Metastatic Colorectal CancerPhase 2NCT03549338
Sym004 Versus Futuximab or Modotuximab in Patients With mCRC
A Phase 2 study testing Sym004, Futuximab and Modotuximab in people with Metastatic Colorectal Cancer and Colorectal Cancer Metastatic, run by Symphogen A/S at 18 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer, Colorectal Cancer Metastatic, Carcinoma
- What is being tested?
- Sym004, Futuximab and Modotuximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 18 sitesin 4 countries
- Study dates
- 29 Nov 2018to 9 Mar 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
18 sites in 4 countries.
18 sites in 4 countries
United States5 sites
Emory University Hospital
Atlanta, Georgia, 30322
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of North Carolina - Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
City of Hope - Comprehensive Cancer Center
Duarte, California, 91010
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Germany5 sites
Uniklinik Dresden
Dresden, 01307
Universitaetsklinikum Essen
Essen, 45147
Asklepios Kliniken Altona
Hamburg, 22763
Universitätsmedizin Mannheim
Mannheim, 68167
Städtisches Klinikum München
München, 81737
Spain5 sites
Hospital del Mar
Barcelona, 08003
Vall d'Hebron Institut d'Oncologia (VHIO)
Barcelona, 08035
Institut Català d'Oncologia
Barcelona, 08908
Hospital Universitario HM Sanchinarro
Madrid, 28050
Hospital Clínico de Valencia
Valencia, 46010
Italy3 sites
ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale"
Naples, 80131
Università degli Studi della Campania "Luigi Vanvitelli"
Naples, 80131
About this study
Official title: 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
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.
Read the 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.
- Being tested
- Sym004, Futuximab, Modotuximab
- Keywords
- Metastatic Colorectal Cancer, Colorectal Cancer, Carcinoma, Sym004, futuximab, modotuximab
- Medical subject headings
- Colorectal Neoplasms, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sym004Drug
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.
FutuximabDrug
Futuximab is one of two mAb components that constitute Sym004.
ModotuximabDrug
Modotuximab is one of two mAb components that constitute Sym004.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: 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. Receives: Drug: Modotuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2018
- Study start29 Nov 2018
- Primary completion1 Mar 2019
- Study completion9 Mar 2019
Why it stopped: Study was terminated due to administrative reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Symphogen A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Scott Kopetz, MD,PhD,FACP, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03549338
- Sponsor's protocol ID
- Sym004-13
- Other IDs
- 2018-000618-39, 2018
- Status last verified
- Sep 2020
- First submitted
- 25 May 2018
- Last updated
- 28 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03549338
- Acronym / sponsor ID
- Sym004-13
- Keywords
- Metastatic Colorectal Cancer, Colorectal Cancer, Carcinoma, Sym004, futuximab, modotuximab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to administrative reasons
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Symphogen A/SIndustry (pharma, biotech, devices)
- Study start
- 29 Nov 2018 (actual)
- Primary completion
- 1 Mar 2019 (actual)
- Study completion
- 9 Mar 2019 (actual)
- First posted
- 8 Jun 2018 (actual)
- Results
- Posted 14 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A (Sym004) | Experimental | Drug: Sym004Sym004 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. |
| Arm B (Futuximab) | Experimental | Drug: FutuximabFutuximab 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). |
| Arm C (Modotuximab) | Experimental | Drug: ModotuximabModotuximab 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sym004Sym004 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 | Arm A (Sym004) |
| FutuximabFutuximab is one of two mAb components that constitute Sym004. | Drug | Arm B (Futuximab) |
| ModotuximabModotuximab is one of two mAb components that constitute Sym004. | Drug | Arm C (Modotuximab) |
Primary outcome
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence.
Time frame: 4 months
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Kopetz, MD,PhD,FACP principal investigator
M.D. Anderson Cancer Center
18 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sym004, Futuximab and Modotuximab in people with Metastatic Colorectal Cancer and Colorectal Cancer Metastatic, run by Symphogen A/S at 18 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Germany, Spain, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs) by Nature, Severity, and Occurrence. (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2020.