Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

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

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), 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).

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: 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

Relevance to patient case: not relevant