Clinical trial NCT04989387: Study of INCA 0186 in Subjects With Advanced Solid Tumors
Official title: A Phase 1, Open-Label, Multicenter Study of INCA00186 as Monotherapy or in Combination With Immunotherapy in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Gastrointestinal (GI) Malignancies
Keywords: open label
advanced solid tumors
squamous cell carcinoma of the head and neck
gastrointestinal malignancies
gastric/gastroesophageal junction cancer
hepatocellular carcinoma
pancreatic ductal adenocarcinoma
squamous carcinoma of the anal canal
colorectal cancer
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2021-08-04
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: This is an open-label, nonrandomized, multicenter, dose escalation, and dose expansion first-in human (FIH) Phase 1 study to determine the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of INCA00186 when given alone or in combination with INCB106385 and/or retifanlimab in participants with specific advanced solid tumors; squamous cell carcinoma of the head and neck (SCCHN) and specified gastrointestinal (GI) malignancies have been selected as indications of interest for this study. Participants with CD8 T-cell-positive tumors will be selected as these tumors are more likely to respond to immunotherapy.


Eligibility criteria: Inclusion Criteria:

* Ability to comprehend and willingness to sign a written ICF for the study.
* Male or female participant aged 18 years or older inclusive at the time of signing the ICF.
* Must be willing and able to conform to and comply with all Protocol requirements
* Willingness to undergo pre- and on-treatment tumor biopsy.
* Have CD8 T-cell-positive tumors
* ECOG performance status 0 or 1.
* Measurable disease according to RECIST v1.1.
* Participants with SCCHN: Participants with histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx not amenable to local therapy with curative intent (surgery or radiation with or without chemotherapy).
* Participants with specified GI malignancies: Histologically or cytologically confirmed advanced or metastatic colorectal (CRC), gastric/gastroesophageal junction (GEJ) cancer, hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), or squamous carcinoma of the anal canal (SCAC).
* Participants should have disease progression after treatment with available therapies, including anti-PD-(L)1 therapy (if applicable), that are known to confer clinical benefit or who are intolerant to or ineligible for standard treatment. Prior anti-PD-(L)1 therapy should not have been discontinued because of intolerance.
* For participants to be enrolled in cohorts including INCB106385: The ability to swallow oral medication.
* Willingness to avoid pregnancy or fathering children

Exclusion Criteria:

* Clinically significant cardiac disease, unstable angina, acute myocardial infarction within 6 months of Cycle 1 Day 1, and New York Heart Association Class III or IV congestive heart failure.
* History or presence of an ECG abnormality that, in the investigator's opinion, is clinically meaningful.
* Known active CNS metastases and/or carcinomatous meningitis.
* Participants who have active or inactive autoimmune disease or syndrome (eg, rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease) that has required systemic treatment in the past 2 years or who are receiving systemic therapy for an autoimmune or inflammatory disease (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
* 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 with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease free \> 1 year after treatment with curative intent.
* Participants with protocol specified exclusionary hematology, hepatic, renal and coagulation laboratory values at screening.

Has not recovered to ≤ Grade 1 from toxic effects of prior therapy (including prior immunotherapy) 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.
* Prior treatment with any adenosine pathway targeting drugs.
* 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.
* For participants to be enrolled in cohorts including INCB106385: concomitant treatment with strong CYP3A4 inhibitors or inducers.
* Receipt of a live virus 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.
* Known or suspected SARS-CoV-2 infection at the time of enrollment.
* Active HBV or HCV infection that requires treatment. HBV-DNA and HCV-RNA must be undetectable. Participants who have cleared a prior HBV infection (defined as HBsAg negative, HBsAg antibody positive, and anti-HBc antibody positive) are eligible for the study.
* Known history of HIV (HIV 1/2 antibodies).
* History of organ transplant, including allogeneic stem-cell transplantation or CAR-T cell therapy.
* Known hypersensitivity or severe reaction to any component of study drug(s) or formulation components.
* For participants to be enrolled in cohorts including INCB106385: Inability to swallow food or any concomitant condition of the upper GI tract that precludes administration of oral medications.
* Is pregnant or breastfeeding.
* Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
* The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code.

Primary outcomes:
measure: Evaluation of the safety and tolerability of INCA00186 as monotherapy and in combination with retifanlimab and/or INCB106385 as measured by the number of participants with adverse eventsductions and withdrawal of treatment due to AEs
timeFrame: 90 days after study completion totaling up to 27 months
measure: Evaluation of Dose-Limiting Toxicity (DLTs) of INCA00186 as monotherapy and in combination with retifanlimab and/or INCB106385 as measured by safety events during treatment
timeFrame: 90 days after study completion totaling up to 27 months
measure: Evaluation of Recommended Dose for Expansion (RDE) of INCA00186 as monotherapy and in combination with retifanlimab and/or INCB106385 as measured by safety, PK and PD data
timeFrame: 90 days after study completion totaling up to 27 months
Secondary outcomes:
measure: Determination of PK parameter Maximum Observed Plasma Concentration (Cmax) for INCA00186
timeFrame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
measure: Determination of PK parameter of Time to Maximum Plasma Concentration (tmax) for INCA00186
timeFrame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
measure: Determination of PK parameter of concentration at the end of the dosing interval (Ctau) for INCA00186
timeFrame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
measure: Determination of PK parameter of area under the plasma or serum concentration-time curve (AUC) for INCA00186
timeFrame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
measure: Determination of PK parameter of total clearance (CL) for INCA00186
timeFrame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
measure: Determination of PK parameter of volume of distribution (Vz) for INCA00186
timeFrame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
measure: Determination of PK parameter half-life (t1/2) for INCA00186
timeFrame: Cycle 1 days 1, 2, 8, 15, 22; Cycle 2 days 1, 8; Day 1 of every other cycle starting at Cycle 4 (ie, Cycle 4 day 1, Cycle 6 day 1, etc; each cycle is 28 days) + 30 day follow-up; approximately 24 months
measure: Intratumoral effect of INCA0186 on CD73 enzymatic activity
timeFrame: 2 biopsy samples will be taken: pre-treatment and on-treatment on Cycle 1 Day 22 (for every 2 week INCA00186 dosing group) or Cycle 2 Day 8 (for every 4 week INCA00186 dosing group); each cycle is 28 days; sampling will be taken within 2 months.
measure: Objective Response Rate (ORR) by radiographic disease assessment
timeFrame: Baseline through end of study up, to 24 months
measure: Disease Control Response (DCR) determined by radiographic disease assessment
timeFrame: Baseline through end of study, up to 24 months
measure: Duration of Response (DOR) from earliest date of disease response until earliest date of disease progression as determined by radiographic disease assessment, or death if occurring sooner than progression
timeFrame: Baseline through end of study, up to 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland-Greenebaum Cancer Center
state: Maryland
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Huntersville
country: United States
facility: Carolina Bio-Oncology Institute, Pllc
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Innsbruck
country: Austria
facility: Innsbruck University Hospital
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg
city: Brussels
country: Belgium
facility: Cliniques Universitaires Ucl Saint-Luc
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen (Uza)
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis (Uz) Leuven
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute Antoni Van Leeuwenhoek Ziekenhuis
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Mc Cancer Institute
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Barcelona
country: Spain
facility: Hospital General Universitario Vall D Hebron
city: Barcelona
country: Spain
facility: Institut Catala Doncologia Ico - Hospital Duran I Reynals Location
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de La Victoria
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals Nhs Foundation Trust
city: London
country: United Kingdom
facility: Guys and St Thomas Nhs Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare Nhs Trust - Hammersmith Hospital
city: Manchester
country: United Kingdom
facility: The Christie Nhs Foundation Trust Uk
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital Newcastle Upon Tyne Foundation Nhs Trust
city: Sutton
country: United Kingdom
facility: The Royal Marsden Nhs Foundation Trust - Chelsea
Study officials:
affiliation: Incyte Corporation
name: Ilona Rybicka, MD
role: STUDY_DIRECTOR
References: