Clinical trial NCT04580485: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Keywords: INCB106385
Advanced Solid Tumors
PD-1
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2020-10-08
Enrollment: 54
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: 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)


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

Primary outcomes:
measure: Number of treatment-emergent adverse events (TEAE)
timeFrame: Up to Approximately 28 months
Secondary outcomes:
measure: Cmax of INCB106385 as a single agent or in combination with INCMGA00012
timeFrame: Up to 6 months
measure: Tmax of INCB106385 as a single agent or in combination with INCMGA00012
timeFrame: Up to 6 months
measure: Cmin of INCB106385 as a single agent or in combination with INCMGA00012
timeFrame: Up to 6 months
measure: AUC of INCB106385 as a single agent or in combination with INCMGA00012
timeFrame: Up to 6 months
measure: CL/F of INCB106385 as a single agent or in combination with INCMGA00012
timeFrame: Up to 6 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Disease Control Rate
timeFrame: Up to approximately 24 months
measure: Duration Of Response (DOR)
timeFrame: Up to approximately 24 months
measure: Change in tumoral gene expression
timeFrame: Predose and Week 5-6
measure: Change in immune cell activation in tumors
timeFrame: Predose and Week 5-6
Other outcomes:
Locations:
city: West Hollywood
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Baltimore
country: United States
facility: University of Maryland-Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
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: Brussels
country: Belgium
facility: Cliniques Universitaires Ucl Saint-Luc
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuis Leuven - Gasthuisberg
city: Bordeaux
country: France
facility: Institut Bergonie
city: Toulouse
country: France
facility: Universitaire Du Cancer de Toulouse Institut Claudius Regaud Iuct-Oncopole
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Modena
country: Italy
facility: A.O.U. Di Modena - Policlinico
city: Naples
country: Italy
facility: Istituto Nazionale Tumori Irccs Fondazione Pascale
city: Rozzano
country: Italy
facility: Irccs Istituto Clinico Humanitas
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma)
city: Barcelona
country: Spain
facility: Hospital General Universitario Vall D Hebron
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra (Cun)
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals Nhs Foundation Trust
city: Glasgow
country: United Kingdom
facility: University of Glasgow
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
Study officials:
affiliation: Incyte Corporation
name: Ilona Rybicka, M.D
role: STUDY_DIRECTOR
References: