a study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of ro7616789 in advanced small cell lung cancer and other neuroendocrine carcinomas

Conditions: Small Cell Lung Cancer; Neuroendocrine Carcinoma

Summary: the purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (pk), pharmacodynamics (pd) and preliminary anti-tumor activity of ro7616789. the study will have 3 parts: dose escalation (parts 1 and 2) and dose expansion (part 3). participants with advanced stage small cell lung cancer (sclc) and neuroendocrine carcinoma (nec) will be enrolled in the study.


Eligibility criteria:
inclusion criteria: * life expectancy at least 12 weeks * eastern cooperative oncology group (ecog) performance status of 0 or 1 * adequate hematologic and end organ function * negative serum pregnancy test. * adequate contraception and no or interruption of breastfeeding * histologically confirmed extensive sclc or poorly differentiated nec of any other origin, relapsed after at least 1 systemic therapy * measurable disease according to response evaluation criteria in solid tumors (recist) version 1.1 * confirmed availability of representative archival tumor specimens in formalin-fixed, paraffin-embedded (ffpe) blocks or unstained slides exclusion criteria: * pregnant or breastfeeding, or intending to become pregnant during the study or within 40 days after the final dose of study treatment * poorly controlled type 2 diabetes mellitus defined as a screening hemoglobin a1c ≥ 8% or a fasting plasma glucose ≥ 160 mg/dl (or 8.8 mmol/l) * qt interval corrected using fridericia's formula (qtcf) \> 470 ms. abnormal electrocardiograms (ecgs) (triplicate) should be performed \> 30 minutes apart * current treatment with medications that are well known to prolong the qt interval * prior treatment with anti-cluster of differentiation (cd)137 agents, anti-cd3 agents and/or delta-like ligand 3 (dll3) targeted therapies * any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, or radiotherapy, within 21 days prior to initiation of study treatment * any history of an immune-related grade 4 adverse event (ae) attributed to prior anti-programmed death ligand-1 (pd-l1) /pd-1 or anti-cytotoxic t-lymphocyte-associated protein (ctla-4) therapy (other than asymptomatic elevation of serum amylase or lipase) * any history of an immune-related grade 3 adverse event attributed to prior anti-pd-l1 /pd-1 or anti-ctla-4 therapy (other than asymptomatic elevation of serum amylase or lipase) that resulted in permanent discontinuation of the prior immunotherapeutic agent * history or clinical evidence of primary central nervous system (cns) malignancy, symptomatic cns metastases, cns metastases requiring any anti-tumor treatment, or leptomeningeal disease and current or history of cns disease, such as stroke, epilepsy, cns vasculitis, or neurodegenerative disease * spinal cord compression that has not been definitively treated with surgery and/or radiation * active or history of clinically significant autoimmune disease * positive test for human immunodeficiency virus (hiv) infection * positive hepatitis b surface antigen (hbsag) test, and/or positive total hepatitis b core antibody (hbcab) test at screening * prior allogeneic hematopoietic stem cell transplantation or prior solid organ transplantation * administration of a live, attenuated vaccine within 4 weeks before first ro7616789 infusion * known allergy or hypersensitivity to any component of the ro7616789 formulation