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

This study is currently recruiting participants.
Verified November 2017 by Symphogen A/S
Sponsor:
ClinicalTrials.gov Identifier:
NCT02906670
First Posted: September 20, 2016
Last Update Posted: November 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Symphogen A/S
  Purpose
This is the first study to test Sym013 (Pan-HER) in humans. The primary purpose of this study is to see if Pan-HER is safe and effective for patients with advanced epithelial malignancies without available therapeutic options.

Condition Intervention Phase
Oncology Drug: Sym013 Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group 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

Further study details as provided by Symphogen A/S:

Primary Outcome Measures:
  • Part 1: Assess the safety and tolerability of Pan-HER [ Time Frame: 12 months ]
    Evaluate dose-limiting toxicities measured during Cycle 1 of Pan-HER administration

  • Part 2: Confirm objective antitumor response [ Time Frame: 24 months ]
    Evaluate objective antitumor response by RECIST v1.1


Secondary Outcome Measures:
  • Evaluate the anti-drug antibody samples of patients treated with Pan-HER to determine if there is immunogenicity [ Time Frame: 36 months ]
  • Area under the concentration-time curve in a dosing interval (i.e. from time zero (end of infusion) [ Time Frame: 36 Months ]
  • Maximum concentration (Cmax) [ Time Frame: 36 Months ]
  • Time to reach maximum concentration (Tmax) [ Time Frame: 36 months ]
  • Trough concentration (Ctrough) [ Time Frame: 36 Months ]
  • Elimination half-life (T½) [ Time Frame: 36 Months ]
  • Clearance (CL) [ Time Frame: 36 Months ]
  • Last quantifiable concentration (Cz) [ Time Frame: 36 Months ]
  • Terminal rate constant [ Time Frame: 36 Months ]

Estimated Enrollment: 131
Study Start Date: October 2016
Estimated Study Completion Date: May 2020
Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1a Dose Escalation
Part 1 is a Phase 1a dose-escalation with Sym013 designed to determine the RP2D.
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: PET Expansion Cohort
An expansion cohort of patients with FDG-avid tumors will undergo pre- and post-dosing 18F-FDG PET imaging to evaluate the effects on tumor metabolism of Sym013 at the RP2D. Imaging to be paired with CT/MRI conducted for Disease Status Evaluation. Accrual to this cohort may occur concurrent with accrual to Part 2 of the study.
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. 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. 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. 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. 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

Detailed Description:

This is an open-label, multicenter trial composed of 2 parts in which Pan-HER will be evaluated when administered by the intravenous (IV) route on a weekly schedule in patients with advanced epithelial malignancies without available therapeutic options. Two (2) doses of Pan-HER administered every second week (Q2W) constitute 1 cycle.

Part 1 is a Phase 1a dose-escalation designed to determine the recommended phase 2 dose (RP2D).

Once the RP2D is selected, an expansion cohort of patients with fluorodeoxyglucose (FDG)-avid tumors will undergo pre- and post-dosing fluorine-18 radiolabeled FDG (18F-FDG) positron emission tomography (PET) imaging to evaluate the effects on tumor metabolism of Pan-HER when administered at this dose. Imaging to be paired with computed tomography (CT)/ magnetic resonance imaging (MRI) conducted for Disease Status Evaluation. Accrual to this cohort may occur concurrent with accrual to Part 2 of the study.

Part 2 is a Phase 2a dose-expansion at the RP2D. Four tumor types to be evaluated in this part 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. Patients will be entered, depending upon their underlying malignancy, to 1 of 4 corresponding expansion cohorts: Cohort A, Cohort B, Cohort C, or Cohort D.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
  • PET Expansion Cohort: Epithelial malignancy, measurable according to RECIST v1.1 that has been confirmed by 18F-FDG-PET imaging to be FDG-avid within 28 days prior to C1/D1

Additional inclusion criteria applicable to Part 2 ONLY:

  • Epithelial malignancy (types to be specified in a protocol amendment), 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:

Main exclusion criteria:

  • Any antineoplastic agent (standard or investigational) within 4 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 within 2 weeks prior to C1/D1 with allowed 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
  • Known central nervous system (CNS) or leptomeningeal metastases not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS 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
  • Any of the following within 2 weeks prior to C1/D1:

    • Any serious or uncontrolled infection
    • Any infection requiring parenteral antibiotics
    • Unexplained fever >38.0 °C
  Contacts and Locations
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         
Sponsors and Collaborators
Symphogen A/S
Investigators
Principal Investigator: Jordan Berlin, MD Vanderbilt University Medical Center
  More Information

Responsible Party: Symphogen A/S
ClinicalTrials.gov Identifier: NCT02906670     History of Changes
Other Study ID Numbers: Sym013-01
First Submitted: September 8, 2016
First Posted: September 20, 2016
Last Update Posted: November 24, 2017
Last Verified: November 2017
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