Clinical Trials /

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

NCT02880371

Description:

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).

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Colorectal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: ARRAY-382-201
  • SECONDARY ID: C4261001
  • NCT ID: NCT02880371

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
ARRY-382Phase 1b/Part A
PembrolizumabPhase 1b/Part A

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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1b/Part AExperimentalPatients in Part A will receive escalating doses of single-agent ARRY-382 in combination with 2 mg/kg pembrolizumab.
  • ARRY-382
  • Pembrolizumab
Phase 2ExperimentalPatients in Phase 2 will receive the MTD/RP2D dose of ARRY-382 determined during Part A in combination with 200mg pembrolizumab.
  • ARRY-382
  • Pembrolizumab

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:(Phase 1b/Part A) Incidence of dose-limiting toxicities (DLTs)
Time Frame:Cycle 1 (up to 21 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:(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
Safety Issue:
Description:
Measure:(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
Safety Issue:
Description:
Measure:(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
Safety Issue:
Description:
Measure:(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
Safety Issue:
Description:
Measure:(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
Safety Issue:
Description:
Measure:(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
Safety Issue:
Description:
Measure:(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
Safety Issue:
Description:
Measure:(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
Safety Issue:
Description:
Measure:(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
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Pfizer

Trial Keywords

  • Advanced Solid Tumors
  • Pembrolizumab
  • ARRY-382
  • CSF-1R
  • CSF1R
  • cfms

Last Updated

March 22, 2021