Clinical trial NCT03448042: A Study of Runimotamab in Participants With Locally Advanced or Metastatic HER2-Expressing Cancers
Official title: A Phase Ia/Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of Runimotamab Administered Intravenously as a Single Agent and in Combination With Trastuzumab in Patients With Locally Advanced or Metastatic HER2-Expressing Cancers
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2018-02-27
Enrollment: 123
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: This study will evaluate the safety, tolerability, and pharmacokinetics of Runimotamab administered intravenously as a single agent and in combination with Trastuzumab in participants with locally advanced or metastatic Human Epidermal Growth Factor Receptor 2 (HER2)-expressing cancers.


Eligibility criteria: Inclusion Criteria

* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Life expectancy of at least 12 weeks
* Adequate hematologic and end-organ function
* Acute, clinically significant treatment-related toxicity from prior therapy must have resolved to Grade \</=1 prior to study entry
* Left Ventricular Ejection Fraction (LVEF) \>/=50%

HER2-Expressing Breast Cancer-Specific Inclusion Criteria

* Locally tested, Human Epidermal Growth Factor Receptor 2 (HER2)-expressing BC
* Locally advanced or metastatic BC that has relapsed or is refractory to established therapies

HER2-Expressing Gastric/Gastroesophageal (GEJ) Cancer-Specific Inclusion Criteria

* Adenocarcinoma of the stomach or GEJ with inoperable locally advanced or recurrent and/or metastatic disease, not amenable to curative therapy
* HER2-expressing tumor (primary tumor or metastasis) as assessed by local lab testing
* HER2-positive gastric/GEJ cancer must have received prior trastuzumab, cisplatin (or carboplatin or oxaliplatin or investigational platinum agent) and 5-fluorouracil (5-FU)/capecitabine

HER2-Positive Solid Tumor Specific Inclusion Criteria

* HER2-positive tumor (primary tumor or metastasis) as assessed by local (non-central) laboratory testing
* Locally advanced, recurrent, or metastatic incurable malignancy that has progressed after at least one available standard therapy; or for whom standard therapy has proven to be ineffective or intolerable, or is considered inappropriate; or for whom a clinical trial of an investigational agent is a recognized standard of care; or for whom a clinical trial of an investigational agent is considered an acceptable treatment option

Exclusion Criteria

* Pregnant or breastfeeding, or intending to become pregnant during the study or within 140 days after the last dose of runimotamab
* Significant cardiopulmonary dysfunction
* Known clinically significant liver disease
* Positive for acute or chronic Hepatitis B virus (HBV) infection
* Acute or chronic Hepatitis C virus (HCV) infection
* Human Immunodeficiency Virus (HIV) seropositivity
* Poorly controlled Type 2 diabetes mellitus
* History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
* Current treatment with medications that are well known to prolong the Q-wave/T-wave (QT) interval
* Known clinically significant liver disease
* Primary central nervous system (CNS) malignancy, untreated CNS metastases, or active CNS metastases (progressing or requiring corticosteroids for symptomatic control)
* Leptomeningeal disease
* Spinal cord compression that has not definitively treated with surgery and/or radiation
* History of autoimmune disease
* Prior allogeneic stem cell or solid organ transplantation

Primary outcomes:
measure: Percentage of Participants with Adverse Events
timeFrame: From baseline through end of study (approximately 78 months)
Secondary outcomes:
measure: Serum Concentration of Runimotamab
timeFrame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
measure: Area Under the Serum Concentration vs. Time Curve (AUC) of Runimotamab
timeFrame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
measure: Maximum Observed Serum Concentration (Cmax) of Runimotamab
timeFrame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
measure: Minimum Observed Serum Concentration (Cmin) of Runimotamab
timeFrame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
measure: Clearance (CL) of Runimotamab
timeFrame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
measure: Volume of Distribution at Steady State (Vss) of Runimotamab
timeFrame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
measure: Objective Response (OR) as Determined by the Investigator According to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)
timeFrame: Baseline through the end of study (approximately 78 months)
measure: Duration of Response (DOR)
timeFrame: From the first occurrence of a documented objective response to first documented disease progression or death from any cause, through the end of the study (approximately 78 months)
measure: Anti-Drug Antibody (ADA) Levels of Runimotamab
timeFrame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Saint Louis
country: United States
facility: Washington University
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi asbl
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Copenhagen
country: Denmark
facility: Rigshospitalet-Blegdamsvej 9
city: Bordeaux
country: France
facility: EDOG - Institut Bergonie - PPDS
state: Gironde
city: Lyon
country: France
facility: Centre Léon Bérard
state: Rhône
city: Villejuif
country: France
facility: Gustave Roussy
state: Val-de-Marne
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
state: Lombardia
city: Chiba
country: Japan
facility: National Cancer Center East
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Amsterdam
country: Netherlands
facility: Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: START MADRID_Hospital Universiario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: START MADRID_Hospital Universitario HM Sanchinarro - CIOCC - EDOS
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: Oxfordshire
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: