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

NCT02906670 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: Sym013-01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

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.

Conditions

Oncology

Keywords

Epithelial malignancies

Outcome Measures

Primary Outcomes (2)

• 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.

  24 months

• 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.

  24 months

Secondary Outcomes (7)

• Part 1: Determine the RP2D and Regimen of Sym013.

  24 months

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

  42 months

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

  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.

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

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

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

Study Arms (14)

1 mg/kg Q1W

EXPERIMENTAL

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.

Drug: Sym013

2 mg/kg Q1W

EXPERIMENTAL

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.

Drug: Sym013

4 mg/kg Q1W

EXPERIMENTAL

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.

Drug: Sym013

6 mg/kg Q1W + Prophylaxis

EXPERIMENTAL

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.

Drug: Sym013

9 mg/kg Q1W + Prophylaxis

EXPERIMENTAL

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.

Drug: Sym013

6 mg/kg Q2W

EXPERIMENTAL

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.

Drug: Sym013

9 mg/kg Q2W

EXPERIMENTAL

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.

Drug: Sym013

9 mg/kg Q2W + Prophylaxis

EXPERIMENTAL

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.

Drug: Sym013

12 mg/kg Q2W + Prophylaxis

EXPERIMENTAL

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.

Drug: Sym013

15 mg/kg Q2W + Prophylaxis

EXPERIMENTAL

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.

Drug: Sym013

Phase 2a Dose-Expansion Cohort A

EXPERIMENTAL

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

Phase 2a Dose-Expansion Cohort B

EXPERIMENTAL

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

Phase 2a Dose-Expansion Cohort C

EXPERIMENTAL

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

Phase 2a Dose-Expansion Cohort D

EXPERIMENTAL

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

Interventions

Sym013 DRUG

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.

Also known as: Pan-HER

1 mg/kg Q1W; 12 mg/kg Q2W + Prophylaxis; 15 mg/kg Q2W + Prophylaxis; 2 mg/kg Q1W; 4 mg/kg Q1W; 6 mg/kg Q1W + Prophylaxis; 6 mg/kg Q2W; 9 mg/kg Q1W + Prophylaxis; 9 mg/kg Q2W; 9 mg/kg Q2W + Prophylaxis; Phase 2a Dose-Expansion Cohort A; Phase 2a Dose-Expansion Cohort B; Phase 2a Dose-Expansion Cohort C; Phase 2a Dose-Expansion Cohort D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Symphogen A/S: lead

Study Sites (3)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

NEXT Oncology

San Antonio, Texas, 78240, United States

Location

Related Publications (1)

• 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.

  PMID: 35113285 DERIVED

MeSH Terms

Conditions

Neoplasms

Results Point of Contact

• Title: Medical Director
• Organization: Symphogen AS

info@symphogen.com

004545265050

Study Officials

• Jordan Berlin, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2016
• First Posted: September 20, 2016
• Study Start: November 1, 2016
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: August 28, 2020
• Results First Posted: August 28, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)