Clinical trial NCT05619744: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Small Cell Lung Cancer
Neuroendocrine Carcinoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-11-17
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Part 1, 2 and 3: Number of Participants with Adverse Events and Serious Adverse Events
timeFrame: Up to approximately 26 months
measure: Part 1 and 2: Number of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 through Day 21 in cycle 1 (Cycle is 21 days)
measure: Part 3: Objective Response Rate (ORR) as determined by Investigator
timeFrame: Up to approximately 26 months
measure: Part 3: Disease Control Rates as Determined by the Investigator
timeFrame: Up to approximately 26 months
measure: Part 3: Duration of Response (DOR) as Determined by the Investigator
timeFrame: Up to approximately 26 months
measure: Part 3: Progression Free Survival (PFS) as Determined by the Investigator
timeFrame: Up to approximately 26 months
measure: Part 3: Overall Survival (OS)
timeFrame: Up to approximately 26 months
Secondary outcomes:
measure: Part 1, 2 and 3: Serum Concentration of RO7616789
timeFrame: Up to approximately 26 months
measure: Part 1, 2 and 3: Maximum Serum Concentration (Cmax) of RO7616789
timeFrame: Up to approximately 26 months
measure: Part 1, 2 and 3: Area Under the Concentration-Time Curve (AUC) of RO7616789
timeFrame: Up to approximately 26 months
measure: Part 1, 2 and 3: Total Clearance of RO7616789
timeFrame: Up to approximately 26 months
measure: Part 1, 2 and 3: Terminal Half-Life of RO7616789
timeFrame: Up to approximately 26 months
measure: Part 1, 2 and 3: Volume of Distribution of RO7616789
timeFrame: Up to approximately 26 months
measure: Part 1, 2 and 3: Time to Reach Steady State Concentration of RO7616789
timeFrame: Up to approximately 26 months
measure: Part 1, 2 and 3: Accumulation Ratio of RO7616789
timeFrame: Up to approximately 26 months
measure: Part 1 and 2: ORR as Determined by the Investigators
timeFrame: Up to approximately 26 months
measure: Part 1 and 2: Disease Control Rates as Determined by the Investigator
timeFrame: Up to approximately 26 months
measure: Part 1 and 2: DOR as Determined by the Investigators
timeFrame: Up to approximately 26 months
measure: Part 1 and 2: PFS as Determined by the Investigators
timeFrame: Up to approximately 26 months
measure: Part 1 and 2: OS as Determined by the Investigators
timeFrame: Up to approximately 26 months
measure: Part 1, 2 and 3: Percentage of Participants With Anti-Drug Antibody (ADA) to RO7616789
timeFrame: Up to approximately 26 months
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown Uni Medical Center
state: District of Columbia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: København Ø
country: Denmark
facility: Rigshospitalet
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Gda?sk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: