 Defined as the percent of patients with change in tumoral targeted gene expression compared to baseline
Trial Locations
- Locations (27)
Cliniques Universitaires Ucl Saint-Luc
🇧🇪Brussels, Belgium
Cedars-Sinai Medical Center
🇺🇸West Hollywood, California, 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
Columbia University Medical Center
🇺🇸New York, New York, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
South Texas Accelerated Research Therapeutics
🇺🇸San Antonio, Texas, United States
Universitaire Ziekenhuis Leuven - Gasthuisberg
🇧🇪Leuven, Belgium
Institut Bergonie
🇫🇷Bordeaux, France
Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
🇫🇷Toulouse, France
Institut Gustave Roussy
🇫🇷Villejuif, France
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, Italy
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital General Universitario Vall D Hebron
🇪🇸Barcelona, Spain
Fundacion Jimenez Diaz University Hospital
🇪🇸Madrid, Spain
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Clinica Universidad de Navarra (Cun)
🇪🇸Pamplona, Spain
Cambridge University Hospitals Nhs Foundation Trust
🇬🇧Cambridge, United Kingdom
Guys and St Thomas Nhs Foundation Trust
🇬🇧London, United Kingdom
University of Glasgow
🇬🇧Glasgow, United Kingdom
Imperial College Healthcare Nhs Trust - Hammersmith Hospital
🇬🇧London, United Kingdom
The Christie Nhs Foundation Trust Uk
🇬🇧Manchester, United Kingdom