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

• ClinicalTrials.gov Identifier: NCT03448042
• Recruitment Status: Recruiting
• First Posted: February 27, 2018
• Last Update Posted: May 19, 2023
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: February 20, 2018
• First Posted Date: February 27, 2018
• Last Update Posted Date: May 19, 2023
• Actual Study Start Date: June 6, 2018
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 26, 2018): Percentage of Participants with Adverse Events [ Time Frame: From baseline through end of study (approximately 78 months) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 25, 2022)

• Serum Concentration of Runimotamab [ Time Frame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year) ]
• Area Under the Serum Concentration vs. Time Curve (AUC) of Runimotamab [ Time Frame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year) ]
• Maximum Observed Serum Concentration (Cmax) of Runimotamab [ Time Frame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year) ]
• Minimum Observed Serum Concentration (Cmin) of Runimotamab [ Time Frame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year) ]
• Clearance (CL) of Runimotamab [ Time Frame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year) ]
• Volume of Distribution at Steady State (Vss) of Runimotamab [ Time Frame: 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) [ Time Frame: Baseline through the end of study (approximately 78 months) ]
• Duration of Response (DOR) [ Time Frame: 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 [ Time Frame: At predefined intervals from Cycle 1, Day 1 (approximately 1 year) ]

Original Secondary Outcome Measures (submitted: February 26, 2018)

• Serum Concentration of BTRC4017A [ Time Frame: At predefined intervals from Cycle 1, Day 1, up to approximately 1 year. ]
• Area Under the Serum Concentration vs. Time Curve (AUC) of BTRC4017A [ Time Frame: At predefined intervals from Cycle 1, Day 1, up to approximately 1 year. ]
• Maximum Observed Serum Concentration (Cmax) of BTRC4017A [ Time Frame: At predefined intervals from Cycle 1, Day 1, up to approximately 1 year. ]
• Minimum Observed Serum Concentration (Cmin) of BTRC4017A [ Time Frame: At predefined intervals from Cycle 1, Day 1, up to approximately 1 year. ]
• Clearance (CL) of BTRC4017A [ Time Frame: At predefined intervals from Cycle 1, Day 1, up to approximately 1 year. ]
• Volume of Distribution at Steady State (Vss) of BTRC4017A [ Time Frame: At predefined intervals from Cycle 1, Day 1, up to approximately 1 year. ]
• Objective Response (OR) as Determined by the Investigator According to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1) [ Time Frame: Baseline through the end of study (approximately 78 months) ]
• Duration of Response (DOR) [ Time Frame: From the first occurrence of a documented objective response to first documented disease progression or death from any cause, through the end of study (approximately 78 months) ]
• Anti-Drug Antibody (ADA) Levels of BTRC4017A [ Time Frame: At predefined intervals from Cycle 1, Day 1, up to approximately 1 year. ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumors

Intervention

• 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

Study Arms

• Experimental: Dose Escalation
  Participants will be assigned sequentially to escalating doses of runimotamab up to the maximum tolerated dose (MTD).
  Interventions:

  • Drug: Runimotamab
  • Drug: Trastuzumab
  • Drug: Tocilizumab
• Experimental: Dose Expansion
  Participants will receive runimotamab based on the MTD or maximum allowed dose (MAD) identified during dose escalation.
  Interventions:

  • Drug: Runimotamab
  • Drug: Trastuzumab
  • Drug: Tocilizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 10, 2022): 537
• Original Estimated Enrollment (submitted: February 26, 2018): 449
• Estimated Study Completion Date: April 30, 2024
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: GO40311 https://forpatients.roche.com/; 888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

• Listed Location Countries: Australia, Belgium, Canada, Denmark, France, Italy, Japan, Korea, Republic of, Netherlands, Singapore, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT03448042
• Other Study ID Numbers: GO40311
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Genentech, Inc.

• PRS Account: Genentech, Inc.
• Verification Date: May 2023