Clinical trial NCT03522142: A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies
Official title: A Phase 1a/1b Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Advanced solid tumors
AXL
MER
AXL/MER
PD-1
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2018-05-11
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

• 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.

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Part 1 (1A and 1B): Number of treatment-emergent adverse events (TEAEs)
timeFrame: Screening through 90 days after end of treatment, up to approximately 1 year.
measure: Part 1 (1A and 1B): Recommended Dose for Expansion (RDE)
timeFrame: Up to one year
measure: Part 2 (2A & 2B): Number of treatment-emergent adverse events
timeFrame: Screening through 90 days after end of treatment, up to approximately 1 year
measure: Part 2 (2A & B): RDE in combination with INCMGA00012
timeFrame: Up to one year
Secondary outcomes:
measure: Part 1 and Part 2: Cmax of INCB081776
timeFrame: Up to approximately 3 weeks.
measure: Part 1 and Part 2: Tmax of INCB081776
timeFrame: Up to approximately 3 weeks.
measure: Part 1 and Part 2: t½ of INCB081776
timeFrame: Up to approximately 3 weeks.
measure: Part 1 and Part 2: Pharmacokinetic/ pharmacodynamic correlation
timeFrame: Up to approximately 3 weeks.
measure: Part 1 and Part 2: Overall response rate
timeFrame: Up to approximately 1 year.
measure: Part 1 and Part 2: Disease control rate
timeFrame: Up to approximately 1 year.
measure: Part 1 and Part 2: Duration of response
timeFrame: Up to approximately 1 year.
measure: Part 1 and Part 2: AUC0-t of INCB081776
timeFrame: Up to approximately 3 weeks.
measure: Part 1 and Part 2: Cmin of INCB081776
timeFrame: Up to approximately 3 weeks.
measure: Part 1 and Part 2: AUC0-∞ of INCB081776
timeFrame: Up to approximately 3 weeks.
measure: Part 1 and Part 2 : CL/F of INCB081776
timeFrame: Up to approximately 3 weeks.
measure: Part 1 and Part 2 : λz of INCB081776
timeFrame: Up to approximately 3 weeks.
measure: Part 1 and Part 2 : Vz/F of INCB081776
timeFrame: Up to approximately 3 weeks.
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Copenhagen
country: Denmark
facility: Rigshospitalet Uni of Hospital of Copenhagen
city: Odense C
country: Denmark
facility: Odense University Hospital
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Utprøvingsenheten, Oslo University Hospital Radiumhospitalet
city: Lund
country: Sweden
facility: Skane University Hospital Lund
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Solna
Study officials:
affiliation: Incyte Corporation
name: Diane Hershock, MD
role: STUDY_DIRECTOR
References: