- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02906670
Sym013 (Pan-HER) in Patients With Advanced Epithelial Malignancies
An Open-label, Multicenter, Phase 1a/2a Trial Investigating the Safety, Tolerability and Antitumor Activity of Multiple Doses of Sym013, a mAb Mixture Targeting EGFR, HER2 and HER3, in Patients With Advanced Epithelial Malignancies
Study Overview
Detailed Description
This is an open-label, multicenter trial composed of 2 parts in which Sym013 will be evaluated when administered by intravenous infusion in patients with advanced epithelial malignancies without available therapeutic options.
Part 1 is a Phase 1a dose-escalation evaluating weekly (Q1W) and every second week (Q2W) schedules of administration in separate dose-escalation cohorts to determine the recommended phase 2 dose (RP2D) and regimen of Sym013.
Part 2 is a Phase 2a dose-expansion at the RP2D and regimen. Four (4) dose-expansion cohorts will be evaluated in this part of the trial and will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets. Patients will be entered, depending upon either a defined molecular profile or profiles, or their underlying malignancy, to 1 of 4 corresponding expansion cohorts: Cohort A, Cohort B, Cohort C, or Cohort D.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
-
-
Texas
-
San Antonio, Texas, United States, 78229
- South Texas Accelerated Research Therapeutics, LLC
-
San Antonio, Texas, United States, 78240
- NEXT Oncology
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Main inclusion criteria all patients, Part 1 and Part 2:
- Male or female, at least 18 years of age at the time of informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Life expectancy >3 months assessed during Screening
- Documented (histologically- or cytologically-proven) epithelial malignancy that is locally advanced or metastatic, having received all therapy known to confer clinical benefit
Additional inclusion criteria applicable to Part 2 ONLY:
- Epithelial malignancy (tumor types to be determined), measurable according to RECIST v1.1 that has been confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) within 4 weeks prior to C1/D1
- Willingness to undergo a pre-and post-dosing biopsy (total of 2 biopsies) from primary or metastatic tumor site(s) considered safe for biopsy
Exclusion Criteria:
- Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks or 5 plasma half-lives (whichever is shortest) prior to C1/D1, except nitrosoureas and mitomycin C within 6 weeks prior to C1/D1.
- Part 2 ONLY: Radiotherapy against target lesions within 4 weeks prior to C1/D1, unless there is documented progression of the lesion following radiotherapy
- Immunosuppressive or systemic hormonal therapy (>10 mg daily prednisone equivalent) within 2 weeks prior to C1/D1 with exceptions
- Use of hematopoietic growth factors within 2 weeks prior to C1/D1
- Active second malignancy or history of another malignancy within the last 3 years, with allowed exceptions
Central nervous system (CNS) malignancies including:
- Primary malignancies of the CNS
- Known, untreated CNS or leptomeningeal metastases, or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS metastatic involvement for which treatment is required
- Inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy
- Major surgical procedure within 4 weeks prior to C1/D1 or inadequate recovery from any prior surgical procedure
- Non-healing wounds on any part of the body
- Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks prior to C1/D1, unless adequately treated and stable
- Active uncontrolled bleeding or a known bleeding diathesis
- Significant gastrointestinal abnormalities
- Significant cardiovascular disease or condition
- Abnormal hematologic, renal or hepatic function
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 1 mg/kg Q1W
Phase 1a: Patients are administered a weekly dose of 1 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.
|
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: 2 mg/kg Q1W
Phase 1a: Patients are administered a weekly dose of 2 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.
|
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: 4 mg/kg Q1W
Phase 1a: Patients are administered a weekly dose of 4 mg/kg of Sym013 until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.
|
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: 6 mg/kg Q1W + Prophylaxis
Phase 1a: Patients are administered a weekly dose of 6 mg/kg of Sym013 + premedication until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw. Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen. |
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: 9 mg/kg Q1W + Prophylaxis
Phase 1a: Patients are administered a weekly dose of 9 mg/kg of Sym013 + premedication until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw. Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen. |
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: 6 mg/kg Q2W
Phase 1a: Patients are administered a dose of 6 mg/kg of Sym013 every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.
|
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: 9 mg/kg Q2W
Phase 1a: Patients are administered a dose of 9 mg/kg of Sym013 every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw.
|
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: 9 mg/kg Q2W + Prophylaxis
Phase 1a: Patients are administered a dose of 9 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw. Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen. |
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: 12 mg/kg Q2W + Prophylaxis
Phase 1a: Patients are administered a dose of 12 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw. Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen. |
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: 15 mg/kg Q2W + Prophylaxis
Phase 1a: Patients are administered a dose of 15 mg/kg of Sym013 + premedication every second week until unacceptable toxicity, progressive disease, termination of the trial or patient decision to withdraw. Premedications for infusion-related reactions included glucocorticoids and an antihistamine (H1 antagonist) prior to each dose of Pan-HER from the beginning of the study. As of Protocol Amendment 5, additional premedications were added which included montelukast, dexamethasone, antihistamine (H2 antagonist), and acetaminophen. |
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: Phase 2a Dose-Expansion Cohort A
Part 2 is a Phase 2a dose-expansion with Sym013 at the RP2D and regimen.
One (1) of 4 tumor types to be evaluated in this arm of the trial will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets.
|
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: Phase 2a Dose-Expansion Cohort B
Part 2 is a Phase 2a dose-expansion with Sym013 at the RP2D and regimen.
One (1) of 4 tumor types to be evaluated in this arm of the trial will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets.
|
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: Phase 2a Dose-Expansion Cohort C
Part 2 is a Phase 2a dose-expansion with Sym013 at the RP2D and regimen.
One (1) of 4 tumor types to be evaluated in this arm of the trial will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets.
|
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
EXPERIMENTAL: Phase 2a Dose-Expansion Cohort D
Part 2 is a Phase 2a dose-expansion with Sym013 at the RP2D and regimen.
One (1) of 4 tumor types to be evaluated in this arm of the trial will be selected based upon findings from Part 1, additional preclinical data, and additional clinical data available at that time from other agents inhibiting these targets.
|
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes or domains on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Part 1: Assess the Safety and Tolerability of Sym013 When Administered Either Q1W or Q2W to Separate Dose-escalation Cohorts of Patients.
Time Frame: 24 months
|
Assess the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym013 administration.
|
24 months
|
Part 2: Evaluate the Antitumor Effect of Sym013 When Administered at the RP2D and Regimen to Patients.
Time Frame: 24 months
|
No data were collected for this Outcome Measures as Part 2 of the trial was never initiated.
|
24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Part 1: Determine the RP2D and Regimen of Sym013.
Time Frame: 24 months
|
No RP2D or regimen of Sym013 was determined as the trial was prematurely terminated
|
24 months
|
Parts 1 and 2: Evaluate the Immunogenicity of Sym013.
Time Frame: 42 months
|
Serum sampling to assess the potential for anti-drug antibody (ADA) formation was not analyzed as the trial was prematurely terminated
|
42 months
|
Parts 1 and 2: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC).
Time Frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
|
Will be estimated using non-compartmental methods and actual time points.
|
0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
|
Parts 1 and 2: Maximum Concentration (Cmax) and Trough Concentration (Ctrough) - Mean Values.
Time Frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
|
Will be derived from observed data.
|
0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
|
Parts 1 and 2: Time to Reach Maximum Concentration (Tmax).
Time Frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
|
Will be derived from observed data.
End of infusion was defined as time zero (0)
|
0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
|
Parts 1 and 2: Elimination Half-life (T½).
Time Frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
|
Will be estimated using non-compartmental methods and actual time points
|
0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
|
Parts 1 and 2: Clearance (CL).
Time Frame: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
|
Will be estimated using non-compartmental methods and actual time points.
|
0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jordan Berlin, MD, Vanderbilt University Medical Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Sym013-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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