Sym004 Versus TAS-102 in Patients With mCRC

NCT03717038 | Withdrawn Phase 3 DMC FDA Drug

• 2 other identifiers: Sym004-122018-003187-31
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer; Colorectal Cancer Metastatic; Carcinoma

Keywords

Metastatic Colorectal Cancer; Colorectal Cancer Metastatic; Carcinoma; Sym004; futuximab; modotuximab; TAS-102; Trifluridine; Tipiracil; Lonsurf

Outcome Measures

Primary Outcomes (1)

• 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.

  Assessed up to 5 years.

Secondary Outcomes (8)

• Antineoplastic Efficacy: Progression Free Survival (PFS) as assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

  Assessed up to 5 years.

• Antineoplastic Efficacy: Objective Response Rate (ORR) as assessed by RECIST v1.1.

  Assessed up to 5 years.

• Antineoplastic Efficacy: Disease Control Rate (DCR) as assessed by RECIST v1.1.

  Assessed up to 5 years.

• Antineoplastic Efficacy: Duration of Response (DOR) as assessed by RECIST v1.1.

  Assessed up to 5 years.

• Sym004 Safety Evaluation: Occurrence and nature of adverse events (AEs) on a weekly dosing regimen.

  Assessed up to 5 years.

Study Arms (2)

Arm A (Sym004)

EXPERIMENTAL

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

Arm B (TAS-102)

ACTIVE COMPARATOR

TAS-102 is commercially available and will be administered as per local prescribing instructions.

Drug: TAS-102

Interventions

Sym004 DRUG

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.

Arm A (Sym004)

TAS-102 DRUG

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

Arm B (TAS-102)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, ≥ 18 years of age (≥ 20 years of age in Japan) at the time of obtaining informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (or equivalent Karnofsky PS of 70% to 100%).
• Histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is metastatic.
• Meeting the protocol definition of DNmCRC as assessed in the screening blood test.
• mCRC not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
• Measurable or non-measurable disease according to the Response Evaluation Criteria in Solid Tumors (Version 1.1) (RECIST v1.1).
• Persons of childbearing potential agreeing to use a highly effective method of contraception during the study, beginning within 2 weeks prior to the first dose of protocol therapy and continuing until 3 months after the last dose of Sym004 or 6 months after the last dose of TAS-102; male patients must also agree to refrain from sperm donation during these periods.

You may not qualify if:

• Women who are pregnant or intending to become pregnant before, during, or within 3 months after the last dose of Sym004 or 6 months after the last dose of TAS-102; women who are breastfeeding.
• Prior history of specific mutations (specified in the protocol) in the tumor tissue at the time of any previous assessment.
• Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
• An active second malignancy or history of another malignancy within 5 years prior to randomization, with exceptions.
• Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism, within 4 weeks prior to randomization, unless adequately treated and considered by the Investigator to be stable.
• Active uncontrolled bleeding or a known bleeding diathesis.
• Known clinically significant cardiovascular disease or condition.
• Non-healing wounds on any part of the body.
• Significant gastrointestinal abnormality.
• Skin rash of Grade \> 1 from prior anti-EGFR or other therapy at the time of randomization.
• Any other unresolved Grade \> 1 toxicity associated with prior antineoplastic therapy, with exceptions.
• Known or suspected hypersensitivity to any of the excipients of formulated Sym004 or TAS-102.
• Prior treatment with either TAS-102 or regorafenib.
• Antineoplastic agents for the primary malignancy (standard or investigational) within 3 weeks prior to randomization and during study; includes chemotherapy, immunotherapy, or other biological therapy.
• Other investigational treatments within 3 weeks prior to randomization and during study; includes participation in medical device or other therapeutic intervention clinical trial.

Sponsors & Collaborators

• Symphogen A/S: lead

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma

Interventions

futuximab; trifluridine tipiracil drug combination

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Josep Tabernero, MD, PhD

  Vall d'Hebron Institute of Oncology (VHIO)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: October 23, 2018
• Study Start: February 1, 2019
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2025
• Last Updated: February 4, 2019

Record last verified: 2019-01