Metastatic Colorectal CancerPhase 2EGIA-003NCT06225843
Sotevtamab (AB-16B5) Combined With FOLFOX as Neoadjuvant Treatment Prior to Resection of Colorectal Cancer Liver Metastasis
A Phase 2 study testing Sotevtamab and FOLFOX in people with Metastatic Colorectal Cancer, run by Alethia Biotherapeutics at 1 site in Canada.
Trial summary
This Phase II study will recruit 17 colorectal cancer patients with liver-dominant metastases. All recruited patients will receive Sotevtamab at a dose of 800 mg once weekly for 6 cycles combined with FOLFOX once every 2 weeks for the first 4 cycles followed by liver metastases resection surgery with or without… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Sotevtamab and FOLFOX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteCanada
- Study dates
- 15 Feb 2024to Jun 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Participants (male or non-pregnant female) must be ≥ 18 years of age on the day of signing the informed consent.
- Participants with stage IV colon or rectal adenocarcinoma with resectable liver-dominant metastases and candidate to neoadjuvant FOLFOX followed by partial hepatectomy.
- Participants may have had resection of their primary colon or rectal adenocarcinoma in the past or will have their primary cancer resected at the same time as the liver metastases resection or after liver metastases resection.
- Participants must not have received prior chemotherapy for metastatic disease. Prior adjuvant chemotherapy and radiotherapy following resection of primary tumor is acceptable if completed at least 12 months prior to trial enrolment.
- For multiple liver metastases, participants may undergo liver metastases needle-ablation of some metastases combined with surgical resection of others, as long as at least one metastasis is surgically resected.
- Participants with at least one measurable lesion according to RECIST 1.1.
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- Participants must have a liver metastasis amenable for biopsy with no contraindication for biopsy.
- Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
- Participants must have recovered from the toxic effects resulting from the most recent cancer treatment to Grade 1 or less. If the participants underwent major surgery, they must have recovered from the complications and/or toxicity.
- Participants must have a life expectancy of at least 3 months.
- Participants must have adequate organ and immune function
- Female participants of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of trial treatment.
- Participants (both male and female) of reproductive potential must be willing to practice highly effective methods of contraception throughout the trial and for up to 90 days after the last dose of trial medication. Abstinence is acceptable if this is the participant's usual lifestyle.
- Female participants are not considered of childbearing potential if they have a history of surgical sterility or evidence of post-menopausal status defined as any of the following:
- ≥ 45 years of age and has not had menses for more than 2 years
- Amenorrheic for less than 2 years without hysterectomy and oophorectomy and a follicle stimulating hormone (FSH) value in the postmenopausal range at screening
- Post hysterectomy, oophorectomy, or tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or by ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.
- Participants must understand and be able and willing and likely to fully comply with the trial procedures, including scheduled follow-up, and restrictions.
- Participants must have given written personally signed and dated informed consent to participate in the trial in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines, before completing any trial related procedures.
Who cannot join
- Participants who have received prior therapy with sotevtamab
- Concurrent administration of anti-VGFR, anti-EGFR, anti-VEGF or other biological or targeted therapy with neoadjuvant FOLFOX
- Participants with MMR-deficient primary colorectal tumor
- Hereditary colorectal cancer (e.g., familial colonic polyposis or Lynch syndrome)
- Participants who have another malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer.
- Participants who are expected to require any other form of systemic or localized antineoplastic therapy while on the trial. This includes maintenance therapy with another agent or radiation therapy.
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- Participants who are receiving a dose > 10 mg/day of prednisone (or equivalent) within 7 days prior to the first dose of study treatment or any other form of immunosuppressive medication.
- Participants who are currently participating or have participated in a trial of an investigational agent or using an investigational device within 21 days of the first dose of trial treatment. The 21-day window should be calculated using the last dose of an investigational agent or last use of an investigational device.
- Participants who have a pre-existing peripheral sensitive neuropathy with functional impairment.
- Participants with clinically significant electrocardiogram (ECG) abnormalities.
- Participants who have received or will receive a live vaccine with 30 days prior to the first dose of trial treatment.
- Participants with a known history of human immunodeficiency (HIV).
- Participants with an active Hepatitis B or C infection.
- Participants with an active infection requiring antibiotic therapy.
- Participants with a known history of alcohol or other substance abuse within the last year.
- Participants with known hypersensitivity to FOLFOX.
- Participants who have a history or current evidence of any condition, therapy or laboratory abnormalities that may confound the results of the trial, interfere with the participant's participation for the full duration of the trial or if it is not in the best interest of the participant to participate in the trial.
- Participants with medical, social or psychosocial factors that, in the opinion of the treating Investigator, could impact the safety or compliance with trial procedures.
- Participants who are pregnant or lactating or who are expecting to conceive or father children within the projected duration of the trial through 90 days after the last dose of sotevtamab or 180 days after the last dose of FOLFOX.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Centre Hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, H2X 3E4
Mustapha Tehfé, MD
About this study
Official title: A Proof-of-Concept Phase II Trial to Evaluate the EMT Inhibitor Sotevtamab Combined With FOLFOX Administered as Neoadjuvant Treatment Prior to Resection of Colorectal Cancer Liver Metastasis
This Phase II study will recruit 17 colorectal cancer patients with liver-dominant metastases. All recruited patients will receive Sotevtamab at a dose of 800 mg once weekly for 6 cycles combined with FOLFOX once every 2 weeks for the first 4 cycles followed by liver metastases resection surgery with or without primary cancer resection. One cycle of treatment will consist of 14 days (2 weeks).
Read the detailed description
This is an open-label, single-arm, single-center proof-of-concept Phase II trial of sotevtamab in combination with FOLFOX-based preoperative neoadjuvant systemic chemotherapy in participants with resectable liver-dominant metastases and candidate to neoadjuvant FOLFOX followed by partial hepatectomy. Approximately 17 participants will be enrolled in this trial and will receive 4 cycles of FOLFOX (Cycle 1 to Cycle 4) as preoperative systemic chemotherapy and 6 cycles of sotevtamab (Cycle 1 to Cycle 6). One cycle of treatment will consist of 14 days (2 weeks). Sotevtamab will be administered by intravenous (IV) infusion at 800 mg on Day 1 and Day 8 of each cycle. FOLFOX will be administered on Day 1 of Cycle 1 to Cycle 4 as follows: oxaliplatin 85 mg/m² IV infusion + leucovorin 400 mg/m² IV infusion + 5-Fluorouracil (5-FU) 400 mg/m² IV bolus + 5-FU 2400 mg/m² continuous IV infusion over 46 hours. Participants will undergo liver metastasis resection with or without primary cancer resection following recovery from preoperative neoadjuvant systemic chemotherapy.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Sotevtamab, FOLFOX
- Keywords
- Colorectal Cancer, Neoadjuvant Treatment, Liver Metastasis
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SotevtamabBiological
Also called AB-16B5
Sotevtamab is an inhibitor of the epithelial to mesenchymal transition. It is a fully humanized monoclonal antibody of IgG2 isotype against tumor-associated secreted clusterin (TA-sCLU)
FOLFOXCombination product
FOLFOX is a chemotherapy regimen for treatment of colorectal cancer, made up of the drugs folinic acid, fluorouracil, and oxaliplatin.
| Study group | Role | What they receive |
|---|---|---|
| Sotevtamab and FOLFOX | Experimental | Sotevtamab at 800 mg IV infusion once weekly on Days 1 and 8 for 6 cycles combined with FOLFOX (oxaliplatin 85 mg/m² IV infusion + leucovorin 400 mg/m² IV infusion + 5-Fluorouracil (5-FU) 400 mg/m² IV bolus + 5-FU 2400 mg/m² continuous IV infusion over 46 hours) once every 2 weeks on Day 1 for the first 4 cycles. Receives: Biological: Sotevtamab; Combination Product: FOLFOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rubbia-Brandt score at surgery
To characterize the pathological response of resected colorectal liver metastases as determined by the Rubbia-Brandt score. The Rubbia-Brandt score distinguishes five Tumor Regression Grades (TRG1-TRG5) according to the presence of residual tumor cells and extent of fibrosis.
Measured: 16-18 weeks
Treatment-Emergent Adverse Events
Incidence, relatedness, and severity of treatment-emergent adverse events
Measured: 14-16 weeks
Secondary outcomes (4)
Objective Response Rate (ORR)
To determine the objective response rate (ORR) per RECIST 1.1
Measured: 9-10 weeks
Quantity of circulating tumor DNA (ctDNA)
To evaluate minimal residual disease detection rate after colorectal liver metastases resection
Measured: Weeks 1 and 5, at surgery and post-surgery
Sotevtamab concentrations in plasma
To determine the pharmacokinetics (PK) of sotevtamab in the trial population
Measured: Weekly for 12 weeks and between Weeks 14 and 16
Presence of ADA
To evaluate the presence of anti-sotevtamab antibodies (ADA) in the trial population and their effect on exposure and tumor response
Measured: Weeks 1, 3, 8 and between Weeks 14 and 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2024
- Study start15 Feb 2024
- Primary completionMar 2026 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alethia Biotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06225843
- Sponsor's protocol ID
- AB-16B5-202
- Acronym
- EGIA-003
- Status last verified
- Feb 2025
- First submitted
- 17 Nov 2023
- Last updated
- 19 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof-of-Concept Phase II Trial to Evaluate the EMT Inhibitor Sotevtamab Combined With FOLFOX Administered as Neoadjuvant Treatment Prior to Resection of Colorectal Cancer Liver Metastasis
- ClinicalTrials.gov ID
- NCT06225843
- Acronym / sponsor ID
- EGIA-003 / AB-16B5-202
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Colorectal Cancer, Neoadjuvant Treatment, Liver Metastasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 17 participants (estimated)
- Lead sponsor
- Alethia BiotherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 15 Feb 2024 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 26 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase II study will recruit 17 colorectal cancer patients with liver-dominant metastases. All recruited patients will receive Sotevtamab at a dose of 800 mg once weekly for 6 cycles combined with FOLFOX once every 2 weeks for the first 4 cycles followed by liver metastases resection surgery with or without primary cancer resection. One cycle of treatment will consist of 14 days (2 weeks).
Detailed description
This is an open-label, single-arm, single-center proof-of-concept Phase II trial of sotevtamab in combination with FOLFOX-based preoperative neoadjuvant systemic chemotherapy in participants with resectable liver-dominant metastases and candidate to neoadjuvant FOLFOX followed by partial hepatectomy. Approximately 17 participants will be enrolled in this trial and will receive 4 cycles of FOLFOX (Cycle 1 to Cycle 4) as preoperative systemic chemotherapy and 6 cycles of sotevtamab (Cycle 1 to Cycle 6). One cycle of treatment will consist of 14 days (2 weeks). Sotevtamab will be administered by intravenous (IV) infusion at 800 mg on Day 1 and Day 8 of each cycle. FOLFOX will be administered on Day 1 of Cycle 1 to Cycle 4 as follows: oxaliplatin 85 mg/m² IV infusion + leucovorin 400 mg/m² IV infusion + 5-Fluorouracil (5-FU) 400 mg/m² IV bolus + 5-FU 2400 mg/m² continuous IV infusion over 46 hours. Participants will undergo liver metastasis resection with or without primary cancer resection following recovery from preoperative neoadjuvant systemic chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sotevtamab and FOLFOX | Experimental | Biological: Sotevtamab, Combination Product: FOLFOXSotevtamab at 800 mg IV infusion once weekly on Days 1 and 8 for 6 cycles combined with FOLFOX (oxaliplatin 85 mg/m² IV infusion + leucovorin 400 mg/m² IV infusion + 5-Fluorouracil (5-FU) 400 mg/m² IV bolus + 5-FU 2400 mg/m² continuous IV infusion over 46 hours) once every 2 weeks on Day 1 for the first 4 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Participants (male or non-pregnant female) must be ≥ 18 years of age on the day of signing the informed consent.
- Participants with stage IV colon or rectal adenocarcinoma with resectable liver-dominant metastases and candidate to neoadjuvant FOLFOX followed by partial hepatectomy.
- Participants may have had resection of their primary colon or rectal adenocarcinoma in the past or will have their primary cancer resected at the same time as the liver metastases resection or after liver metastases resection.
- Participants must not have received prior chemotherapy for metastatic disease. Prior adjuvant chemotherapy and radiotherapy following resection of primary tumor is acceptable if completed at least 12 months prior to trial enrolment.
- For multiple liver metastases, participants may undergo liver metastases needle-ablation of some metastases combined with surgical resection of others, as long as at least one metastasis is surgically resected.
Key exclusion criteria (19 listed)
- Participants who have received prior therapy with sotevtamab
- Concurrent administration of anti-VGFR, anti-EGFR, anti-VEGF or other biological or targeted therapy with neoadjuvant FOLFOX
- Participants with MMR-deficient primary colorectal tumor
- Hereditary colorectal cancer (e.g., familial colonic polyposis or Lynch syndrome)
- Participants who have another malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer.
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 |
|---|---|---|
| SotevtamabAlso: AB-16B5Sotevtamab is an inhibitor of the epithelial to mesenchymal transition. It is a fully humanized monoclonal antibody of IgG2 isotype against tumor-associated secreted clusterin (TA-sCLU) | Biological | Sotevtamab and FOLFOX |
| FOLFOXFOLFOX is a chemotherapy regimen for treatment of colorectal cancer, made up of the drugs folinic acid, fluorouracil, and oxaliplatin. | Combination product | Sotevtamab and FOLFOX |
Primary outcome
Rubbia-Brandt score at surgery
Time frame: 16-18 weeks
To characterize the pathological response of resected colorectal liver metastases as determined by the Rubbia-Brandt score. The Rubbia-Brandt score distinguishes five Tumor Regression Grades (TRG1-TRG5) according to the presence of residual tumor cells and extent of fibrosis.
Treatment-Emergent Adverse Events
Time frame: 14-16 weeks
Incidence, relatedness, and severity of treatment-emergent adverse events
4 secondary outcomes
Objective Response Rate (ORR)
Time frame: 9-10 weeks
Quantity of circulating tumor DNA (ctDNA)
Time frame: Weeks 1 and 5, at surgery and post-surgery
Sotevtamab concentrations in plasma
Time frame: Weekly for 12 weeks and between Weeks 14 and 16
Presence of ADA
Time frame: Weeks 1, 3, 8 and between Weeks 14 and 16
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2025.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sotevtamab and FOLFOX in people with Metastatic Colorectal Cancer, run by Alethia Biotherapeutics at 1 site in Canada.
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 19 inclusion and 19 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: looking for participants now, as of the sponsor's last update on 19 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Julie Laurin, B. Pharm, Ph.D. (514-581-8125, julie.laurin@alethiabio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rubbia-Brandt score at surgery (time frame: 16-18 weeks). The study lists 2 primary outcomes in all. 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 19 Feb 2025.