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Sym013 (Pan-HER) in Patients With Advanced Epithelial Malignancies

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ClinicalTrials.gov Identifier: NCT02906670
Recruitment Status : Recruiting
First Posted : September 20, 2016
Last Update Posted : July 19, 2018
Sponsor:
Information provided by (Responsible Party):
Symphogen A/S

Brief Summary:
This is the first study to test Sym013 (Pan-HER) in humans. The primary purpose of this study is to see if Sym013 is safe and effective for patients with advanced epithelial malignancies without available therapeutic options.

Condition or disease Intervention/treatment Phase
Oncology Drug: Sym013 Phase 1 Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 134 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 1, 2016
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2020

Arm Intervention/treatment
Experimental: Phase 1a Dose-Escalation (Q1W)
Part 1 is a Phase 1a dose-escalation with Sym013 designed to determine the RP2D and regimen. Patients will receive increasing doses of Sym013 on a Q1W schedule.
Drug: Sym013
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Name: Pan-HER

Experimental: Phase 1a Dose-Escalation (Q2W)
Part 1 is a Phase 1a dose-escalation with Sym013 designed to determine the RP2D and regimen. Patients will receive increasing doses of Sym013 on a Q2W schedule.
Drug: Sym013
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Name: Pan-HER

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.
Drug: Sym013
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Name: Pan-HER

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.
Drug: Sym013
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Name: Pan-HER

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.
Drug: Sym013
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Name: Pan-HER

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.
Drug: Sym013
Sym013 is a recombinant antibody mixture containing 6 humanized immunoglobulin G1 (IgG1) monoclonal antibodies (mAbs), which bind specifically to non-overlapping epitopes on the epidermal growth factor receptor (EGFR), and the human epidermal growth factor receptors (HER) HER2 and HER3.
Other Name: Pan-HER




Primary Outcome Measures :
  1. 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.

  2. Part 2: Evaluate the antitumor effect of Sym013 when administered at the RP2D and regimen to patients. [ Time Frame: 24 months ]
    Documented objective response (OR) (defined as partial response [PR] or complete response [CR]) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at any time during trial participation.


Secondary Outcome Measures :
  1. Part 1: Determine the RP2D and regimen of Sym013. [ Time Frame: 24 months ]
    Determination based on evaluation of the patient data for DLTs from Part 1.

  2. 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.

  3. Parts 1 and 2: Area under the concentration-time curve in a dosing interval (AUC). [ Time Frame: 42 Months ]
    Will be estimated using non-compartmental methods and actual time points.

  4. Parts 1 and 2: Maximum concentration (Cmax). [ Time Frame: 42 Months ]
    Will be derived from observed data.

  5. Parts 1 and 2: Time to reach maximum concentration (Tmax). [ Time Frame: 42 months ]
    Will be derived from observed data.

  6. Parts 1 and 2: Trough concentration (Ctrough). [ Time Frame: 42 Months ]
    Will be derived from observed data.

  7. Parts 1 and 2: Elimination half-life (T½). [ Time Frame: 42 Months ]
    Will be estimated using non-compartmental methods and actual time points.

  8. Parts 1 and 2: Clearance (CL). [ Time Frame: 42 Months ]
    Will be estimated using non-compartmental methods and actual time points.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

    1. Primary malignancies of the CNS
    2. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02906670


Contacts
Contact: Ulla Holm Hansen, RN +45 2487 0020 uhh@symphogen.com
Contact: Ivan Horak, MD +45 2055 2604 idh@symphogen.com

Locations
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Jordan Berlin, MD    800-811-8480    jordan.berlin@vanderbilt.edu   
Principal Investigator: Jordan Berlin, MD         
United States, Texas
South Texas Accelerated Research Therapeutics, LLC Recruiting
San Antonio, Texas, United States, 78229
Contact: Isabel Jimenez, RN, MSN    210-593-5252    isabel.jimenez@start.stoh.com   
Principal Investigator: Amita Patnaik, MD         
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78240
Contact: Sarah Gomez    210-595-5670      
Principal Investigator: Anthony W Tolcher, MD         
Sponsors and Collaborators
Symphogen A/S
Investigators
Principal Investigator: Jordan Berlin, MD Vanderbilt University Medical Center

Responsible Party: Symphogen A/S
ClinicalTrials.gov Identifier: NCT02906670     History of Changes
Other Study ID Numbers: Sym013-01
First Posted: September 20, 2016    Key Record Dates
Last Update Posted: July 19, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Keywords provided by Symphogen A/S:
Epithelial malignancies

Additional relevant MeSH terms:
Neoplasms