Clinical Trial - NCT02880371

       

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

Active, not recruiting

Sponsor: Array BioPharma

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02880371

Protocol Info

Short Description: Phase 1b/2 ARRY-382 + Pembrolizumab in Advanced Solid Tumors
Long Description: A Phase 1b/2 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
MGH Status: Open
Sponsor: Array BioPharma Inc.
Disease Program: Phase I

Next Steps


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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/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).
Condition Title Intervention Phase
Advanced Solid Tumors ARRY-382 Pembrolizumab Phase 1/Phase 2
Study Type Interventional
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

Primary Outcome Measures

(Phase 1b/Part A) Incidence of dose-limiting toxicities (DLTs) [Time Frame: Cycle 1 (up to 21 days)] [Designated as safety issue: ]

(Phase 2) Efficacy of the combination in terms of the objective response rate (ORR) [Time Frame: Duration is approximately 2 years] [Designated as safety issue: ]


Secondary Outcome Measures

(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] [Designated as safety issue: ]

(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] [Designated as safety issue: ]

(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] [Designated as safety issue: ]

(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] [Designated as safety issue: ]

(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] [Designated as safety issue: ]

(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] [Designated as safety issue: ]

(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] [Designated as safety issue: ]

(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] [Designated as safety issue: ]

(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] [Designated as safety issue: ]

Estimated Enrollment: 90
Study Start Date: August 2016
Estimated Study Completion Date: April 2020
Estimated Primary Completion Date: April 2020
Arms Assigned Interventions

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.
Drug:Pembrolizumab
Pembrolizumab will be administered intravenously over 30 minutes every 3 weeks.

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.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Contacts and Locations

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

Locations

  • United States, California
    • UCLA Department of Medicine Los Angeles, California, United States, 90095
  • United States, Colorado
    • University of Colorado Aurora, Colorado, United States,
  • United States, Florida
    • Hematology Oncology Associates of the Treasure Coast Port Saint Lucie, Florida, United States, 34952
  • United States, Indiana
    • Horizon Oncology Research, Inc. Lafayette, Indiana, United States, 47905
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
  • United States, Michigan
    • Karmanos Cancer Institute Detroit, Michigan, United States, 48201
  • United States, Minnesota
    • Regions Hospital Saint Paul, Minnesota, United States, 55101
  • United States, Pennsylvania
    • Penn State Hershey Cancer Institute Hershey, Pennsylvania, United States, 17033-0850
  • United States, Tennessee
    • Sarah Cannon Research Institute Nashville, Tennessee, United States, 37203
  • United States, Texas
    • UT Health San Antonio Cancer Center San Antonio, Texas, United States, 78229
  • United States, Utah
    • Utah Cancer Specialists Salt Lake City, Utah, United States, 84106
  • United States, Washington
    • Northwest Medical Specialties Tacoma, Washington, United States, 98405

Sponsors and Collaborators

Array BioPharma

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02880371
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Array BioPharma:

Advanced Solid Tumors

Pembrolizumab

ARRY-382

CSF-1R

CSF1R

cfms

Additional relevant MeSH terms:

Pembrolizumab

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019