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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Runimotamab; Drug: Trastuzumab; Drug: Tocilizumab

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
• Belgium
  • Charleroi, Belgium, 6000
    • Grand Hopital de Charleroi asbl
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet-Blegdamsvej 9
• France
  • Toulouse, France, 31059
    • Institut Claudius Regaud
  • Gironde
    • Bordeaux, Gironde, France, 33000
      • EDOG - Institut Bergonie - PPDS
  • Rhône
    • Lyon, Rhône, France, 69008
      • Centre Leon Berard
  • Val-de-Marne
    • Villejuif, Val-de-Marne, France, 94805
      • Gustave Roussy
• Italy
  • Lombardy
    • Milan, Lombardy, Italy, 20162
      • ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
• Japan
  • Chiba, Japan, 277-8577
    • National Cancer Center East
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
• Singapore
  • Singapore, Singapore, 168583
    • National Cancer Centre
• South Korea
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 110-744
    • Seoul National University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28040
    • START MADRID_Hospital Universiario Fundacion Jimenez Diaz
  • Madrid, Spain, 28050
    • START MADRID_Hospital Universitario HM Sanchinarro - CIOCC - EDOS
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quironsalud Madrid
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital
• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LJ
      • Churchill Hospital
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Michigan
    • Saint Louis, Michigan, United States, 63130
      • Washington University
  • New York
    • New York, New York, United States, 10017
      • Memorial Sloan Kettering Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Participants will be assigned sequentially to escalating doses of runimotamab up to the maximum tolerated dose (MTD).	Drug: Runimotamab; Runimotamab will be administered via IV infusion until disease progression, intolerable toxicity, or any other discontinuation criteria are met.; Other Names: BTRC4017A; RO7227780; Drug: Trastuzumab; Trastuzumab will be administered via IV infusion; Drug: Tocilizumab; Participants will receive IV tocilizumab if needed
Experimental: Dose Expansion; Participants will receive runimotamab based on the MTD or maximum allowed dose (MAD) identified during dose escalation.	Drug: Runimotamab; Runimotamab will be administered via IV infusion until disease progression, intolerable toxicity, or any other discontinuation criteria are met.; Other Names: BTRC4017A; RO7227780; Drug: Trastuzumab; Trastuzumab will be administered via IV infusion; Drug: Tocilizumab; Participants will receive IV tocilizumab if needed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Adverse Events	From baseline through end of study (approximately 78 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum Concentration of Runimotamab	At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
Area Under the Serum Concentration vs. Time Curve (AUC) of Runimotamab	At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
Maximum Observed Serum Concentration (Cmax) of Runimotamab	At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
Minimum Observed Serum Concentration (Cmin) of Runimotamab	At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
Clearance (CL) of Runimotamab	At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
Volume of Distribution at Steady State (Vss) of Runimotamab	At predefined intervals from Cycle 1, Day 1 (approximately 1 year)
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)
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)
Anti-Drug Antibody (ADA) Levels of Runimotamab	At predefined intervals from Cycle 1, Day 1 (approximately 1 year)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2018
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: February 20, 2018
• First Submitted That Met QC Criteria: February 26, 2018
• First Posted (Actual): February 27, 2018

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Trastuzumab; tocilizumab
• Other Study ID Numbers: GO40311

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No