A Phase II Study of AMT-676 Combination Therapies in Advanced Colorectal Cancer

NCT07474727 | Not Yet Recruiting Phase 2

• 1 other identifier: AMT-676-201
• Study Type: interventional
• Target: 180
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is an open, multi-center, phase II study, aiming to evaluate the safety, tolerability and efficacy of AMT-676 combined with 5-fluorouracil, leucovorin, bevacizumab (or cetuximab) in participants with advanced colorectal cancer, and to assess the PK(Pharmacokinetic) characteristics and immunogenicity of AMT-676.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (5)

• AE & SAE

  Type, incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  30 days after the last treatment

• MTD

  Maximum Tolerated Dose will be determined by DLTs

  28 days after first dose

• DLTs

  Incidence of dose limiting toxicities

  28 days after first dose

• ORR

  Overall response rate

  through study completion, an average of 18 months

• PFS

  Progression-free survival

  through study completion, an average of 18 months

Secondary Outcomes (5)

• Cmax

  From first dose to end of treatment, an average of 1 year

• Ctrough

  From first dose to end of treatment, an average of 1 year

• AUC

  From first dose to end of treatment, an average of 1 year

• Specification of anti-drug antibodies

  From first dose to end of treatment, an average of 1 year

• Quantification of anti-drug antibodies

  From first dose to end of treatment, an average of 1 year

Study Arms (3)

AMT-676(dose level 1)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable)

EXPERIMENTAL

Drug: AMT-676; Drug: 5-FU; Drug: Leucovorin; Drug: Bevacizumab; Drug: Cetuximab

AMT-676(dose level 2)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable)

EXPERIMENTAL

Drug: AMT-676; Drug: 5-FU; Drug: Leucovorin; Drug: Bevacizumab; Drug: Cetuximab

oxaliplatin/irinotecan+5-FU+ leucovorin +bevacizumab (or cetuximab)

EXPERIMENTAL

Drug: 5-FU; Drug: Leucovorin; Drug: Bevacizumab; Drug: Cetuximab; Drug: Irinotecan; Drug: Oxaliplatin

Interventions

AMT-676 DRUG

Patients will get different dose levels treatment of AMT-676. AMT-676 will be Administered as an intravenous (IV) infusion every 2 weeks (Q2W) or every 4 weeks (Q4W).

AMT-676(dose level 1)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable); AMT-676(dose level 2)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable)

5-FU DRUG

5-FU 400 mg/m\^2 IV bolus on day 1, followed by 1200 mg/m\^2/day x 2 days (total 2400 mg/m\^2 over 46-48 hours) IV continuous infusion, q2w

AMT-676(dose level 1)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable); AMT-676(dose level 2)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable); oxaliplatin/irinotecan+5-FU+ leucovorin +bevacizumab (or cetuximab)

Leucovorin DRUG

Leucovorin 400 mg/m\^2 IV day 1, q2w

AMT-676(dose level 1)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable); AMT-676(dose level 2)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable); oxaliplatin/irinotecan+5-FU+ leucovorin +bevacizumab (or cetuximab)

Bevacizumab DRUG

Bevacizumab 5 mg/kg IV, day 1

AMT-676(dose level 1)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable); AMT-676(dose level 2)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable); oxaliplatin/irinotecan+5-FU+ leucovorin +bevacizumab (or cetuximab)

Cetuximab DRUG

Cetuximab 500 mg/m\^2 IV over 2 hours, day 1, q2w

AMT-676(dose level 1)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable); AMT-676(dose level 2)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable); oxaliplatin/irinotecan+5-FU+ leucovorin +bevacizumab (or cetuximab)

Irinotecan DRUG

Irinotecan 180 mg/m\^2 IV, day 1

oxaliplatin/irinotecan+5-FU+ leucovorin +bevacizumab (or cetuximab)

Oxaliplatin DRUG

Oxaliplatin 85 mg/m\^2 IV, day 1

oxaliplatin/irinotecan+5-FU+ leucovorin +bevacizumab (or cetuximab)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be willing and able to sign the ICF, and to adhere to the study visit schedule and other protocol requirements
• Patients with pathologically confirmed, unresectable advanced colorectal adenocarcinoma
• Patients must have at least one measurable lesion as per RECIST version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Life expectancy ≥6 months
• Patients must have adequate organ function
• Male and female individuals with child bearing potential must agree to take effective contraceptive measures from the moment they sign the informed consent form until 6 months after the last administration of the study drug
• WCBP(Women of Child-Bearing Potential) must have a negative serum pregnancy test within 7 days prior to first dose of the IMP
• Male patients must agree not to donate sperm, and female patients must agree not to donate eggs, while on study treatment and for at least 3 months and 6 months, respectively, after the last dose of the IMP(Investigational Medicinal Product)
• Availability of tumor tissue sample

You may not qualify if:

• Prior treatment with any same target
• Systemic anti-neoplastic therapy within five half-lives or 21 days, whichever is shorter, prior to first dose of the IMP
• Persistent toxicities from previous systemic anti-neoplastic treatments of Grade \>1
• Major surgery within 28 days prior to first dose of the IMP, or no recovery from side effects of such intervention, or a surgery is planned to be conducted within the expected participation period of the trial or within 4 weeks after the last administration of the drug
• History of thromboembolic or cerebrovascular events during last 6 mouths
• During the three months prior to the first administration of the drug, there were any life-threatening bleeding events, or grade 3 or higher gastrointestinal/venous variceal bleeding events that required blood transfusion, endoscopy, or surgical treatment. Or there were other diseases that the researchers believed posed a higher risk of bleeding or thrombosis during the study period
• Has a history of interstitial lung disease (ILD)/pneumonitis that required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis , or other lung disease significantly impacting lung function at baseline.
• Any other concurrent diseases or conditions that could affect the research judgment or impede the completion of the research procedures and follow-up checks
• Central nervous system (CNS) metastasis
• Have a history of active or acute diverticulitis, abdominal abscess, gastrointestinal obstruction, fistula, or peritoneal cancer
• Any evidence indicates severe or uncontrolled systemic diseases
• Acute and/or clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV).
• Administration of a live vaccine within 28 days prior to the administration of the first dose of the IMP
• Patients requiring concurrent treatment of strong/moderate inhibitors or strong inducers of cytochrome P450 3A4 or 1A2 enzyme (CYP3A or CYP1A2) within 2 weeks prior to the first dose and during the study treatment
• Known or suspected severe allergy/hypersensitivity (resulting in treatment discontinuation) to monoclonal antibodies

Sponsors & Collaborators

• Multitude Therapeutics Inc.: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Leucovorin; Bevacizumab; Cetuximab; Irinotecan; Oxaliplatin

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

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Coordination Complexes; Organic Chemicals

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: March 5, 2026
• First Posted: March 16, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): February 28, 2028
• Last Updated: March 16, 2026

Record last verified: 2026-03