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 CancerNeuroendocrine Carcinoma
- Interventions
- Registration Number
- NCT05619744
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 41
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 3: Dose Expansion RO7616789 Based on emerging data from Part 1 and 2, one or more dosing regimens will be further investigated in Part 3. Part 2: RO7616789 Q3W: Dose Escalation RO7616789 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. Part 3: Dose Expansion Tocilizumab Based on emerging data from Part 1 and 2, one or more dosing regimens will be further investigated in Part 3. Part 1: RO7616789 QW: Dose Escalation RO7616789 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. Part 1: RO7616789 QW: Dose Escalation Tocilizumab 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. Part 2: RO7616789 Q3W: Dose Escalation Tocilizumab 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.
- Primary Outcome Measures
Name Time Method Part 3: Objective Response Rate (ORR) as determined by Investigator Up to approximately 26 months Part 3: Overall Survival (OS) 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: Disease Control Rates 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 1, 2 and 3: Number of Participants with Adverse Events and Serious Adverse Events Up to approximately 26 months 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.
Part 3: Duration of Response (DOR) as Determined by the Investigator Up to approximately 26 months
- Secondary Outcome Measures
Name Time Method Part 1, 2 and 3: Time to Reach Steady State Concentration of RO7616789 Up to approximately 26 months 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 Part 1, 2 and 3: Volume of Distribution of RO7616789 Up to approximately 26 months Part 1, 2 and 3: Accumulation Ratio of RO7616789 Up to approximately 26 months Part 1 and 2: ORR as Determined by the Investigators Up to approximately 26 months Part 1 and 2: DOR as Determined by the Investigators Up to approximately 26 months Part 1, 2 and 3: Percentage of Participants With Anti-Drug Antibody (ADA) to RO7616789 Up to approximately 26 months Part 1 and 2: Disease Control Rates as Determined by the Investigator Up to approximately 26 months Part 1 and 2: PFS as Determined by the Investigators Up to approximately 26 months Part 1 and 2: OS as Determined by the Investigators Up to approximately 26 months
Trial Locations
- Locations (17)
Georgetown Uni Medical Center
🇺🇸Washington, District of Columbia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
The Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Rigshospitalet
🇩🇰København Ø, Denmark
Uniwersyteckie Centrum Kliniczne
🇵🇱Gda?sk, Poland
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain