Sym013 (Pan-HER) in Patients With Advanced Epithelial Malignancies
- Conditions
- Oncology
- Interventions
- Drug: Sym013
- Registration Number
- NCT02906670
- Lead Sponsor
- Symphogen A/S
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 32
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
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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.
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Part 2 ONLY: Radiotherapy against target lesions within 4 weeks prior to C1/D1, unless there is documented progression of the lesion following radiotherapy
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Immunosuppressive or systemic hormonal therapy (>10 mg daily prednisone equivalent) within 2 weeks prior to C1/D1 with exceptions
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Use of hematopoietic growth factors within 2 weeks prior to C1/D1
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Active second malignancy or history of another malignancy within the last 3 years, with allowed exceptions
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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
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Inadequate recovery from an acute toxicity associated with any prior antineoplastic therapy
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Major surgical procedure within 4 weeks prior to C1/D1 or inadequate recovery from any prior surgical procedure
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Non-healing wounds on any part of the body
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Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks prior to C1/D1, unless adequately treated and stable
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Active uncontrolled bleeding or a known bleeding diathesis
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Significant gastrointestinal abnormalities
-
Significant cardiovascular disease or condition
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Abnormal hematologic, renal or hepatic function
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 mg/kg Q1W Sym013 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. 12 mg/kg Q2W + Prophylaxis Sym013 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. 6 mg/kg Q1W + Prophylaxis Sym013 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. 9 mg/kg Q1W + Prophylaxis Sym013 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. 2 mg/kg Q1W Sym013 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. 6 mg/kg Q2W Sym013 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. 9 mg/kg Q2W Sym013 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. Phase 2a Dose-Expansion Cohort A Sym013 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. Phase 2a Dose-Expansion Cohort C Sym013 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. Phase 2a Dose-Expansion Cohort D Sym013 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. 4 mg/kg Q1W Sym013 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. 9 mg/kg Q2W + Prophylaxis Sym013 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. 15 mg/kg Q2W + Prophylaxis Sym013 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. Phase 2a Dose-Expansion Cohort B Sym013 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.
- Primary Outcome Measures
Name Time Method Part 2: Evaluate the Antitumor Effect of Sym013 When Administered at the RP2D and Regimen to Patients. 24 months No data were collected for this Outcome Measures as Part 2 of the trial was never initiated.
Part 1: Assess the Safety and Tolerability of Sym013 When Administered Either Q1W or Q2W to Separate Dose-escalation Cohorts of Patients. 24 months Assess the occurrence of dose-limiting toxicities (DLTs) during Cycle 1 of Sym013 administration.
- Secondary Outcome Measures
Name Time Method Part 1: Determine the RP2D and Regimen of Sym013. 24 months No RP2D or regimen of Sym013 was determined as the trial was prematurely terminated
Parts 1 and 2: Evaluate the Immunogenicity of Sym013. 42 months Serum sampling to assess the potential for anti-drug antibody (ADA) formation was not analyzed as the trial was prematurely terminated
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 Will be derived from observed data.
Parts 1 and 2: Elimination Half-life (T½). 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W Will be estimated using non-compartmental methods and actual time points
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 Will be estimated using non-compartmental methods and actual time points.
Parts 1 and 2: Time to Reach Maximum Concentration (Tmax). 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W Will be derived from observed data. End of infusion was defined as time zero (0)
Parts 1 and 2: Clearance (CL). 0, 2, 4, 8, 24, 48, 168 hours and 336 hours if Q2W Will be estimated using non-compartmental methods and actual time points.
Trial Locations
- Locations (3)
NEXT Oncology
🇺🇸San Antonio, Texas, United States
South Texas Accelerated Research Therapeutics, LLC
🇺🇸San Antonio, Texas, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States