AMT-676 in Patients With Advanced Solid Tumors

First-in-Human, Phase I/II Study of AMT-676, an Anti CDH17 Antibody-Drug Conjugate, in Patients With Advanced Solid Tumors

This is a first-in-human, open-label, multicenter Phase Ia/Ib study of AMT- 676, followed by an open-label, multicenter, dose-escalation.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: AMT-676

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jane Zhu; Phone Number: +86 13917933915; Email: juanjuan.zhu@multitudetherapeutics.com

Study Locations

• American Samoa
  • North Carolina
    • Huntersville, North Carolina, American Samoa, 28078
      • Not yet recruiting
      • Carolina BioOncology Institute
      • Contact: Neel Gandhi; Phone Number: 9804411035; Email: ngandhi@carolinabiooncology.org
  • Pennsylvania
    • Philadelphia, Pennsylvania, American Samoa, 19107
      • Not yet recruiting
      • John Hopkins Sidney Kimmel Comprehensive Cancer Center
      • Contact: Daniel Lin; Phone Number: 2159556923; Email: Daniel.Lin@jefferson.edu
  • Texas
    • San Antonio, Texas, American Samoa
      • Not yet recruiting
      • South Texas Accelerated Research Therapeutics (START) San Antonio
      • Contact: Drew Rasco; Phone Number: 2105935232; Email: drew.rasco@startsa.com
• Australia
  • New South Wales
    • Randwick, New South Wales, Australia
      • Recruiting
      • Scientia Clinical Research Ltd
      • Contact: Charlotte Lemech; Email: charlotte.lemech@scientiaclinicalresearch.com
  • New South wWales
    • Macquarie, New South wWales, Australia
      • Recruiting
      • Macquarie University Hospital
  • Queensland
    • Greenslopes, Queensland, Australia
      • Recruiting
      • Gallipoli Medical Research Foundation
  • Victoria
    • Melbourne, Victoria, Australia
      • Recruiting
      • Cabrini Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia
      • Recruiting
      • Linear Research
• China
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Not yet recruiting
      • Fujian Provincial Cancer Hospital
      • Contact: Robo Lin
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Not yet recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Ruihua Xu
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Not yet recruiting
      • Shanghai East Hospital
      • Contact: Junli Xue
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Not yet recruiting
      • Sichuan Provincial People's Hospital
      • Contact: Hao Liu
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Not yet recruiting
      • Sir Run Run Shaw Hospital
      • Contact: Hongming Pan

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Patients must be willing and able to sign the ICF, and to adhere to the study visit Schedule and other protocol requirements.
2. Age ≥18 years (at the time consent is obtained).
3. Patients with pathologically confirmed unresectable advanced solid tumor. Preferred tumor types include colorectal cancer, gastric cancer, esophageal adenocarcinoma, cholangiocarcinoma, pancreatic ductal cancers, and neuroendocrine tumors.
4. Patients who have undergone at least one systemic therapy and have radiologically or clinically determined progressive disease during or after most recent line of therapy, and for whom no further standard therapy is available, or who are intolerable to standard therapy.
5. Patients must have at least one measurable lesion as per RECIST version 1.1.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
7. Life expectancy ≥3 months.
8. Patients must have adequate organ function
9. Women of child-bearing potential (WCBP) must have a negative serum pregnancy test.
10. Male patients must agree to use a latex condom, even if they had a successful vasectomy, while on study treatment and for at least 6months after the last dose of the IMP.
11. 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.
12. Availability of tumour tissue sample (either an archival specimen or a fresh biopsy material) at screening.

Key Exclusion Criteria:

1. Prior treatment with any agent for the same target or ADC based on topoisomerase I inhibitor.
2. Central nervous system (CNS) metastasis
3. History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.
4. Persistent toxicities from previous systemic anti-neoplastic treatments of Grade >1.
5. Systemic anti-neoplastic therapy within five half-lives or21 days, whichever is shorter, prior to first dose of the IMP.
6. Radiotherapy to lung field at a total radiation dose of ≥20 Gy within 6 months, wide-field radiotherapy (e.g., >30% of marrow-bearing bones) within 28 days.
7. Major surgery (not including placement of vascular access device or tumor biopsies) within 28 days prior to first dose of the IMP, or no recovery from side effects of such intervention.
8. Significant cardiac disease, such as recent (within months prior to first dose of the IMP) myocardial infarction or acute coronary syndromes (including unstable angina pectoris), congestive heart failure (New York Heart Association class III or IV), uncontrolled hypertension (SBP ≥ 160mmHg or DBP ≥ 100mmHg), uncontrolled cardiac arrhythmias.
9. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis (e.g., idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, etc.) or other lung disease significantly impacting lung function at baseline.
10. History of thromboembolic or cerebrovascular events, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis, or pulmonary emboli within six months prior to first dose of the IMP.
11. Acute and/or clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV)
12. Administration of a live vaccine within 28 days prior to the administration of the first dose of the IMP.
13. Patients requiring concurrent treatment of strong inhibitors or inducers of cytochrome P450 3A4 or 1A2 enzyme (CYP3A or CYP1A2) within 2 weeks prior to the first dose and during the study treatment.
14. Known or suspected severe allergy/hypersensitivity (resulting in treatment discontinuation) to monoclonal antibodies.
15. Known or suspected intolerance to the components of the IMP.
16. Concurrent participation in another investigational therapeutic clinical trial.
17. Patients with known active alcohol or drug abuse.
18. Pregnant or breast-feeding females
19. Mental or medical conditions that prevent the patient from giving informed consent or complying with the trial or other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with the study participation or the IMP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrolment in this study.
20. Prior history of malignancy other than inclusion diagnosis within five years prior to first dose of the IMP.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMT-676 Dose escalation; Drug- AMT-676 Dosage level: AMT-676 will be administered as an intravenous (IV) infusion. Dosage form: Vial Route of administration: Intravenous Infusion	Drug: AMT-676; Participants will receive AMT-676 administered intravenously. Participants will be observed for first instance of dose limiting toxicities (DLT).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose (RP2D)	The RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data	30 days after the last dose of IMP
Maximum Tolerated Dose (MTD)	The MTD will be determined using DLTs	30 days after the last dose of IMP
Type, incidence and severity of Adverse Events	Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v5.0	30 days after the last dose of IMP

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed concentration (C[max])	Pharmacokinetic profile characterized by the maximum observed concentration (C[max]) of AMT-676	30 days after the last dose of IMP
Time to maximum concentration (Tmax)	Pharmacokinetic profile characterized by the time to maximum concentration (Tmax) of AMT-676	30 days after the last dose of IMP
Area under the curve (AUC)	Pharmacokinetic profile characterized by the area under the curve (AUC) of AMT-676	30 days after the last dose of IMP
Terminal half-life (t[1/2])	Pharmacokinetic profile characterized by the terminal half-life (t[1/2]) of AMT-676	30 days after the last dose of IMP
Concentration of anti-drug antibodies (ADA)	Immunogenicity profile characterized by concentration of ADAs	30 days after the last dose of IMP
Overall Response Rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Proportion of patients achieving Complete Response (CR) or Partial Response (PR)	30 days after the last dose of IMP
Disease Control Rate (DCR) according to the RECIST v1.1	Proportion of patients achieving CR, PR or Stable Disease (SD)	30 days after the last dose of IMP
Progression-free Survival (PFS)	Time from date of start of treatment to date of the first progression or death, whichever occurs first	30 days after the last dose of IMP

Collaborators and Investigators

• Sponsor: Multitude Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2024
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 1, 2024
• First Submitted That Met QC Criteria: May 1, 2024
• First Posted (Actual): May 6, 2024

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: AMT-676-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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