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A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02880371
Recruitment Status : Active, not recruiting
First Posted : August 26, 2016
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
Array BioPharma

Tracking Information
First Submitted Date  ICMJE August 2, 2016
First Posted Date  ICMJE August 26, 2016
Last Update Posted Date April 17, 2019
Study Start Date  ICMJE August 2016
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2018)
  • (Phase 1b/Part A) Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Cycle 1 (up to 21 days) ]
  • (Phase 2) Efficacy of the combination in terms of the objective response rate (ORR) [ Time Frame: Duration is approximately 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 23, 2016)
  • (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 ]
Change History Complete list of historical versions of study NCT02880371 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 10, 2018)
  • (Phase 1b/Part A) Preliminary antitumor activity of the combination in terms of objective response rate (ORR) [ Time Frame: Phase 1b is expected to last until disease progression ]
  • (Phase 1b/Part A, Phase 2) Duration of response (DOR) [ Time Frame: Phase 1b is expected to last until disease progression; Duration of Phase 2 is approximately 2 years ]
  • (Phase 1b/Part A, Phase 2) Progression-free survival (PFS) [ Time Frame: Phase 1b is expected to last until disease progression; Duration of Phase 2 is approximately 2 years ]
  • (Phase 1b/Part A, Phase 2) Overall survival (OS) [ Time Frame: Duration of Phase 1b is approximately 1 year; Duration of Phase 2 is approximately 2 years ]
  • (Phase 1b/Part A, Phase 2) Immune-related response criteria (irRR) [ Time Frame: Phase 1b is expected to last until disease progression; Duration of Phase 2 is approximately 2 years ]
  • (Phase 1b/Part A, Phase 2) Immune-related progression-free survival (irPFS) [ Time Frame: Phase 1b is expected to last until disease progression; Duration of Phase 2 is approximately 2 years ]
  • (Phase 1b/Part A, Phase 2) 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 Phase 2 is approximately 2 years ]
  • (Phase 1b/Part A, Phase 2) 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 Phase 2 is approximately 2 years ]
  • (Phase 1b/Part A, Phase 2) Trough concentrations and pharmacokinetics (AUC, Cmax, Tmax, accumulation ratio and metabolite-to-parent ratio) for ARRY-382 and its three metabolites [ Time Frame: 6 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 23, 2016)
  • (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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors
Official Title  ICMJE 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
Brief Summary 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/Phase 1b); and to estimate the efficacy of the combination in three separate cohorts: 1) patients with advanced solid tumors that have progressed on prior PD-1/PD-L1inhibitors, 2) patients with platinum-resistant ovarian cancer and 3) patients with pancreatic ductal adenocarcinoma (Phase 2).
Detailed Description

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

Each phase of the study consists of a 28-day screening period; 21-day treatment cycles with the combination of ARRY-382 and pembrolizumab until disease progression as determined by the Investigator, unacceptable toxicity, withdrawal of consent, or death (or other discontinuation criteria are met), and a 30-day safety follow-up period. Patients in all cohorts/phases will be monitored for overall survival (OS) until 1 year after the date of the last patient's first visit.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • Experimental: Phase 1b/Part A
    Patients in Part A will receive escalating doses of single-agent ARRY-382 in combination with 2 mg/kg pembrolizumab.
    Interventions:
    • Drug: ARRY-382
    • Drug: Pembrolizumab
  • Experimental: Phase 2
    Patients in Phase 2 will receive the MTD/RP2D dose of ARRY-382 determined during Part A in combination with 200mg pembrolizumab.
    Interventions:
    • Drug: ARRY-382
    • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: May 10, 2018)
90
Original Estimated Enrollment  ICMJE
 (submitted: August 23, 2016)
70
Estimated Study Completion Date  ICMJE April 2020
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria

All Study Parts:

  • Diagnosis of cancer that has been histologically or cytologically confirmed
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1

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 (1 of the following):

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

Phase 2 (1 of the following):

  • Advanced/metastatic solid tumor with PD as defined by RECIST 1.1 or irRC on an anti-PD-1- or anti-PD-L1-containing regimen as their most recent prior therapy
  • Advanced/metastatic epithelial ovarian cancer, peritoneal cancer or tubal cancer with measurable disease as defined by RECIST 1.1, that had progressed within 6 months of completing ≥ 4 cycles of platinum-based therapy
  • Advanced/metastatic PDA that is locally advanced, unresectable or metastatic with measurable disease as defined by RECIST v1.1 in patients who have received at least one prior line of systemic therapy for their disease

Key Exclusion Criteria

  1. 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.

    • Phase 2:

      • A CSF-1R inhibitor or CSF-1 (or MCSF) inhibitor.
      • prOVCA and PDA patients only: an immune CPI (e.g., PD-1, PD-L1, or CTLA-4 inhibitor)
  2. Symptomatic brain metastasis at screening
  3. Active autoimmune disease, documented history of autoimmune syndrome or disease, or a chronic medical condition that requires chronic steroid therapy or immunosuppressive medication
  4. History of pneumonitis or interstitial lung disease
  5. 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
  6. Ocular melanoma
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02880371
Other Study ID Numbers  ICMJE ARRAY-382-201
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Array BioPharma
Study Sponsor  ICMJE Array BioPharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Array BioPharma, Inc. 303-381-6604
PRS Account Array BioPharma
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP