A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies
- Conditions
- Advanced Solid Tumors
- Interventions
- Registration Number
- NCT03522142
- Lead Sponsor
- Incyte Corporation
- Brief Summary
The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and early clinical activity of single-agent INCB081776 (Part 1) and INCB081776 in combination with INCMGA00012 (Part 2).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 84
• Male and female participants at least 18 years of age with advanced malignancies who have received or been intolerant to standard therapy:
Parts 1A and 2A:
- Histologically confirmed advanced or metastatic gastric or GEJ adenocarcinoma, HCC, melanoma, NSCLC, RCC, soft-tissue sarcoma, SCCHN (recurrent or metastatic), TNBC, or urothelial carcinoma. Additional tumor histologies, including MSI-H tumors, may be allowed with approval from the medical monitor.
- Measurable disease per RECIST v1.1.
Parts 1B and 2B:
• Histologic confirmation of the cohort-specific tumor types specified below: Cohort 1 - Advanced or metastatic melanoma Cohort 2 - Advanced or metastatic NSCLC Cohort 3 - Recurrent or metastatic SCCHN Cohort 4 - Advanced or metastatic soft-tissue sarcoma
- Cohorts 1-3 must have received 1 prior PD-1/L1 treatment and have experienced PD during or after that treatment and have progressed on other SOC therapy(ies); Cohort 4 must be PD-1/L1 treatment naïve but have progressed on SOC therapy(ies).
- Measurable disease per RECIST v1.1.
- Must be willing to submit to a fresh baseline tumor biopsy and an on-treatment biopsy between Cycle 2 Day 1 and Cycle 3 Day 1.
- Care should be taken to biopsy the same lesion for the baseline and on-treatment samples. If a participant has a solitary target lesion, this should not be biopsied.
Part 1C:
- Participants with relapsed/refractory AML following standard therapy; acute promyelocytic leukemia (M3) and therapy-related AML are excluded.
- FLT3-ITD and IDH1/2 wild-type or mutated are eligible; appropriate targeted therapy for participants with actionable mutations must have been received.
- Laboratory values not within the protocol-defined range.
- History of retinal disease as defined in the protocol.
- Clinically significant cardiac disease as per protocol-defined criteria.
- History or presence of an ECG that, in the investigator's opinion, is clinically meaningful as per protocol-defined criteria.
- Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed as per protocol-defined criteria.
- Active or inactive autoimmune disease or syndrome that has required systemic treatment in the past 2 years or receiving systemic therapy for an autoimmune or inflammatory disease.
- Prior Grade 3 or higher immune-related AEs or any ocular toxicity on prior immunotherapy as per protocol-defined criteria.
- Receipt of any vitamin K antagonists, systemic corticosteroids, live vaccines, or treatment with any anticancer medications or investigational drugs within the protocol-defined intervals.
- Has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study treatment.
- Active infection requiring systemic therapy.
- Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
- Known history of HIV (HIV 1/2 antibodies).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description INCB081776 + INCMGA00012 INCMGA00012 INCB081776 in combination with INCMGA00012. INCB081776 INCB081776 Single-agent INCB081776. INCB081776 + INCMGA00012 INCB081776 INCB081776 in combination with INCMGA00012.
- Primary Outcome Measures
Name Time Method Part 2 (2A & B): RDE in combination with INCMGA00012 Up to one year Recommended dose as a combination as measured by safety, PK and data
Part 1 (1A and 1B): Recommended Dose for Expansion (RDE) Up to one year Recommended dose as a monotherapy as measured by safety, PK and data
Part 2 (2A & 2B): Number of treatment-emergent adverse events Screening through 90 days after end of treatment, up to approximately 1 year A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Part 1 (1A and 1B): Number of treatment-emergent adverse events (TEAEs) Screening through 90 days after end of treatment, up to approximately 1 year. A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.
- Secondary Outcome Measures
Name Time Method Part 1 and Part 2: Disease control rate Up to approximately 1 year. Defined as the percentage of participants having CR, PR, or stable disease (SD) per RECIST v1.1.
Part 1 and Part 2: Cmin of INCB081776 Up to approximately 3 weeks. Trough concentration of INCB081776
Part 1 and Part 2: Cmax of INCB081776 Up to approximately 3 weeks. Maximum observed plasma concentration.
Part 1 and Part 2: Pharmacokinetic/ pharmacodynamic correlation Up to approximately 3 weeks. To evaluate the correlation pharmacokinetic and pharmacodynamics of INCB081176
Part 1 and Part 2: Duration of response Up to approximately 1 year. Defined as the time from earliest date of disease response until the earliest date of disease progression (per RECIST v1.1) or death due to any cause, if occurring sooner than progression.
Part 1 and Part 2 : λz of INCB081776 Up to approximately 3 weeks. Terminal elimination rate constant
Part 1 and Part 2: Tmax of INCB081776 Up to approximately 3 weeks. Time to maximum plasma concentration.
Part 1 and Part 2: AUC0-t of INCB081776 Up to approximately 3 weeks. Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration
Part 1 and Part 2: t½ of INCB081776 Up to approximately 3 weeks. Apparent plasma terminal phase disposition half-life
Part 1 and Part 2: Overall response rate Up to approximately 1 year. Defined as the percentage of participants having complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Part 1 and Part 2: AUC0-∞ of INCB081776 Up to approximately 3 weeks. Area under the single-dose plasma concentration-time curve from Hour 0 to infinity
Part 1 and Part 2 : CL/F of INCB081776 Up to approximately 3 weeks. Oral dose clearance
Part 1 and Part 2 : Vz/F of INCB081776 Up to approximately 3 weeks. Apparent oral dose volume of distribution
Trial Locations
- Locations (18)
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of Pennsylvania Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Skane University Hospital Lund
🇸🇪Lund, Sweden
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Haukeland University Hospital
🇳🇴Bergen, Norway
Utprøvingsenheten, Oslo University Hospital Radiumhospitalet
🇳🇴Oslo, Norway
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Rigshospitalet Uni of Hospital of Copenhagen
🇩🇰Copenhagen, Denmark
Odense University Hospital
🇩🇰Odense C, Denmark
University of Wisconsin Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Karolinska University Hospital Solna
🇸🇪Stockholm, Sweden