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

Small Cell Lung Cancer Clinical Trial

Official title:

An Open-Label, Multicenter Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of RO7616789 in Participants With Advanced Small Cell Lung Cancer and Other Neuroendocrine Carcinomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05619744
• Other study ID #: BP44382
• Secondary ID: 2023-506354-20-0
• Status: Recruiting
• Phase: Phase 1
• Start date: January 23, 2023
• Est. completion date: September 30, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BP44382 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 168
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Neuroendocrine
• Lung Neoplasms
• Neuroendocrine Carcinoma
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• RO7616789
RO7616789 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective part.
• Tocilizumab
Tocilizumab will be used as rescue therapy, in case of clinical presentation of cytokine release syndrome (CRS). Tocilizumab solution for infusion will be administered intravenously at 8 mg/kg for participants >/= 30 kg or at 12 mg/kg for participants < 30 kg.

Locations

Country	Name	City	State
Denmark	Rigshospitalet; Fase 1 Enhed - Onkologi	København Ø
Japan	National Cancer Center Hospital East; Thoracic Oncology	Chiba
Japan	National Cancer Center Hospital	Tokyo
Poland	Uniwersyteckie Centrum Kliniczne; Osrodek Badan Wczesnych Faz	Gda?sk
Spain	Hospital Universitari Vall d'Hebron; Oncology	Barcelona
Spain	Fundacion Jimenez Diaz; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
United States	Massachusetts General Hospital;Oncology	Boston	Massachusetts
United States	The Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Henry Ford Hospital; Josephine Ford Cancer Center	Detroit	Michigan
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pittsburgh Medical Center; Division of Hematology-Oncology	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Georgetown Uni Medical Center; Lombardi Cancer Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Denmark,  Japan,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1, 2 and 3: Number of Participants with Adverse Events and Serious Adverse Events	Adverse events were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), and Cytokine release syndrome (CRS), will be graded based on the American Society for Transplantation and Cell Therapy (ASTCT) criteria.	Up to approximately 26 months
Primary	Part 1 and 2: Number of Participants with Dose Limiting Toxicities (DLTs)		Day 1 through Day 21 in cycle 1 (Cycle is 21 days)
Primary	Part 3: Objective Response Rate (ORR) as determined by Investigator		Up to approximately 26 months
Primary	Part 3: Disease Control Rates as Determined by the Investigator		Up to approximately 26 months
Primary	Part 3: Duration of Response (DOR) as Determined by the Investigator		Up to approximately 26 months
Primary	Part 3: Progression Free Survival (PFS) as Determined by the Investigator		Up to approximately 26 months
Primary	Part 3: Overall Survival (OS)		Up to approximately 26 months
Secondary	Part 1, 2 and 3: Serum Concentration of RO7616789		Up to approximately 26 months
Secondary	Part 1, 2 and 3: Maximum Serum Concentration (Cmax) of RO7616789		Up to approximately 26 months
Secondary	Part 1, 2 and 3: Area Under the Concentration-Time Curve (AUC) of RO7616789		Up to approximately 26 months
Secondary	Part 1, 2 and 3: Total Clearance of RO7616789		Up to approximately 26 months
Secondary	Part 1, 2 and 3: Terminal Half-Life of RO7616789		Up to approximately 26 months
Secondary	Part 1, 2 and 3: Volume of Distribution of RO7616789		Up to approximately 26 months
Secondary	Part 1, 2 and 3: Time to Reach Steady State Concentration of RO7616789		Up to approximately 26 months
Secondary	Part 1, 2 and 3: Accumulation Ratio of RO7616789		Up to approximately 26 months
Secondary	Part 1 and 2: ORR as Determined by the Investigators		Up to approximately 26 months
Secondary	Part 1 and 2: Disease Control Rates as Determined by the Investigator		Up to approximately 26 months
Secondary	Part 1 and 2: DOR as Determined by the Investigators		Up to approximately 26 months
Secondary	Part 1 and 2: PFS as Determined by the Investigators		Up to approximately 26 months
Secondary	Part 1 and 2: OS as Determined by the Investigators		Up to approximately 26 months
Secondary	Part 1, 2 and 3: Percentage of Participants With Anti-Drug Antibody (ADA) to RO7616789		Up to approximately 26 months