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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| Sym013 | Pan-HER | Phase 1a Dose Escalation |
Purpose
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.
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 designed to determine the recommended phase 2 dose
(RP2D). Patients entered to Dose Level 1, 2, and 3 were treated every week (Q1W). As of April
2017, the dosing schedule in this trial has been changed to every second week (Q2W). Patients
entered to the trial prior to implementation of this amendment will continue to be treated
Q1W.
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 Sym013 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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Phase 1a Dose Escalation | Experimental | Part 1 is a Phase 1a dose-escalation with Sym013 designed to determine the RP2D. Sym013 will be tested potentially in eight dose titration cohorts. | |
| PET Expansion Cohort | Experimental | 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. | |
| Phase 2a Dose Expansion Cohort A | Experimental | 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. | |
| Phase 2a Dose Expansion Cohort B | Experimental | 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. | |
| Phase 2a Dose Expansion Cohort C | Experimental | 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. | |
| Phase 2a Dose Expansion Cohort D | Experimental | 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. | |
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
- 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:
- 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 (>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; known, untreated CNS or leptomeningeal
metastases, or spinal cord compression, any of the above 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
| 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 Q1W and Q2W to patients with advanced epithelial malignancies without available therapeutic options |
| Time Frame: | 18 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 of Sym013 |
| Time Frame: | 18 months |
| Safety Issue: | |
| Description: | Determination based on evaluation of the patient data for DLTs from Part 1. |
| 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. |
| Measure: | Parts 1 and 2: Area under the concentration-time curve in a dosing interval (AUC) |
| Time Frame: | 42 Months |
| Safety Issue: | |
| Description: | Will be estimated using non-compartmental methods and actual time points. |
| Measure: | Parts 1 and 2: Maximum concentration (Cmax) |
| Time Frame: | 42 Months |
| Safety Issue: | |
| Description: | Will be derived from observed data. |
| Measure: | Parts 1 and 2: Time to reach maximum concentration (Tmax) |
| Time Frame: | 42 months |
| Safety Issue: | |
| Description: | Will be derived from observed data. |
| Measure: | Parts 1 and 2: Trough concentration (Ctrough) |
| Time Frame: | 42 Months |
| Safety Issue: | |
| Description: | Will be derived from observed data. |
| Measure: | Parts 1 and 2: Elimination half-life (T½) |
| Time Frame: | 42 Months |
| Safety Issue: | |
| Description: | Will be estimated using non-compartmental methods and actual time points. |
| Measure: | Parts 1 and 2: Clearance (CL) |
| Time Frame: | 42 Months |
| 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: | Recruiting |
| Lead Sponsor: | Symphogen A/S |
Trial Keywords
Last Updated
February 21, 2018
