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

Roche

Status and phase: Enrolling; Phase 1

Conditions: Small Cell Lung Cancer; Neuroendocrine Carcinoma

Treatments: Drug: Tocilizumab; Drug: RO7616789

Study type: Interventional

Funder types: Industry

Identifiers

NCT05619744

BP44382

2023-506354-20-00 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 168 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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168 participants in 3 patient groups

Part 1: RO7616789 QW: Dose Escalation

Experimental group

Description:

Participants will receive a fixed dose of RO7616789 intravenously once weekly (QW) per dose level on Day 1, 8, and 15 of each 21-day cycle. In case of toxicity, step-up (single or double) dosing may be explored.

Treatment:

Drug: RO7616789

Drug: Tocilizumab

Part 2: RO7616789 Q3W: Dose Escalation

Experimental group

Description:

Participants will receive a fixed dose of RO7616789, at a dose determined in Part 1, intravenously once every 3 weeks (Q3W) on Day 1 of each 21-day cycle. In case of toxicity, step-up (single or double) dosing may be explored.

Treatment:

Drug: RO7616789

Drug: Tocilizumab

Part 3: Dose Expansion

Experimental group

Description:

Based on emerging data from Part 1 and 2, one or more dosing regimens will be further investigated in Part 3.

Treatment:

Drug: RO7616789

Drug: Tocilizumab