A Study of Runimotamab in Participants With Locally Advanced or Metastatic HER2-Expressing Cancers

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03448042
• Other study ID #: GO40311
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: June 6, 2018
• Est. completion date: May 31, 2025

Study information

• Verified date: April 2024
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 537
• Est. completion date: May 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Solid Tumors

Intervention

Drug:
• Runimotamab
Runimotamab will be administered via IV infusion until disease progression, intolerable toxicity, or any other discontinuation criteria are met.
• Trastuzumab
Trastuzumab will be administered via IV infusion
• Tocilizumab
Participants will receive IV tocilizumab if needed

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre; Medical Oncology	Melbourne	Victoria
Belgium	Grand Hopital de Charleroi asbl	Charleroi
Canada	Princess Margaret Hospital; Department of Med Oncology	Toronto	Ontario
Denmark	Rigshospitalet	København Ø
France	EDOG - Institut Bergonie - PPDS	Bordeaux
France	Centre Léon Bérard	Lyon
France	Institut Claudius Regaud; Pharmacie	Toulouse
France	Institut Gustave Roussy	Villejuif
Italy	ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda	Milano	Lombardia
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	Istituto Clinico Humanitas	Rozzano (MI)	Lombardia
Japan	National Cancer Center East	Chiba
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Netherlands	Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	Erasmus MC; Afdeling Kindergeneeskunde	Rotterdam
Singapore	National Cancer Centre	Singapore
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Centro Integral Oncológico Clara Campal Ensayos Clínicos START	Madrid
Spain	Fundacion Jimenez Diaz; Servicio de Farmacia	Madrid
Spain	Hospital Universitario Quironsalud Madrid; Servicio de Farmacia	Pozuelo de Alarcón	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Royal Marsden Hospital - Surrey	Surrey
United States	MD Anderson Cancer Center	Houston	Texas
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Washington University; Wash Uni. Sch. Of Med	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  France,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events		From baseline through end of study (approximately 78 months)
Secondary	Serum Concentration of Runimotamab		At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
Secondary	Area Under the Serum Concentration vs. Time Curve (AUC) of Runimotamab		At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
Secondary	Maximum Observed Serum Concentration (Cmax) of Runimotamab		At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
Secondary	Minimum Observed Serum Concentration (Cmin) of Runimotamab		At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
Secondary	Clearance (CL) of Runimotamab		At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
Secondary	Volume of Distribution at Steady State (Vss) of Runimotamab		At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
Secondary	Objective Response (OR) as Determined by the Investigator According to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1)		Baseline through the end of study (approximately 78 months)
Secondary	Duration of Response (DOR)		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)
Secondary	Anti-Drug Antibody (ADA) Levels of Runimotamab		At predefined intervals from Cycle 1, Day 1 (approximately 1 year)