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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: Runimotamab
* Drug: Trastuzumab
* Drug: Tocilizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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) |