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

NCT05619744 | Completed Phase 1 FDA Drug

• 2 other identifiers: BP443822023-506354-20-00
• Study Type: interventional
• Target: 41
• Locations: 5 countries
• Sites: 17

Brief 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.

Conditions

Small Cell Lung Cancer; Neuroendocrine Carcinoma

Outcome Measures

Primary Outcomes (7)

• 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

• Part 1 and 2: Number of Participants with Dose Limiting Toxicities (DLTs)

  Day 1 through Day 21 in cycle 1 (Cycle is 21 days)

• Part 3: Objective Response Rate (ORR) as determined by Investigator

  Up to approximately 26 months

• Part 3: Disease Control Rates as Determined by the Investigator

  Up to approximately 26 months

• Part 3: Duration of Response (DOR) as Determined by the Investigator

  Up to approximately 26 months

• Part 3: Progression Free Survival (PFS) as Determined by the Investigator

  Up to approximately 26 months

• Part 3: Overall Survival (OS)

  Up to approximately 26 months

Secondary Outcomes (14)

• Part 1, 2 and 3: Serum Concentration of RO7616789

  Up to approximately 26 months

• Part 1, 2 and 3: Maximum Serum Concentration (Cmax) of RO7616789

  Up to approximately 26 months

• Part 1, 2 and 3: Area Under the Concentration-Time Curve (AUC) of RO7616789

  Up to approximately 26 months

• Part 1, 2 and 3: Total Clearance of RO7616789

  Up to approximately 26 months

• Part 1, 2 and 3: Terminal Half-Life of RO7616789

  Up to approximately 26 months

Study Arms (3)

Part 1: RO7616789 QW: Dose Escalation

EXPERIMENTAL

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.

Drug: RO7616789; Drug: Tocilizumab

Part 2: RO7616789 Q3W: Dose Escalation

EXPERIMENTAL

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.

Drug: RO7616789; Drug: Tocilizumab

Part 3: Dose Expansion

EXPERIMENTAL

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

Drug: RO7616789; Drug: Tocilizumab

Interventions

RO7616789 DRUG

RO7616789 solution for infusion will be administered intravenously at a dose and per schedule as specified for the respective part.

Part 1: RO7616789 QW: Dose Escalation; Part 2: RO7616789 Q3W: Dose Escalation; Part 3: Dose Expansion

Tocilizumab DRUG

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.

Also known as: Actemra, RoActemra

Part 1: RO7616789 QW: Dose Escalation; Part 2: RO7616789 Q3W: Dose Escalation; Part 3: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (17)

Georgetown Uni Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202-2689, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Rigshospitalet

København Ø, 2100, Denmark

Location

National Cancer Center Hospital East

Chiba, 277-8577, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214, Poland

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Carcinoma, Neuroendocrine

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: November 17, 2022
• Study Start: January 23, 2023
• Primary Completion: March 4, 2025
• Study Completion: March 4, 2025
• Last Updated: March 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

DK (1); PL (1); US (10); ES (3); JP (2)