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Brief Title: Arginase Inhibitor INCB001158 as a Single Agent and in Combination With Immune Checkpoint Therapy in Patients With Advanced/Metastatic Solid Tumors

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

INTRODUCTION

  • Org Study ID: INCB 01158-101
  • Secondary ID: Mk3475 Keynote 741
  • NTC ID: NCT02903914
  • Sponsor: Incyte Corporation

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.


  • Overall Status
    Recruiting
  • Start Date
    September 14, 2016
  • Phase
    Phase 1/Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Safety and Tolerability of INCB001158 as a single agent and in combination with Pembrolizumab: Incidence of Adverse Events

Primary Outcome 1 - Timeframe: Every 28 days (single agent INCB001158) or 21 days (INCB001158 in combination with Pembrolizumab) from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months

CONDITION

  • 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

ELIGIBILITY


*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

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Emil Kuriakose, MD

Role: Study Director

Affiliation: Calithera Biosciences, Inc

Overall Contact

Name: Emil Kuriakose, MD

Phone: 1.855.463.3463

Email: medinfo@incyte.com

LOCATION

Facility Status Contact
Facility: University of South Alabama
Mobile, Alabama 36604
United States
Status: Recruiting Contact: N/A
Facility: Honor Health/Pinnacle Oncology Hematology
Scottsdale, Arizona 85258
United States
Status: Recruiting Contact:
Stephanie Althoff

Facility: University of Arizona
Tucson, Arizona 85719
United States
Status: Recruiting Contact: N/A
Facility: Georgetown
Washington, District of Columbia 20007
United States
Status: Recruiting Contact: N/A
Facility: Johns Hopkins
Baltimore, Maryland 21287
United States
Status: Recruiting Contact: N/A
Facility: BIDMC
Boston, Massachusetts 02215
United States
Status: Recruiting Contact: N/A
Facility: DFCI
Boston, Massachusetts 02215
United States
Status: Recruiting Contact: N/A
Facility: Henry Ford
Detroit, Michigan 48202
United States
Status: Recruiting Contact: N/A
Facility: Sarah Cannon Research Institute at Tennessee Oncology
Nashville, Tennessee 37203
United States
Status: Recruiting Contact:
Erin Fisher

Facility: Vanderbilt
Nashville, Tennessee 37232
United States
Status: Recruiting Contact: N/A
Facility: MD Anderson
Houston, Texas 77230-1402
United States
Status: Recruiting Contact:
Yan Zhang, MD, PhD

Facility: MD Anderson
Houston, Texas 77230
United States
Status: Recruiting Contact: N/A
Facility: START
San Antonio, Texas 78229
United States
Status: Recruiting Contact:
Edwin Blanco-Cepeda, RN

Facility: Ospedale San Raffaele
Milan, 20132
Italy
Status: Recruiting Contact: N/A
Facility: Oncologica Azienda Ospedaliera Universitaria Senese
Siena, 53100
Italy
Status: Recruiting Contact: N/A
Facility: NKI
Amsterdam, 1066 CX
Netherlands
Status: Recruiting Contact: N/A
Facility: Radboudumc
Nijmegen, HP 452
Netherlands
Status: Recruiting Contact: N/A
Facility: Hospital Universitari Vall d'Hebron
Barcelona, 8035
Spain
Status: Recruiting Contact: N/A
Facility: Institut Catala d'Oncologia
Barcelona, 8908
Spain
Status: Recruiting Contact: N/A
Facility: START Madrid-HM CIOCC
Madrid, 28050
Spain
Status: Recruiting Contact: N/A