A PHASE Ia/b, OPEN-LABEL, DOSE-ESCALATION STUDY OF THE SAFETY AND PHARMACOKINETICS OF RUNIMOTAMAB ADMINISTERED INTRAVENOUSLY AS A SINGLE AGENT AND IN COMBINATION WITH TRASTUZUAMB IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC HER2-EXPRESSING CANCERS
- Conditions
- Breast cancercancer10027656
- Registration Number
- NL-OMON54065
- Lead Sponsor
- Genentech Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 20
General inclusion criteria:
* ECOG Performance Status of 0 or 1
* Life expectancy of at least 12 weeks
* Adequate hematologic and end-organ function
* LVEF equal to or over 50% by either ECHO or MUGA scan
* All acute, clinically significant treatment-related toxicity from prior
therapy, except for alopecia and G2 anemia (Hb 9.0 g/dL), must have resolved to
grade equal to or under 1 prior to study entry
HER2-Positive Breast Cancer-Specific Inclusion Criteria:
* Locally tested, HER2 BC
* Locally advanced or metastatic BC that has relapsed or is refractory to
established therapies
HER2-Positive gastric/gej cancer-specific inclusion criteria:
* Histologically or cytologically documented adenocarcinoma of the stomach or
GEJ with inoperable locally advanced or recurrent and/or metastatic disease,
not amenable to curative therapy.
* HER2 tumor (primary tumor or metastasis) as assessed by local (non-central)
laboratory testing
* Must have received prior trastuzumab, cisplatin (or carboplatin or
oxaliplatin or investigational platinum agent) and 5-FU/capecitabine
For more specific inclusion criteria, please refer to p.104-106 of the protocol
Patients who meet any of the following criteria will be excluded from study
entry. Unless specified, all exclusion criteria listed apply to both the Phase
Ia and Ib:
* Pregnant or breastfeeding, or intending to become pregnant during the study
or within 140 days after the last dose of Runimotamab or tocilizumab, and
within 7 months after the last dose of trastuzumab (for the Phase Ib).
* Significant cardiopulmonary dysfunction
* Known clinically significant liver disease
* Positive serologic or PCR test results for acute or chronic HBV infection
* Acute or chronic HCV infection
* 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 QT
interval
* Primary 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 & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>1. Occurrence, nature, and severity of adverse events graded according to NCI<br /><br>CTCAE v5.0 and the Modified Cytokine Release Syndrome Grading System<br /><br>2. Changes from baseline in LVEF as assessed by ECHO/MUGA scans<br /><br>3. Change from baseline in targeted vital signs<br /><br>4. Change from baseline in targeted clinical laboratory test results, including<br /><br>ECGs<br /><br>5. Number of cycles received and dose intensity<br /><br>6. Occurrence and nature of DLTs</p><br>
- Secondary Outcome Measures
Name Time Method <p>1. Area Under the Serum Concentration vs. Time Curve (AUC) of Runimotamab<br /><br>2. Maximum Observed Serum Concentration (Cmax) of Runimotamab<br /><br>3. Minimum Observed Serum Concentration (Cmin) of Runimotamab<br /><br>4. Clearance (CL)<br /><br>5. Volume of Distribution at Steady State (Vss) of Runimotamab<br /><br>6. Objective response<br /><br>7. Duration of response<br /><br>8. Presence of anti-drug antibodies (ADAs) during the study relative to the<br /><br>presence of ADAs at baseline</p><br>