AMT-116 in Patients with Solid Tumors

Phase 1/2 Study of AMT-116 in Patients with Advanced Solid Tumors

The purpose of this study is to evaluate the safety and efficacy of AMT-116 monotherapy in subjects with advanced solid tumors. The study is divided into two parts: the part I is dose escalation and the Part Ⅱ for expansion.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: AMT-116

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yixuan Wang; Phone Number: +86-021-33560023; Email: yixuan.wang@multitudetherapeutics.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China
      • Recruiting
      • Fujian Cancer Hospital
  • Guangdong
    • Dongguan, Guangdong, China
      • Not yet recruiting
      • Dongguan People's Hospital
    • Guangzhou, Guangdong, China
      • Recruiting
      • ZhuJiang Hospital of Southern Medical University（The Second Clinical Medical College）
  • Guangxi
    • Nanning, Guangxi, China
      • Recruiting
      • Guangxi Medical University Cancer Hospital
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • Hunan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Cancer Hospital
      • Contact: Zhengbo Song
    • Wenzhou, Zhejiang, China
      • Recruiting
      • The Second Affiliated Hospital and Yuying childrens Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

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

Description

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 histologically confirmed, unresectable advanced solid tumor. Preferred tumor types include non-small cell lung, head and neck, esophageal, cervical, breast, bladder, gastric, biliary tract, skin squamous cell, liver, and basal cell cancer.
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. The anticipated survival duration is no less than three months.
8. Patients must have adequate organ function
9. Women of child-bearing potential (WCBP) must consent to the use of two effective contraceptive methods during the study treatment period and for at least 12 weeks after the final administration of IMP
10. Women of child-bearing potential (WCBP) must have a negative serum pregnancy test within seven days preceding the initial administration of the investigational medicinal product (IMP).
11. Male patients must agree to use a latex condom, even if they had a successful vasectomy, while on study treatment and for at least 12 weeks after the last dose of the IMP.
12. 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 12 weeks after the last dose of the IMP.
13. Availability of tumour tissue sample (either an archival specimen or a fresh biopsy material) at screening.

Exclusion Criteria:

1. Prior therapy with ADC based on Top1 inhibitor.
2. Central nervous system (CNS) metastasis.
3. Active or chronic skin disorder requiring systemic therapy.
4. History of Steven's Johnson's syndrome or Toxic Epidermal Necrolysis syndrome.
5. Active ocular conditions requiring treatment or close monitoring, including, but not limited to: macular degeneration, papilledema, active diabetic retinopathy with macular oedema, wet age-related macular degeneration requiring intravitreal injections, or uncontrolled glaucoma.
6. Persistent toxicities from previous systemic anti-neoplastic treatments of Grade >1.
7. Systemic anti-neoplastic therapy within five half-lives or 21 days, whichever is shorter, prior to first dose of the IMP.
8. 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.
9. Major surgery (not including placement of vascular access device or tumor biopsies) within 28 days prior to the first dose of the IMP, or no recovery from side effects of such intervention.
10. Significant cardiac disease, such as recent (within six 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, uncontrolled cardiac arrhythmias.
11. 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.).
12. 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.
13. Acute and/or clinically significant bacterial, fungal or viral infection including hepatitis B virus (HBV), hepatitis C virus (HCV), and known human immunodeficiency virus (HIV).
14. Administration of a live vaccine within 28 days prior to the administration of the first dose of the IMP.
15. Patients requiring concurrent treatment of strong inhibitors or inducers of cytochrome P450 3A4 enzyme (CYP3A4) within 2 weeks prior to the first dose and during the study treatment.
16. Known or suspected severe allergy/hypersensitivity (resulting in treatment discontinuation) to monoclonal antibodies.
17. Known or suspected intolerance to the components of the IMP.
18. Concurrent participation in another investigational therapeutic clinical trial.
19. Patients with known active alcohol or drug abuse.
20. Pregnant or breast-feeding females.
21. Mental or medical disorders that prevent patients from signing informed consent or complying with the study, or other severe acute or chronic medical or psychiatric disorders or abnormal laboratory results that may increase the risk associated with study participation or IMP administration or may interfere with the interpretation of study results and, in the investigator's judgment, make patients ineligible for enrollment in the study.
22. There was a history of malignant tumors other than the selected diagnosis within 5 years prior to the first administration of IMP

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I: Dose escalation; Five dose levels in the Phase I part of the study	Drug: AMT-116; AMT-116 is an antibody Drug Conjugate (ADC)
Other: Phase II: Dose Expansion; Patients in phase II will be enrolled based on the RP2D (Recommended Phase 2 Dose) determined from phase I dose escalation data.	Drug: AMT-116; AMT-116 is an antibody Drug Conjugate (ADC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Maximum Tolerated Dose(MTD) and the Recommended Phase 2 Dose(RP2D) of AMT-116	The MTD（Maximum Tolerated Dose） and RP2D（Recommended Phase 2 Dose） will be determined for expansion using dose limiting toxicities (DLTs) and all other available study data	approximately 12 months
Phase I: Type, incidence and severity of Adverse Events,Dose Limiting Toxicities (DLTs)	Assess safety and tolerability of AMT-116 by the National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) version 5.0	approximately 12 months
Phase II: Objective Response Rate(ORR)	To evaluate the objective response rate (ORR) [Complete Response (CR) + Partial Response (PR)] according to the RECIST v1.1	approximately 18 months
Phase II: Type, incidence and severity of Adverse Events	Assess safety and tolerability of AMT-116 by the National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) version 5.0	approximately 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: 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)	approximately 12 months
Phase I Disease Control Rate (DCR) according to the RECIST v1.1	Proportion of patients achieving CR, PR or Stable Disease (SD)	approximately 12 months
Phase I: Progression-free Survival (PFS)	Time from date of start of treatment to date of the first progression or death, whichever occurs first	approximately 12 months
Phase I: Levels of target expression or Tumor Infiltrating Lymphocyte in tumor tissue	To assess levels of target expression and Tumor Infiltrating Lymphocyte in tumor tissue	approximately 12 months
Phase I: Concentration of anti-drug antibodies (ADA)	Immunogenicity profile characterized by concentration of ADAs	approximately 12 months
Phase I: Maximum observed concentration (C[max])	Pharmacokinetic profile characterized by the maximum observed concentration (C[max]) of AMT-116	approximately 12 months
Phase I: Area under the curve (AUC)	Pharmacokinetic profile characterized by the area under the curve (AUC) of AMT-116	approximately 12 months
Phase I: Terminal half-life (t[1/2])	Pharmacokinetic profile characterized by the terminal half-life (t[1/2]) of AMT-116	approximately 12 months
Phase I: Time to maximum concentration (Tmax)	Pharmacokinetic profile characterized by the time to maximum concentration (Tmax) of AMT-116	approximately 12 months
Phase II: Disease Control Rate (DCR) according to the RECIST v1.1	Proportion of patients achieving CR, PR or Stable Disease (SD)	approximately 18 months
Phase II: Progression-free Survival (PFS) according to RECIST v1.1	Time from date of start of treatment to date of the first progression or death, whichever occurs first.	approximately 18 months
Phase II: Duration of response (DOR)	DOR is defined as the time from the date of first documented CR or PR to PD or death due to any cause, whichever occurs first.	approximately 18 months
Phase II: Time to response(TTR)	The time from the start date of treatment to the date of the first response assessment (PR or CR)	approximately 18 months
Phase II: Levels of target expression in tumor tissue	To assess levels of target expression in tumor tissue and correlation of those levels with responses and toxicity.	approximately 18 months
Phase II: Percentage of patients with ADA formation to AMT-116.	To obtain Percentage of patients with ADA formation to AMT-116	approximately 18 months
Phase II: Maximum observed concentration (C[max])	To characterize the PK profile of AMT-116 by analyzing maximum observed concentration (C[max]) of the ADC, total antibody, and free payload.	approximately 18 months
Phase II: Area under the curve (AUC)	To characterize the PK profile of AMT-116 by analyzing area under the curve (AUC) of the ADC, total antibody, and free payload.	approximately 18 months
Phase II: Terminal half-life (t[1/2])	To characterize the PK profile of AMT-116 by analyzing the pharmacokinetic parameter Terminal half-life (t½ )of the ADC, total antibody, and free payload.	approximately 18 months
Phase II: Time to maximum concentration (Tmax)	To characterize the PK profile of AMT-116 by analyzing the pharmacokinetic parameter time to maximum concentration (Tmax) of the ADC, total antibody, and free payload.	approximately 18 months

Collaborators and Investigators

• Sponsor: Multitude Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: AMT-116-02

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No