NCT03549338

Sym004 Versus Futuximab or Modotuximab in Patients With mCRC

A Ph2, Randomized, Open-Label, Multicenter, Three-Arm Trial of Sym004 Versus Each of Its Component Futuximab and Modotuximab, in Patients With Chemotherapy-Refractory Metastatic Colorectal Carcinoma and Acquired Resistance to Anti-EGFR mAb

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Symphogen A/S · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 2, randomized, open-label, 3-arm trial in the ratio of 1:1:1 to either Sym004 (Arm A) versus each of its component monoclonal antibodies (mAbs), futuximab (Arm B) or modotuximab (Arm C), in genomically-selected patients with chemotherapy-refractory metastatic colorectal carcinoma (mCRC) and acquired resistance to anti-epidermal growth factor receptor (anti-EGFR) mAb therapy. The study is designed to evaluate the relative antitumor activity of each agent as assessed by imaging studies performed after 8 weeks of treatment.

Detailed description

Following consent and prior to randomization, genomic analysis will be conducted on blood samples obtained from each potential patient. Triple-negative (TN) results as defined in trial eligibility criteria will be required for initial eligibility. Patients with TNmCRC will continue in the screening process. Once deemed fully eligible, patients will be randomized to Arm A, Arm B, or Arm C. Dosing cycles of 28 days will continue until documented disease progression (PD) or another criterion for discontinuation is met. Antitumor activity will be assessed at the end of every 2 cycles (every 8 weeks \[Q8W\]). At the End of Cycle 2 (EOC2) tumor assessment: * Patients assigned to Arm A (Sym004) with a documented objective response (OR) or stable disease (SD) will continue to receive Sym004; patients at the EOC2 with documented PD will be discontinued from study * Patients assigned to Arm B (futuximab) or Arm C (modotuximab) with a documented OR or SD will be crossed-over to receive Sym004; patients with documented PD at the EOC2 (or prior to the EOC2) will be offered the opportunity to crossover to receive Sym004 or will be discontinued from study To be considered evaluable for antitumor activity assessment, patients must have completed 2 cycles of dosing inclusive of EOC2 disease imaging studies and must have received any amount of their assigned investigational medicinal product (IMP) during that period, or have PD documented by imaging studies prior to the EOC2. Non-evaluable patients and patients discontinuing from study prior to the EOC2 for reasons other than documented PD will not be replaced. Note: In December 2018, the decision was made to terminate the trial and enrollment was prematurely discontinued. The primary, secondary, and exploratory objectives are no longer applicable. Only clinical safety-related evaluations will be conducted.

Conditions

• Metastatic Colorectal Cancer
• Colorectal Cancer Metastatic
• Carcinoma

Interventions

Type	Name	Description
DRUG	Sym004	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.
DRUG	Futuximab	Futuximab is one of two mAb components that constitute Sym004.
DRUG	Modotuximab	Modotuximab is one of two mAb components that constitute Sym004.

Timeline

• Start date: 2018-11-29
• Primary completion: 2019-03-01
• Completion: 2019-03-09
• First posted: 2018-06-08
• Last updated: 2020-09-28
• Results posted: 2020-01-14

Locations

18 sites across 4 countries: United States, Germany, Italy, Spain

Regulatory

• FDA-regulated drug study