A Phase 3 interventional study of Sym004 and TAS-102 in Metastatic Colorectal Cancer, Colorectal Cancer Metastatic and Carcinoma, sponsored by Symphogen A/S. Withdrawn. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-02-04.
Sponsored by Symphogen A/S · Phase 3, Interventional, and Treatment
This is a Phase 3, randomized, open-label, 2-arm trial designed to evaluate overall survival (OS) following treatment with Sym004, an investigational medicinal product (IMP), versus TAS-102 (trifluridine/tipiracil), a comparator (control) agent.
Randomization is in the ratio of 1:1 to either Sym004 (Arm A) or TAS-102 (Arm B) in genomically-selected patients with chemotherapy-refractory or relapsed metastatic colorectal carcinoma (mCRC) and acquired resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) therapy.
Following consent, centralized genomic analysis will be conducted on blood samples obtained from each potential patient. Double-negative (DN) results as defined in trial inclusion criteria will be required for initial eligibility prior to randomization. Patients with DNmCRC will continue in the screening process. Once deemed fully eligible, patients will be randomized to either Arm A or Arm B (collectively referred to as protocol therapy).
Dosing cycles of 28 days with the assigned protocol therapy will continue until a protocol-specified discontinuation criterion is met. Following treatment discontinuation, patients will continue to be followed for OS.
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Exclusion Criteria:
Drugs and Other Treatments Exclusion Criteria:
Sym004 will be administered as a loading dose of 9 mg/kg on Cycle 1 Day 1, followed by weekly doses of 6 mg/kg beginning Cycle 1 Day 8.
Drug: Sym004
TAS-102 is commercially available and will be administered as per local prescribing instructions.
Drug: TAS-102
Sym004 is a 1:1 mixture of two recombinant mAbs (futuximab and modotuximab) which bind specifically to non-overlapping epitopes located in the extracellular domain (ECD) of the EGFR.
TAS-102 is a combination of trifluridine, a thymidine-based nucleic acid analogue, and tipiracil, a thymidine phosphorylase inhibitor.
Also known as: Trifluridine/Tipiracil, Lonsurf
Overall survival (OS) time following treatment with Sym004 versus TAS-102.
Time (in months) from the date of randomization to the date of death. In the absence of death confirmation or for patients alive as of the OS data cut-off date (i.e., date upon reaching 445 deaths), OS will be censored at the date of last study follow-up, or the cut-off date, whichever is earlier.
Time frame: Assessed up to 5 years.
Antineoplastic Efficacy: Progression Free Survival (PFS) as assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Time (in months) from the date of randomization until the date of the investigator-assessed radiological disease progression or death due to any cause. Investigator-assessed radiological disease progression (per RECIST v1.1) with the following key censoring rules: * Patients who are alive with no disease progression as of the analysis cut-off date will be censored at the date of the last tumor assessment. * Patients who receive non-study cancer treatment before disease progression will be censored at the date of the last evaluable tumor assessment before the initiation of non-study cancer treatment. * Patients with clinical, but not radiologic, evidence of progression will be censored at the date of the last evaluable tumor assessment before the clinical progression assessment.
Time frame: Assessed up to 5 years.
Antineoplastic Efficacy: Objective Response Rate (ORR) as assessed by RECIST v1.1.
Defined as the proportion of patients with objective evidence of complete response (CR) or partial response (PR). Assessed approximately every 8 weeks (at the end of even-numbered cycles).
Time frame: Assessed up to 5 years.
Antineoplastic Efficacy: Disease Control Rate (DCR) as assessed by RECIST v1.1.
Defined as the proportion of patients with objective evidence of CR, PR, or stable disease (SD). Assessed approximately every 8 weeks (at the end of even-numbered cycles).
Time frame: Assessed up to 5 years.
Antineoplastic Efficacy: Duration of Response (DOR) as assessed by RECIST v1.1.
Time (in months) from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause, with the same censoring rules as for PFS.
Time frame: Assessed up to 5 years.
Sym004 Safety Evaluation: Occurrence and nature of adverse events (AEs) on a weekly dosing regimen.
AEs will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology and the severity of the toxicities will be graded according to the Common Terminology Criteria for Adverse Events (Version 5) (CTCAE v5), where applicable, from signing of informed consent up to 30 days after the final dose of Sym004.
Time frame: Assessed up to 5 years.
Immunogenicity Assessment: Number of subjects with anti-drug antibodies (ADAs) to Sym004 over time.
Serum sampling to assess the potential for ADA formation are planned on the following visits: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Day 1 of odd numbered cycles thereafter, the End of Treatment Visit, and the 1-Month Follow-up Visit.
Time frame: Assessed up to 5 years.
Pharmacokinetic (PK) Parameters of Sym004: Trough Concentration (Cmin)
Cmin is defined as the serum concentration at the start of infusion. The serum concentration of Sym004 is the sum of the two constituting mAbs, futuximab and modotuximab. Sparse sampling at 7 timepoints are planned on the following visits: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 3 Day 1, End of Treatment Visit.
Time frame: Assessed up to 5 years.
Pharmacokinetic (PK) Parameters of Sym004: Maximum Concentration (Cmax)
Cmax is defined as the serum concentration at the end of infusion. The serum concentration of Sym004 is the sum of the two constituting mAbs, futuximab and modotuximab. Sparse sampling at 7 timepoints are planned on the following visits: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1, Cycle 3 Day 1, End of Treatment Visit.
Time frame: Assessed up to 5 years.
No study locations are listed for this record.
Plan to share: Undecided
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This study is withdrawn, as verified in Jan 2019. You cannot join it, but the record below documents what was studied.
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Symphogen A/S