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

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Incyte

Status and phase

Completed
Phase 2
Phase 1

Conditions

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

Treatments

Drug: INCB001158
Drug: Pembrolizumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT02903914
INCB 01158-101
Mk3475 Keynote 741 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

260 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Trial design

260 participants in 8 patient groups

INCB00158 was administered as monotherapy at 50mg twice daily
Experimental group
Description:
Monotherapy Part 1a: INCB001158 administered orally in patients with advanced/metastatic solid tumors. Escalating doses will be explored to determine the recommended phase 2 dose (RP2D).
Treatment:
Drug: INCB001158
INCB00158 was administered as monotherapy at 75mg twice daily
Experimental group
Description:
Monotherapy Part 2a: INCB001158 administered orally at the RP2D in patients with advanced/metastatic NSCLC (EGFR and Anaplastic Lymphoma Kinase (ALK) negative) previously treated with Standard of Care (SOC).
Treatment:
Drug: INCB001158
INCB00158 was administered as monotherapy at 100mg twice daily
Experimental group
Description:
Monotherapy Part 2b: INCB001158 administered orally at the RP2D in patients with advanced/metastatic CRC previously treated with SOC.
Treatment:
Drug: INCB001158
INCB00158 was administered as monotherapy at 150mg twice daily
Experimental group
Description:
Monotherapy Part 2c: INCB001158 administered orally at the RP2D in patients with Bladder Cancer, Gastric or Gastroesophageal Junction (GEJ) Cancer, Renal Cell Cancer (RCC), Squamous Cell Carcinoma of the Head and Neck (SCCHN), Urothelial Cell Cancer (UCC), or Melanoma, previously treated with SOC.
Treatment:
Drug: INCB001158
INCB00158 was administered in combination with pembroluzimab at 50mg twice daily
Experimental group
Description:
Monotherapy Part 2d: INCB001158 administered orally at the RP2D in patients with any tumor types in Parts 2a, 2b, or 2c.
Treatment:
Drug: INCB001158
INCB00158 was administered in combination with pembroluzimab at 75mg twice daily
Experimental group
Description:
Combination Part 1b: INCB001158 and Pembrolizumab administered in patients with advanced/metastatic NSCLC, Melanoma, Urothelial Cell Cancer, MSI CRC, MSS CRC, Gastric or Gastroesophageal Junction (GEJ) Cancer, SCCHN and Mesothelioma. Multiple dose levels will be explored to determine the recommended phase 2 dose (RP2D).
Treatment:
Drug: Pembrolizumab
Drug: INCB001158
INCB00158 was administered in combination with pembroluzimab at 100mg twice daily
Experimental group
Description:
Part 3a: INCB001158 and Pembrolizumab the combination RP2D in patients with advanced/metastatic NSCLC (EGFR and ALK negative) with disease progression on anti-PD-1 therapy or prolonged stable disease on Pembrolizumab in the immediate prior line of therapy.
Treatment:
Drug: Pembrolizumab
Drug: INCB001158
INCB001158 50 mg BID in combination with pembrolizumab
Experimental group
Description:
Part C: evaluated a reduced dose of INCB001158 50 mg BID in combination with pembrolizumab with patients with moderately impaired renal function.
Treatment:
Drug: Pembrolizumab
Drug: INCB001158

Trial documents
2

Trial contacts and locations

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Data sourced from clinicaltrials.gov

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