Clinical Trial: NCT02906670 - My Cancer Genome

NCT02906670

Description:

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.

Related Conditions:

Malignant Solid Tumor

Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT02906670

Trial Eligibility

Document

Title

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

Clinical Trial IDs

ORG STUDY ID: Sym013-01
NCT ID: NCT02906670

Conditions

Oncology

Interventions

Drug	Synonyms	Arms
Sym013	Pan-HER	1 mg/kg Q1W

Purpose

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.

Trial Arms

Name	Type	Description	Interventions
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Sym013

Eligibility 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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:	Part 1: Determine the RP2D and Regimen of Sym013.
Time Frame:	24 months
Safety Issue:
Description:	No RP2D or regimen of Sym013 was determined as the trial was prematurely terminated

Measure:	Parts 1 and 2: Evaluate the Immunogenicity of Sym013.
Time Frame:	42 months
Safety Issue:
Description:	Serum sampling to assess the potential for anti-drug antibody (ADA) formation was not analyzed as the trial was prematurely terminated

Measure:	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
Safety Issue:
Description:	Will be estimated using non-compartmental methods and actual time points.

Measure:	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
Safety Issue:
Description:	Will be derived from observed data.

Measure:	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
Safety Issue:
Description:	Will be derived from observed data. End of infusion was defined as time zero (0)

Measure:	Parts 1 and 2: Elimination Half-life (T½).
Time Frame:	0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
Safety Issue:
Description:	Will be estimated using non-compartmental methods and actual time points

Measure:	Parts 1 and 2: Clearance (CL).
Time Frame:	0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W
Safety Issue:
Description:	Will be estimated using non-compartmental methods and actual time points.

Details

Phase:	Phase 1/Phase 2
Primary Purpose:	Interventional
Overall Status:	Terminated
Lead Sponsor:	Symphogen A/S

Trial Keywords

Epithelial malignancies

Last Updated

August 28, 2020

Clinical Trials /

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