Sym004 Versus Futuximab or Modotuximab in Patients With mCRC

• Status: Terminated
• Trial end date: 2019-03-09
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Symphogen A/S
• Treatments: Antibodies

Criteria

Inclusion Criteria:

• Male or female patients, ≥ 18 years of age at the time of obtaining informed consent.

• Histologically- or cytologically-confirmed mCRC.

• Microsatellite instability-high (MSI-H) / mismatch repair-deficient (dMMR) tumors must have received prior therapy with pembrolizumab, nivolumab, or other programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway blocker, and must have progressed on that therapy.

• Meeting the protocol definition of TNmCRC assessed in the screening blood test.

• mCRC currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.

• Measurable disease according to RECIST v1.1, and willingness to undergo a total of 2 biopsies of a primary or metastatic tumor site(s) considered safely accessible for biopsy.

• Must have received at least 2 prior regimens of standard chemotherapy for mCRC and must have been refractory to or failed (includes intolerance to) those regimens. Prior standard chemotherapy may not have included TAS-102 or regorafenib, but must have included agents as specified in the protocol.

• "Acquired" resistance to commercially available anti-EGFR mAbs approved for the treatment of mCRC must have:

1. Received treatment with an anti-EGFR for ≥16 weeks

2. Progressive disease (PD) documented by imaging or clinical findings less than or equal to 6 calendar months after cessation of previous anti-EGFR mAb treatment

3. No more than 6 calendar months from last dose of previous anti-EGFR mAb treatment to date of consent for this trial (regardless of the line of therapy in which it was used)

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

• Not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 3 months after the last dose of study drug.

Exclusion Criteria:

• Women who are pregnant or lactating or intending to become pregnant before, during, or within 3 months after the last dose of study drug.

• Prior history of specific mutations (specified in the protocol) in the tumor 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 the last 5 years, with exceptions.

• Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to first administration of study drug 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 > Grade 1 from prior anti-EGFR therapy at the time of randomization.

• Unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy

Drugs and Other Treatments Exclusion Criteria:

• Prior treatment with TAS-102 or regorafenib

• Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks prior to first administration of IMP and during study with exceptions

• Any other investigational treatments within 4 weeks prior to and during study; includes participation in any medical device or other therapeutic intervention clinical trials

• Radiotherapy as specified in the protocol

• Immunosuppressive or systemic hormonal therapy (> 10 mg daily prednisone equivalent) within 2 weeks prior to first administration of IMP and during study; allowed therapies are specified in the protocol.