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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02903914
• Other study ID #: INCB 01158-101
• Secondary ID: Mk3475 Keynote 7
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 14, 2016
• Est. completion date: August 15, 2022

Study information

• Verified date: February 2023
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 260
• Est. completion date: August 15, 2022
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Renal Cell
• Colorectal Cancer (CRC)
• Gastric Cancer
• Head and Neck Cancer
• Lung Cancer
• Mesothelioma
• Metastatic Cancer
• Renal Cell Carcinoma (RCC)
• Solid Tumors
• UC (Urothelial Cancer)

Intervention

Drug:
• INCB001158
Arginase Inhibitor
• Pembrolizumab
PD-1 Inhibitor

Locations

Country	Name	City	State
Italy	Ospedale San Raffaele	Milan
Italy	Oncologica Azienda Ospedaliera Universitaria Senese	Siena
Netherlands	NKI	Amsterdam
Netherlands	Radboudumc	Nijmegen
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Institut Catala d'Oncologia	Barcelona
Spain	START Madrid-HM CIOCC	Madrid
United States	Johns Hopkins	Baltimore	Maryland
United States	BIDMC	Boston	Massachusetts
United States	DFCI	Boston	Massachusetts
United States	Henry Ford	Detroit	Michigan
United States	MD Anderson	Houston	Texas
United States	MD Anderson	Houston	Texas
United States	University of South Alabama	Mobile	Alabama
United States	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee
United States	Vanderbilt	Nashville	Tennessee
United States	START	San Antonio	Texas
United States	Honor Health/Pinnacle Oncology Hematology	Scottsdale	Arizona
United States	University of Arizona	Tucson	Arizona
United States	Georgetown	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Italy,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of the Safety and Tolerability of INCB001158 as a Single Agent and in Combination With Pembrolizumab: Incidence of Adverse Events	Evaluation of adverse events (AEs) and changes in laboratory values, vital signs, and physical examinations.	Up to 6 months
Secondary	Recommended Phase 2 Dose (RP2D) of INCB001158	RP2D was determined by a traditional 3+3 dose escalation design of single agent INCB001158 in patients with advanced/metastatic solid tumors at doses 50, 75, 100 or 150 mg.	12 Weeks
Secondary	Recommended Phase 2 Dose (RP2D) of INCB001158 in Combination With Pembrolizumab	INCB001158 was dosed orally BID	12 Weeks
Secondary	Overall Response Rate (ORR) Anti-tumor Activity of INCB001158 as Monotherapy and in Combination With Pembrolizumab for Patients With Advanced/Metastatic Solid Tumors	ORR assessment of anti-tumor activity per RECIST Criteria (v1.1) and immune-related RECIST (irRECIST) criteria.	Until disease progression/study discontinuation up to 24 months
Secondary	Best Overall Response (BOR) Anti-tumor Activity of INCB001158 as Monotherapy and in Combination With Pembrolizumab for Patients With Advanced/Metastatic Solid Tumors	BOR Assessment of anti-tumor activity per RECIST Criteria (v1.1) and immune-related RECIST (irRECIST) criteria.	Until disease progression/study discontinuation up to 24 months
Secondary	Duration of Response (DOR) Anti-tumor Activity of INCB001158 as Monotherapy and in Combination With Pembrolizumab for Patients With Advanced/Metastatic Solid Tumors	DOR Assessment of anti-tumor activity per RECIST Criteria (v1.1) and immune-related RECIST (irRECIST) criteria.	Until disease progression/study discontinuation up to 24 months
Secondary	Progression-free Survival (PFS) Anti-tumor Activity of INCB001158 as Monotherapy and in Combination With Pembrolizumab for Patients With Advanced/Metastatic Solid Tumors	DOR Assessment of anti-tumor activity per RECIST Criteria (v1.1) and immune-related RECIST (irRECIST) criteria.	Until disease progression/study discontinuation up to 24 months
Secondary	Pharmacokinetics: Cmax of INCB001158	Non-compartmental method of analysis will be used to analyze the plasma concentrations of INCB001158. in patients with CrCl 30-49 mL/min (Part 1c only) or CrCl = 50 mL/min (Parts 1a, 1b, 2, and 3)	Cycle 1 Day 1 (C1D1), C1D15, C2D! + 2, C4D1
Secondary	Tmax Plasma Pharmacokinetic (PK) Profile of INCB001158	Non-compartmental method of analysis will be used to analyze the plasma concentrations of INCB001158.	12 Weeks
Secondary	AUCt Plasma Pharmacokinetic (PK) Profile of INCB001158	Non-compartmental method of analysis will be used to analyze the plasma concentrations of INCB001158.	12 Weeks
Secondary	AUC0-12 Plasma Pharmacokinetic (PK) Profile of INCB001158	Non-compartmental method of analysis will be used to analyze the plasma concentrations of INCB001158.	12 Weeks
Secondary	CL/F Plasma Pharmacokinetic (PK) Profile of INCB001158	Non-compartmental method of analysis will be used to analyze the plasma concentrations of INCB001158.	12 Weeks