Sym004 Versus Futuximab or Modotuximab in Patients With mCRC

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Metastatic Colorectal Cancer, Colorectal Cancer, Carcinoma, Sym004, futuximab, modotuximab Read More

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.