Sotevtamab (AB-16B5) Combined With FOLFOX as Neoadjuvant Treatment Prior to Resection of Colorectal Cancer Liver Metastasis

NCT06225843 | Recruiting Phase 2 FDA Drug

• 1 other identifier: AB-16B5-202
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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 primary cancer resection. One cycle of treatment will consist of 14 days (2 weeks).

Conditions

Metastatic Colorectal Cancer

Keywords

Colorectal Cancer; Neoadjuvant Treatment; Liver Metastasis

Outcome Measures

Primary Outcomes (2)

• 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.

  16-18 weeks

• Treatment-Emergent Adverse Events

  Incidence, relatedness, and severity of treatment-emergent adverse events

  14-16 weeks

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  9-10 weeks

• Quantity of circulating tumor DNA (ctDNA)

  Weeks 1 and 5, at surgery and post-surgery

• Sotevtamab concentrations in plasma

  Weekly for 12 weeks and between Weeks 14 and 16

• Presence of ADA

  Weeks 1, 3, 8 and between Weeks 14 and 16

Study Arms (1)

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.

Biological: Sotevtamab; Combination Product: FOLFOX

Interventions

Sotevtamab BIOLOGICAL

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)

Also known as: AB-16B5

Sotevtamab and FOLFOX

FOLFOX COMBINATION_PRODUCT

FOLFOX is a chemotherapy regimen for treatment of colorectal cancer, made up of the drugs folinic acid, fluorouracil, and oxaliplatin.

Sotevtamab and FOLFOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:
• i. ≥ 45 years of age and has not had menses for more than 2 years

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Alethia Biotherapeutics: lead

Study Sites (1)

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Folfox protocol

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

Central Study Contacts

Julie Laurin, B. Pharm, Ph.D.

CONTACT

514-581-8125; julie.laurin@alethiabio.com

Study Design

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

Study Record Dates

• First Submitted: November 17, 2023
• First Posted: January 26, 2024
• Study Start: February 15, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 19, 2025

Record last verified: 2025-02

Locations

CA (1)