Patient case: 86-year-old female with melanoma; genetic feature: high tumor mutational burden

Clinical trial: Arginase Inhibitor CB-1158 in Patients With Solid Tumors

Summary: This study is an open-label Phase 1 evaluation of CB-1158 as a single agent and in combination with immune checkpoint therapy in patients with advanced/metastatic solid tumors.

Detailed description: This study is an open-label Phase 1 evaluation of CB-1158 as a single agent and in combination with immune checkpoint therapy in patients with advanced/metastatic solid tumors.
  Single Agent CB-1158:
  Patients with advanced/metastatic solid tumors be enrolled into escalating monotherapy dose cohorts to determine the Recommended Phase 2 Dose (RP2D) of CB-1158. Additional patients with NSCLC, CRC, and other tumors will be enrolled at the single agent RP2D.
  Combination Treatment:
  Patients with advanced/metastatic clear cell renal cell carcinoma, melanoma, and non-small cell lung cancer and other solid tumors previously treated with a PD-1 and PD-L1 therapy will be enrolled into separate cohorts of combination therapy (CB-1158 and nivolumab) to determine the RP2D. Additional patients with NSCLC and melanoma will be enrolled at the combination of CB-1158 with nivolumab at the RP2D.
  All patients will be assessed for safety, pharmacokinetics, biomarkers and tumor response.

Eligibility: *Additional cohort specific criteria may apply
  Inclusion Criteria:
  -  Ability to provide written informed consent in accordance with federal, local, and institutional guidelines
  -  Histological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapy
  -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
  -  Life Expectancy of at least 3 months
  -  Adequate hepatic, renal, cardiac, and hematologic function
  -  Measurable disease by RECISTv1.1 criteria
  -  Resolution of treatment-related toxicities
  Exclusion Criteria:
  -  Unable to receive oral medications
  -  Unable to receive oral or IV hydration
  -  Intolerance to prior anti-PD-1/PD-L1 therapy
  -  Prior severe hypersensitivity reaction to another monoclonal antibody (mAb)
  -  Any other current or previous malignancy within 3 years except protocol allowed malignancies
  -  Chemotherapy, Tyrosine Kinase Inhibitor therapy, radiation therapy or hormonal therapy within 2 weeks
  -  Immunotherapy or biological therapy, or investigational agent within 3 weeks (Note: some cohort exceptions allow anti-PD-1 therapy)
  -  Active known or suspected exclusionary autoimmune disease
  -  Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other systemic immunosuppressive medications within 2 weeks
  -  History of known risks factors for bowel perforation
  -  Symptomatic ascites or pleural effusion
  -  Major surgery within 28 days before Cycle 1 Day 1
  -  Active infection requiring within 2 weeks prior to first dose of study drug
  -  Patients who have HIV, Hepatitis B or C
  -  Conditions that could interfere with treatment or protocol-related procedures
  -  Active, non-stable brain metastases or CNS disease
  -  Known deficiencies or suspected defect in the urea cycle

Relevance to patient case: not relevant