Sym004 Versus Futuximab or Modotuximab in Patients With mCRC

NCT03549338 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: Sym004-132018-000618-39
• Study Type: interventional
• Target: 2
• Locations: 4 countries
• Sites: 18

Brief 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.

Conditions

Metastatic Colorectal Cancer; Colorectal Cancer Metastatic; Carcinoma

Keywords

Metastatic Colorectal Cancer; Colorectal Cancer; Carcinoma; Sym004; futuximab; modotuximab

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence.

  Measured From Baseline to End of Trial Participation, as Assessed by the Common Terminology Criteria for AEs (Version 5) (CTCAE v5). 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 CTCAE v5, where applicable.

  4 months

Study Arms (3)

Arm A (Sym004)

EXPERIMENTAL

Sym004 will be given as a loading dose of 9 mg/kg on Cycle 1 Day 1 (C1D1), followed by weekly doses of 6 mg/kg beginning C1D8. For patients that crossover from Arm B and Arm C, Sym004 will be given at the dose level that contains the corresponding dose level of the respective individual antibody (futuximab or modotuximab) prior to crossover.

Drug: Sym004

Arm B (Futuximab)

EXPERIMENTAL

Futuximab will be given as a loading dose of 4.5 mg/kg on C1D1, followed by weekly doses of 3 mg/kg beginning C1D8. At the End of Cycle 2 (EOC2), ongoing patients will crossover to Sym004; crossover may occur prior to the EOC2 in the event of early radiographic documentation of progressive disease (PD).

Drug: Futuximab

Arm C (Modotuximab)

EXPERIMENTAL

Modotuximab will be given as a loading dose of 4.5 mg/kg on C1D1, followed by weekly doses of 3 mg/kg beginning C1D8. At the EOC2, ongoing patients will crossover to Sym004; crossover may occur prior to the EOC2 in the event of early radiographic documentation of PD.

Drug: Modotuximab

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)

Futuximab DRUG

Futuximab is one of two mAb components that constitute Sym004.

Arm B (Futuximab)

Modotuximab DRUG

Modotuximab is one of two mAb components that constitute Sym004.

Arm C (Modotuximab)

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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Symphogen A/S: lead

Study Sites (18)

City of Hope - Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of North Carolina - Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Uniklinik Dresden

Dresden, 01307, Germany

Location

Universitaetsklinikum Essen

Essen, 45147, Germany

Location

Asklepios Kliniken Altona

Hamburg, 22763, Germany

Location

Universitätsmedizin Mannheim

Mannheim, 68167, Germany

Location

Städtisches Klinikum München

München, 81737, Germany

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

Napoli, 80131, Italy

Location

Università degli Studi della Campania "Luigi Vanvitelli"

Napoli, 80131, Italy

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Vall d'Hebron Institut d'Oncologia (VHIO)

Barcelona, 08035, Spain

Location

Institut Català d'Oncologia

Barcelona, 08908, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma

Interventions

futuximab

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

Limitations and Caveats

Early termination changed the primary objective to assess the safety of the allocated treatment. Collection of data for secondary and exploratory objectives was omitted. The crossover dose plan as detailed was no longer in effect.

Results Point of Contact

• Title: Vice President, Global Oncology
• Organization: Symphogen A/S

info@symphogen.com

+45 8838 2600

Study Officials

• Scott Kopetz, MD,PhD,FACP

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2018
• First Posted: June 8, 2018
• Study Start: November 29, 2018
• Primary Completion: March 1, 2019
• Study Completion: March 9, 2019
• Last Updated: September 28, 2020
• Results First Posted: January 14, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3); ES (5); DE (5); US (5)