This study has been transitioned to CTIS with ID 2023-504491-15-00 check the CTIS register for the current data. • To evaluate the safety and tolerability of Runimotamab when administered as a single agent (Phase Ia) and in combination with…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Occurrence, nature, and severity of adverse events graded according to NCI
CTCAE v5.0 and the Modified Cytokine Release Syndrome Grading System
2. Changes from baseline in LVEF as assessed by ECHO/MUGA scans
3. Change from baseline in targeted vital signs
4. Change from baseline in targeted clinical laboratory test results, including
ECGs
5. Number of cycles received and dose intensity
6. Occurrence and nature of DLTs
Secondary outcome
1. Area Under the Serum Concentration vs. Time Curve (AUC) of Runimotamab
2. Maximum Observed Serum Concentration (Cmax) of Runimotamab
3. Minimum Observed Serum Concentration (Cmin) of Runimotamab
4. Clearance (CL)
5. Volume of Distribution at Steady State (Vss) of Runimotamab
6. Objective response
7. Duration of response
8. Presence of anti-drug antibodies (ADAs) during the study relative to the
presence of ADAs at baseline
Background summary
Locally advanced and metastatic HER2-positive breast and gastric cancers
largely remain incurable diseases, with most patients progressing after
receiving HER2-targeted therapies. T cell-recruiting bispecific agents
represent an alternative mechanism to induce T cell-mediated killing of
HER2-expressing cancer cells. While there are limited clinical data with these
agents in HER2-expressing cancers to date, these agents have shown evidence of
clinical activity in hematologic malignancies, as exemplified by clinical
activity observed with the CD19-directed bispecific molecule blinatumomab in
both B-cell acute lymphoblastic leukemia (ALL; Blincyto USPI) and non-Hodgkin
lymphoma (NHL; Topp et al. 2015; Viardot et al. 2016).
Although the rationale for molecular-targeted therapies is well established,
the use of anti-HER2 therapies, outside of BC and gastric/GEJ cancer, has been
limited. HER2 overexpression and gene amplification has been described in
several different tumor types, including NSCLC, pancreatic cancer, colorectal
cancer, bladder cancer, salivary duct carcinoma, epithelial ovarian cancer, and
endometrial cancer (Omar et al. 2015; Yan et al. 2015). Currently there are
several ongoing studies investigating HER2-targeted therapies in a broad range
of tumor types (Parakh et al. 2017).
Runimotamab*s novel mechanism of action has the potential to provide clinical
benefit and another therapeutic option for patients with HER2-positive solid
tumors.
Study objective
This study has been transitioned to CTIS with ID 2023-504491-15-00 check the CTIS register for the current data.
• To evaluate the safety and tolerability of Runimotamab when administered as
a single agent (Phase Ia) and in combination with trastuzumab (Phase Ib)
• To determine the maximum tolerated dose (MTD), to identify the recommended
phase II dose (RP2D), and to characterize the dose-limiting toxicities (DLTs)
associated with Runimotamab as a single agent (Phase Ia) and in combination
with trastuzumab (Phase Ib)
Study design
This Phase Ia/b, open-label, multicenter, dose-escalation study designed to
evaluate the safety, tolerability, and pharmacokinetics of Runimotamab, to make
a preliminary assessment of antitumor activity of Runimotamab, administered as
a single agent and in combination with trastuzumab, and to identify recommended
Phase II doses (RP2D) for Runimotamab as a single agent and in combination with
trastuzumab in patients with locally advanced or metastatic HER2-expressing
cancers for which standard therapy does not exist, has proven to be ineffective
or intolerable, or is considered inappropriate.
Patients will be enrolled in two stages: a dose-escalation stage (Phase Ia/b)
and a dose-expansion stage. The safety, pharmacokinetics,
pharmacodynamics, and preliminary anti-tumor activity data in the Phase Ia and
Ib dose escalation stages will be evaluated, in order to select the dose(s) and
schedule(s) for the planned expansion stages (Runimotamab as a single agent
and/or in combination with trastuzumab). Approximately 213-521 patients may be
enrolled in this global study, at approximately 35 investigative sites.
Intervention
- Intravenous infusion of Runimotamab
- Intravenous infusion of trastuzumab (in phase 1b only)
- Intravenous infusion of tocilizumab (in patients experiencing Cytokine
release syndrome as a side-effect)
Study burden and risks
This is a phase 1 first in human study of Runimotamab as a single agent and in
combination with Trastuzumab for people with HER2 positive breast cancer and
gastro-esophageal junction cancer. Approximately 231-521 participants are
enrolled in either a dose-escalation or dose-expansion stage to assess the
safety, tolerability and preliminary efficacy of the study drug. Patients will
undergo tumor assessments, physical examinations, pregnancy tests, blood draws
for laboratory analysis, liver function tests, scans and biopsies (both
mandatory and optional).
DNA Way 1
South San Fransisco, CA 94080-4990
US
DNA Way 1
South San Fransisco, CA 94080-4990
US
Listed location countries
Age
Inclusion criteria
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
Exclusion criteria
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-504491-15-00 |
| EudraCT | EUCTR2019-004596-39-NL |
| ClinicalTrials.gov | NCT03448042 |
| CCMO | NL76482.056.21 |