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

An Phase II Study Evaluating the Safety and Efficacy of AMT-676 in Combination With 5-fluorouracil, Leucovorin, Bevacizumab (or Cetuximab) in Participants of Advanced Colorectal Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: AMT-676; Drug: 5-FU; Drug: Leucovorin; Drug: Bevacizumab; Drug: Cetuximab; Drug: Irinotecan; Drug: Oxaliplatin

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Known or suspected intolerance to the components of the IMP
• Concurrent participation in another investigational therapeutic clinical trial
• Pregnant or breast-feeding females
• Investigator determined that the trial participants who were not suitable to participate in this study for other reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMT-676(dose level 1)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable)	Drug: AMT-676; 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).; Drug: 5-FU; 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; Drug: Leucovorin; Leucovorin 400 mg/m^2 IV day 1, q2w; Drug: Bevacizumab; Bevacizumab 5 mg/kg IV, day 1; Drug: Cetuximab; Cetuximab 500 mg/m^2 IV over 2 hours, day 1, q2w
Experimental: AMT-676(dose level 2)+5-FU+Leucovorin+Bevacizumab or Cetuximab(if applicable)	Drug: AMT-676; 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).; Drug: 5-FU; 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; Drug: Leucovorin; Leucovorin 400 mg/m^2 IV day 1, q2w; Drug: Bevacizumab; Bevacizumab 5 mg/kg IV, day 1; Drug: Cetuximab; Cetuximab 500 mg/m^2 IV over 2 hours, day 1, q2w
Experimental: oxaliplatin/irinotecan+5-FU+ leucovorin +bevacizumab (or cetuximab)	Drug: 5-FU; 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; Drug: Leucovorin; Leucovorin 400 mg/m^2 IV day 1, q2w; Drug: Bevacizumab; Bevacizumab 5 mg/kg IV, day 1; Drug: Cetuximab; Cetuximab 500 mg/m^2 IV over 2 hours, day 1, q2w; Drug: Irinotecan; Irinotecan 180 mg/m^2 IV, day 1; Drug: Oxaliplatin; Oxaliplatin 85 mg/m^2 IV, day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	maximum concentration of the ADC, total antibody and free payload	From first dose to end of treatment, an average of 1 year
Ctrough	predose concentration of the ADC, total antibody and free payload	From first dose to end of treatment, an average of 1 year
AUC	Area Under the Curve of the ADC, total antibody and free payload	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

Collaborators and Investigators

• Sponsor: Multitude Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: March 5, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Bevacizumab; Irinotecan; Cetuximab; Fluorouracil; Leucovorin
• Other Study ID Numbers: AMT-676-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No