Phase 1 Dose Escalation Trial of ZM008, an Anti-LLT1 Antibody, as Single Agent Followed by Combination With Pembrolizumab in Patients With Advanced Solid Tumors
This is a phase 1 dose escalation trial of ZM008, an anti-LLT1 antibody as a single agent followed by combination with Pembrolizumab in patients with advanced solid tumors who have exhausted all standard therapy available or are intolerant of the same.
• Age greater than 18 years at the time of signing the informed consent form.
• Patients with histologically confirmed diagnosis of locally advanced, locoregionally recurrent, not amenable to curative therapy, or metastatic solid tumors that have no standard therapeutic option or are intolerant to the therapies. Tumor types to be included are Non Small Cell Lung Cancer, Triple Negative Breast Cancer, Head \& Neck Squamous Cell Cancer, Prostate Cancer, Colorectal cancer, pancreatic ductal adenocarcinoma, biliary tract cancer, high grade serous ovarian cancer, diffuse large B-cell lymphoma or Urothelial Cancer.
• Patients with tumors with actionable mutations should have progressed on all approved targeted therapies or have them contraindicated.
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 on computed tomography (CT), positron emission tomography (PET)/CT or magnetic resonance imaging (MRI) scan.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
• The patient has adequate hematologic function as defined by:
‣ Hemoglobin ≥9 g/dL (whole or partial blood transfusions not allowed in the weeks).
⁃ Absolute neutrophil count ≥1.0 × 109/L (growth factors like granulocyte colony- stimulating factors are not allowed in the two previous weeks).
⁃ Platelet count ≥75 × 109/L (platelet transfusions are not allowed in the 2 previous weeks).
• The patient has adequate hepatic function as defined by:
‣ Total bilirubin ≤1.5 times upper limit of normal (ULN).
⁃ AST and ALT ≤3.0 times ULN, (if liver metastases are present, then ≤5.0 times ULN is allowed).
• The patient has adequate renal function as defined by:
• • Estimated creatinine clearance (CrCL) using the Cockcroft-Gault formula
• ≥30 mL/minute. Patients with calculated CrCL \<30 mL/minute can be enrolled if measured CrCL is ≥30 mL/minute.
• Women of childbearing potential (WOCBP) and men with sexual partners who are WOCBP must consent to adhere to contraceptive requirements from the day of the signature of the informed consent to at least 4 months after the last dose of trial treatment.
⁃ Suitable venous access for safe drug administration and the trial-required drug concentration and pharmacodynamic sampling.
⁃ Access to archival biopsy if available. If no archival tissue is available, the patient can still be enrolled in the escalation phase but not in the subsequent cohort expansion study. Part 2.