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OncologyPhase 1/2NCT02906670

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

A Phase 1/2 study testing Sym013 in people with Oncology, run by Symphogen A/S at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Oncology
What is being tested?
Sym013
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
3 sitesUnited States
Study dates
1 Nov 2016to Jun 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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:
Show all 16Show fewer
  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • South Texas Accelerated Research Therapeutics, LLC

    San Antonio, Texas, 78229

  • NEXT Oncology

    San Antonio, Texas, 78240

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
Oncology
Being tested
Sym013
Keywords
Epithelial malignancies
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sym013Drug

    Also called Pan-HER

    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.

Study groups in NCT02906670
Study groupRoleWhat they receive
1 mg/kg Q1WExperimentalPhase 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.
Receives: Drug: Sym013
2 mg/kg Q1WExperimentalPhase 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.
Receives: Drug: Sym013
4 mg/kg Q1WExperimentalPhase 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.
Receives: Drug: Sym013
6 mg/kg Q1W + ProphylaxisExperimentalPhase 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.
Receives: Drug: Sym013
9 mg/kg Q1W + ProphylaxisExperimentalPhase 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.
Receives: Drug: Sym013
6 mg/kg Q2WExperimentalPhase 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.
Receives: Drug: Sym013
9 mg/kg Q2WExperimentalPhase 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.
Receives: Drug: Sym013
9 mg/kg Q2W + ProphylaxisExperimentalPhase 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.
Receives: Drug: Sym013
12 mg/kg Q2W + ProphylaxisExperimentalPhase 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.
Receives: Drug: Sym013
15 mg/kg Q2W + ProphylaxisExperimentalPhase 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.
Receives: Drug: Sym013
Phase 2a Dose-Expansion Cohort AExperimentalPart 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.
Receives: Drug: Sym013
Phase 2a Dose-Expansion Cohort BExperimentalPart 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.
Receives: Drug: Sym013
Phase 2a Dose-Expansion Cohort CExperimentalPart 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.
Receives: Drug: Sym013
Phase 2a Dose-Expansion Cohort DExperimentalPart 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.
Receives: Drug: Sym013

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1: Assess the Safety and Tolerability of Sym013 When Administered Either Q1W or Q2W to Separate Dose-escalation Cohorts of Patients.

    Assess the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym013 administration.

    Measured: 24 months

  2. Part 2: Evaluate the Antitumor Effect of Sym013 When Administered at the RP2D and Regimen to Patients.

    No data were collected for this Outcome Measures as Part 2 of the trial was never initiated.

    Measured: 24 months

Secondary outcomes (7)
  1. Part 1: Determine the RP2D and Regimen of Sym013.

    No RP2D or regimen of Sym013 was determined as the trial was prematurely terminated

    Measured: 24 months

  2. Parts 1 and 2: Evaluate the Immunogenicity of Sym013.

    Serum sampling to assess the potential for anti-drug antibody (ADA) formation was not analyzed as the trial was prematurely terminated

    Measured: 42 months

  3. Parts 1 and 2: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC).

    Will be estimated using non-compartmental methods and actual time points.

    Measured: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W

  4. Parts 1 and 2: Maximum Concentration (Cmax) and Trough Concentration (Ctrough) - Mean Values.

    Will be derived from observed data.

    Measured: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W

  5. Parts 1 and 2: Time to Reach Maximum Concentration (Tmax).

    Will be derived from observed data. End of infusion was defined as time zero (0)

    Measured: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W

  6. Parts 1 and 2: Elimination Half-life (T½).

    Will be estimated using non-compartmental methods and actual time points

    Measured: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W

  7. Parts 1 and 2: Clearance (CL).

    Will be estimated using non-compartmental methods and actual time points.

    Measured: 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2016 (estimated)
  2. Study start1 Nov 2016
  3. Primary completionJun 2019
  4. Study completionJun 2019

Why it stopped: Business reasons

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02906670
Sponsor's protocol ID
Sym013-01
Status last verified
Aug 2020
First submitted
8 Sep 2016
Last updated
28 Aug 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Berlin J, Tolcher AW, Ding C, Whisenant JG, Horak ID, Wood DL, Nadler PI, Hansen UH, Lantto J, Skartved NJO, Pedersen MW, Patnaik A. First-in-human trial exploring safety, antitumor activity, and pharmacokinetics of Sym013, a recombinant pan-HER antibody mixture, in advanced epithelial malignancies. Invest New Drugs. 2022 Jun;40(3):586-595. doi: 10.1007/s10637-022-01217-7. Epub 2022 Feb 3.

    PubMed 35113285

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Sym013 in people with Oncology, run by Symphogen A/S at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02906670, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2020.

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