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Trial record 1 of 1 for:    NCT02880371
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A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Array BioPharma
Sponsor:
Information provided by (Responsible Party):
Array BioPharma
ClinicalTrials.gov Identifier:
NCT02880371
First received: August 2, 2016
Last updated: March 2, 2017
Last verified: March 2017
  Purpose
This is an open-label, multicenter Phase 1b/2 study to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of ARRY-382 in combination with pembrolizumab in adult patients with selected advanced solid tumors (Part A), to assess the pharmacodynamic effects of the combination and to describe the preliminary antitumor activity of the combination in patients with advanced unresectable/metastatic melanoma (Part B), and to estimate the efficacy of the combination in patients with PD-L1-positive NSCLC (Part C).

Condition Intervention Phase
Advanced Solid Tumors
Drug: ARRY-382
Drug: Pembrolizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Study of ARRY-382 in Combination With Pembrolizumab, a Programmed Cell Death Receptor 1 (PD-1) Antibody, for the Treatment of Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Array BioPharma:

Primary Outcome Measures:
  • (Phase 1b/Part A) Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Cycle 1 (up to 21 days) ]
  • (Part B) Effect of the combination on circulating biomarkers of immune response [ Time Frame: Duration of Part B is approximately 2.5 years ]
  • (Part C) Efficacy of the combination in terms of the objective response rate [ Time Frame: Duration of Part C is approximately 1 year ]

Secondary Outcome Measures:
  • (Phase 1b/Part A, Part B) Preliminary antitumor activity of the combination in terms of objective response rate [ Time Frame: Phase 1b is expected to last until disease progression; Duration of Part B is approximately 2.5 years ]
  • (Phase 1b/Part A, Part B, Part C) Preliminary antitumor activity of the combination based on immune-related response criteria [ Time Frame: Phase 1b is expected to last until disease progression; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Phase 1b/Part A, Part B, Part C) Safety and tolerability of the combination in terms of adverse events and serious adverse events [ Time Frame: Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Part B) Evaluation of the pharmacodynamics of single-agent ARRY-382 in tumor tissue after 14 days of treatment in terms of immune biomarkers by IHC and/or RNA analysis [ Time Frame: Approximately 14 days ]
  • (Phase 1b/Part A, Part B, Part C) Preliminary antitumor activity of the combination in terms of duration of response [ Time Frame: Phase 1b is expected to last until disease progression; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Phase 1b/Part A, Part B, Part C) Preliminary antitumor activity of the combination in terms of progression-free survival [ Time Frame: Phase 1b is expected to last until disease progression; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Phase 1b/Part A, Part B, Part C) Preliminary antitumor activity of the combination in terms of overall survival [ Time Frame: Duration of Phase 1b is approximately 1 year; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Phase 1b/Part A, Part B, Part C) Evaluation of the plasma concentration-time profiles of ARRY-382 and its metabolites in the combination [ Time Frame: Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Phase 1b/Part A, Part B, Part C) Area under the plasma concentration-time curve over the dosing interval (AUCτ) of ARRY-382 and its three metabolites [ Time Frame: Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Phase 1b/Part A, Part B, Part C) Maximum plasma concentration (Cmax) of ARRY-382 and its three metabolites [ Time Frame: Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Phase 1b/Part A, Part B, Part C) Time of maximum observed plasma concentration (Tmax) of ARRY-382 and its three metabolites [ Time Frame: Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Phase 1b/Part A, Part B, Part C) Plasma concentration measured just before the next dose of study drug (Ctrough) of ARRY-382 and its three metabolites [ Time Frame: Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Phase 1b/Part A, Part B, Part C) Accumulation ratio based on AUC (RAUC) of ARRY-382 and its three metabolites [ Time Frame: Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Phase 1b/Part A, Part B, Part C) Metabolite-to-parent ratio based on AUC (MRAUC) of ARRY-382 and its three metabolites [ Time Frame: Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Phase 1b/Part A, Part B, Part C) Metabolite-to-parent ratio based on Cmax (MRCmax) of ARRY-382 and its three metabolites [ Time Frame: Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]
  • (Phase 1b/Part A, Part B, Part C) Accumulation ratio based on Cmax (RCmax) of ARRY-382 and its three metabolites [ Time Frame: Phase 1b: Patient safety will be evaluated throughout the treatment period, which is expected to last 6-10 months for each patient; Duration of Part B is approximately 2.5 years; Duration of Part C is approximately 1 year ]

Estimated Enrollment: 70
Study Start Date: August 2016
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A
Patients in Part A will receive escalating doses of single-agent ARRY-382 in combination with 2 mg/kg pembrolizumab.
Drug: ARRY-382
ARRAY-382 will be taken by mouth once daily at a fixed dose.
Drug: Pembrolizumab
Pembrolizumab will be administered intravenously over 30 minutes every 3 weeks.
Experimental: Part B
Patients in Part B will receive the RP2D dose of ARRY-382 determined during Part A in combination with 2 mg/kg pembrolizumab.
Drug: ARRY-382
ARRAY-382 will be taken by mouth once daily at a fixed dose.
Drug: Pembrolizumab
Pembrolizumab will be administered intravenously over 30 minutes every 3 weeks.
Experimental: Part C
Patients in Part C will receive the RP2D dose of ARRY-382 determined during Part A in combination with 200 mg pembrolizumab.
Drug: ARRY-382
ARRAY-382 will be taken by mouth once daily at a fixed dose.
Drug: Pembrolizumab
Pembrolizumab will be administered intravenously over 30 minutes every 3 weeks.

Detailed Description:

ARRY-382 is an inhibitor of CSF1R (colony-stimulating factor-1 receptor).

Each part of the study consists of a 28-day screening period, 21-day treatment cycles until disease progression, unacceptable toxicity, withdrawal of consent, or death (or other discontinuation criteria are met), and a 30-day safety follow-up period. Patients will be monitored for overall survival (OS) until 1 year after the date of the last patient's first visit.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

All Study Parts:

  • Personally signed and dated informed consent form
  • Diagnosis of cancer that has been histologically or cytologically confirmed
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1
  • For male patients and female patients of childbearing potential, agreement to use an effective method of contraception per institutional standards through 4 months after the last administration of study treatment (i.e., ARRY-382, pembrolizumab)
  • For females of childbearing potential only, negative serum human chorionic gonadotropin (hCG) pregnancy test result at baseline and nonlactating
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Part A (1 of the following):

  • Ovarian cancer, triple-negative breast cancer, head and neck squamous cell cancer, bladder cancer, metastatic colorectal cancer, pancreatic ductal adenocarcinoma, or gastric cancer that is measurable or evaluable, nonmeasurable as defined by RECIST v1.1 and meets 1 of the following criteria:

    • is refractory to standard of care
    • no standard therapy available
    • patient refuses standard therapy
  • Advanced, unresectable, or metastatic melanoma with or without prior treatment and measurable or evaluable, nonmeasurable disease as defined by RECIST v1.1
  • Advanced/metastatic PD-L1-positive NSCLC (defined as a tumor proportion score [TPS] ≥ 50%) with measurable or evaluable, non-measurable disease as defined by RECIST v1.1 and any of the following:

    • No prior systemic chemotherapy if tumor does not have EGFR or ALK genomic aberrations
    • Disease progression on or after platinum-containing chemotherapy;
    • If tumor has EGFR or ALK genomic aberrations, disease progression on an FDA-approved therapy for EGFR or ALK genomic tumor aberrations

Part B:

  • Advanced, unresectable, or metastatic melanoma with or without prior treatment, measurable disease as defined by RECIST v1.1, and a minimum of 3 lesions

Part C:

  • Advanced/metastatic PD-L1-positive NSCLC (defined as a TPS ≥ 50%) with measurable disease as defined by RECIST v1.1 (1 of the following):

    • No prior systemic chemotherapy if tumor does not have EGFR or ALK genomic aberrations
    • Disease progression on or after platinum-containing chemotherapy;
    • If tumor has EGFR or ALK genomic aberrations, disease progression on an FDA-approved therapy for EGFR or ALK genomic tumor aberrations

Key Exclusion Criteria:

  • Prior treatment as follows:

    • Part A: an immune CPI (e.g., PD-1, PD-L1, or cytotoxic T-lymphocyte antigen 4 [CTLA-4] inhibitor). NOTE: For patients with melanoma, prior treatment with ipilimumab is allowed if it was administered as adjuvant therapy and treatment was completed at least 3 months prior to enrollment.
    • Parts B: Prior treatment with a PD-1 or PD-L1-directed immune CPI or prior treatment with a CSF-1R inhibitor or CSF-1 (or MCSF) inhibitor. NOTE: Prior treatment with ipilimumab is allowed if it was administered as adjuvant therapy and treatment was completed at least 3 months prior to enrollment.
    • Part C:

      • Prior treatment with an immune CPI (e.g., PD-1, PD-L1, or CTLA-4 inhibitor) or a CSF-1R or CSF-1 (or MCSF) inhibitor
      • More than 1 prior systemic treatment for metastatic disease (disease relapse during treatment or within 6 months following adjuvant therapy will be considered metastatic disease)
  • Symptomatic brain metastasis at screening
  • Active autoimmune disease, documented history of autoimmune syndrome or disease, or a chronic medical condition that requires chronic steroid therapy or immunosuppressive medication
  • History of pneumonitis or interstitial lung disease
  • Severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study
  • Ocular melanoma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02880371

Contacts
Contact: Array BioPharma, Inc. 303-381-6604 clinicaltrials@arraybiopharma.com

Locations
United States, California
UCLA Department of Medicine Recruiting
Los Angeles, California, United States, 90095
Contact: Jonathan Goldman, MD    310-829-5471    jwgoldman@mednet.ucla.edu   
Principal Investigator: Jonathan Goldman, MD         
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States
Contact: Kayla Pacheco    720-724-8635    Kayla.Pacheco@UCDenver.edu   
Contact: Kim Walczyk    303-724-8633    Kimberly.Walczyk@UCDenver.edu   
Principal Investigator: Rene Gonzalez, M.D.         
United States, Indiana
Horizon Oncology Research, Inc. Recruiting
Lafayette, Indiana, United States, 47905
Contact: Sheri Akridge    765-446-5111 ext 19162    sakridge@horizonbioadvance.com   
Principal Investigator: Wael A. Harb, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Justin Gainor    617-724-4000    jgainor@partners.org   
Principal Investigator: Justin Gainor, MD         
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Edgar de la Cruz    313-576-8387    delacruz@karmanos.org   
Principal Investigator: Amy Weise, D.O.         
United States, Minnesota
Regions Hospital Recruiting
St. Paul, Minnesota, United States, 55101
Contact: Angie Martizna    651-254-1698    Angela.Martizna@ParkNicollet.com   
Principal Investigator: Arkadiusz Dudek, M.D.         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: ASKSarah Line    877-691-7274    asksarah@scresearch.net   
Principal Investigator: Melissa Johnson, MD         
United States, Texas
Texas Oncology, P.A., Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Charles L Cowey, MD    214-370-1000    C.Cowey@usoncology.com   
Principal Investigator: Charles L Cowey, MD         
United States, Utah
Utah Cancer Specialists Recruiting
Salt Lake City, Utah, United States, 84106
Contact: Johnny Walker    801-281-6864    jwalker@utahcancer.com   
Principal Investigator: Justin Call, MD         
Sponsors and Collaborators
Array BioPharma
Investigators
Study Director: Array BioPharma, Inc. 303-381-6604
  More Information

Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT02880371     History of Changes
Other Study ID Numbers: ARRAY-382-201
Study First Received: August 2, 2016
Last Updated: March 2, 2017

Keywords provided by Array BioPharma:
Advanced Solid Tumors
Pembrolizumab
ARRY-382

Additional relevant MeSH terms:
Pembrolizumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 25, 2017