Clinical trial NCT02903914: Arginase Inhibitor INCB001158 as a Single Agent and in Combination With Immune Checkpoint Therapy in Patients With Advanced/Metastatic Solid Tumors
Official title: Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Oral Doses of the Arginase Inhibitor INCB001158 (Formerly Known as CB1158) as a Single Agent and in Combination With Immune Checkpoint Therapy in Patients With Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Cancer
Solid Tumors
Colorectal Cancer (CRC)
Gastric Cancer
Head and Neck Cancer
Lung Cancer
Renal Cell Carcinoma (RCC)
Bladder Cancer
UC (Urothelial Cancer)
Mesothelioma
Keywords: Immuno-Oncology
Checkpoint Inhibitors
Tumor Metabolism
Programmed cell death protein-1 (PD-1) inhibitor
Programmed death ligand 1 (PD-L1) inhibitor
Solid Tumors
RCC
MEL
NSCLC
Arginase
Arginase Inhibitor
INCB001158 (CB-1158)
SCCHN
GEJ
Immune Therapy
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2016-09-16
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: This study is an open-label Phase 1/Phase 2 evaluation of INCB001158 as a single agent and in combination with immune checkpoint therapy in patients with advanced/metastatic solid tumors.

Detailed description: This study is an open-label Phase 1 evaluation of INCB001158 as a single agent and in combination with immune checkpoint therapy in patients with advanced/metastatic solid tumors.

Single Agent INCB001158:

Patients with advanced/metastatic solid tumors will be enrolled into escalating monotherapy dose cohorts to determine the Recommended Phase 2 Dose (RP2D) of INCB001158. Additional patients with NSCLC, Colorectal Cancer (CRC), and other tumors including SCCHN, RCC, Gastric, Bladder and Melanoma will be enrolled at the single agent RP2D.

Combination Treatment:

Patients with advanced/metastatic NSCLC, Melanoma, Urothelial, Microsatellite Instability (MSI)/ Microsatellite Stable (MSS) CRC, Gastric, SCCHN and Mesothelioma will be enrolled into separate cohorts of combination therapy (INCB001158 and Pembrolizumab) to determine the RP2D.

In the dose expansion phase, additional patients with NSCLC, Melanoma, Urothelial, MSI/MSS CRC, Gastric, SCCHN and Mesothelioma will be treated with the combination of INCB001158 and Pembrolizumab at the RP2D.

All patients will be assessed for safety, pharmacokinetics, biomarkers and tumor response.

Eligibility criteria: \*Additional cohort specific criteria may apply

Inclusion Criteria:

* Must be age 18 or older
* Ability to provide written informed consent in accordance with federal, local, and institutional guidelines
* Histological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapy
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
* Life Expectancy of at least 3 months
* Adequate hepatic, renal (moderately impaired renal function in cohort 1c only), cardiac, and hematologic function
* Measurable disease by RECISTv1.1 criteria
* Resolution of treatment-related toxicities
* Willingness to avoid pregnancy or fathering children
* Prior anti-PD-1 treatment for combination dose expansion cohorts 1c, 3a - 3d

Exclusion Criteria:

* Currently pregnant or lactating
* Unable to receive oral medications
* Unable to receive oral or IV hydration
* Intolerance to prior anti-PD-1/PD-L1 therapy
* Prior anti-PD-1 treatment for combination dose expansion cohorts 1c, 3e - 3h
* Prior severe hypersensitivity reaction to another monoclonal antibody (mAb)
* Any other current or previous malignancy within 3 years except protocol allowed malignancies
* Chemotherapy, Tyrosine Kinase Inhibitor therapy, radiation therapy or hormonal therapy within 2 weeks
* Immunotherapy or biological therapy, or investigational agent within 3 weeks (Note: some cohort exceptions allow anti-PD-1 therapy)
* Active known or suspected exclusionary autoimmune disease
* Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other systemic immunosuppressive medications within 2 weeks
* Concomitant therapy with valproic acid/valproate-containing therapies
* Concomitant therapy with allopurinol and other xanthine oxidase inhibitors
* History of known risks factors for bowel perforation
* Symptomatic ascites or pleural effusion
* Major surgery within 28 days before Cycle 1 Day 1
* Active infection requiring within 2 weeks prior to first dose of study drug
* Patients who have HIV, Hepatitis B or C
* Conditions that could interfere with treatment or protocol-related procedures
* Active, non-stable brain metastases or CNS disease
* Known deficiencies or suspected defect in the urea cycle
* Received live-virus vaccination within 30 days (seasonal flu vaccine allowed if non-live virus)
* NSCLC with EGFR or ALK mutation

Primary outcomes:
measure: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
timeFrame: up to study completion (up to approximately 3.5 years)
Secondary outcomes:
measure: Recommended Phase 2 Dose (RP2D) of INCB001158
timeFrame: 12 weeks
measure: RP2D of INCB001158 in Combination With Pembrolizumab
timeFrame: 12 weeks
measure: Objective Response Rate (ORR)
timeFrame: Until disease progression/study discontinuation (up to approximately 5 years)
measure: Percentage of Participants With the Indicated Best Overall Response (BOR)
timeFrame: Until disease progression/study discontinuation (up to approximately 5 years)
measure: Duration of Response (DOR)
timeFrame: Until disease progression/study discontinuation (up to approximately 5 years)
measure: Progression-free Survival (PFS)
timeFrame: Until disease progression/study discontinuation (up to approximately 5 years)
measure: Cmax of INCB001158 Following Single Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
measure: Tmax of INCB001158 Following Single Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
measure: AUC0-t of INCB001158 Following Single Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
measure: AUC0-inf of INCB001158 Following Single Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
measure: t1/2 of INCB001158 Following Single Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
measure: CL/F of INCB001158 Following Single Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
measure: Vz/F of INCB001158 Following Single Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
measure: Cmax of INCB001158 Following Multiple Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Tmax of INCB001158 Following Multiple Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: AUC0-t of INCB001158 Following Multiple Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: AUC0-tau of INCB001158 Following Multiple Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: t1/2 of INCB001158 Following Multiple Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: CL/F of INCB001158 Following Multiple Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Vz/F of INCB001158 Following Multiple Escalating Doses for Part 1A
timeFrame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose
measure: Cmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food
timeFrame: Fasted: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose. Fed: Cycle 2 Day 8: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose
measure: Tmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food
timeFrame: Fasted: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose. Fed: Cycle 2 Day 8: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose
measure: AUC of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food
timeFrame: Fasted: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose. Fed: Cycle 2 Day 8: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose
measure: Cmax of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation
timeFrame: Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose
measure: Tmax of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation
timeFrame: Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose
measure: AUC0-t of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation
timeFrame: Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose
measure: AUC0-tau of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation
timeFrame: Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose
measure: Cmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A)
timeFrame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 (Part 1A only) hours post-dose.
measure: Tmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A)
timeFrame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 (Part 1A only) hours post-dose.
measure: AUC0-8h of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A)
timeFrame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Scottsdale
country: United States
facility: Honor Health/Pinnacle Oncology Hematology
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Washington
country: United States
facility: Georgetown
state: District of Columbia
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: BIDMC
state: Massachusetts
city: Boston
country: United States
facility: DFCI
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford
state: Michigan
city: Nashville
country: United States
facility: Sarah Cannon Research Institute at Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: San Antonio
country: United States
facility: START
state: Texas
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Siena
country: Italy
facility: Oncologica Azienda Ospedaliera Universitaria Senese
city: Amsterdam
country: Netherlands
facility: NKI
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia
city: Madrid
country: Spain
facility: START Madrid-HM CIOCC
Study officials:
affiliation: Calithera Biosciences, Inc
name: Emil Kuriakose, MD
role: STUDY_DIRECTOR
affiliation: Incyte Corporation
name: Sven Gogov, MD
role: STUDY_DIRECTOR
References: