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

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

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).

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.

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