AMT-676 in Patients With Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

Official title:

First-in-Human, Phase 1 Study of AMT-676 in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06400485
• Other study ID #: AMT-676-01
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: June 1, 2024
• Est. completion date: February 14, 2026

Study information

• Verified date: May 2024
• Source: Multitude Therapeutics Inc.
• Contact: Shuang Leng
• Phone: +61 411818616
• Email: shuang.leng[@]multitudetherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a first-in-human, non-randomized, open-label, multicenter Phase 1 study will evaluate the Maximum tolerated dose (MTD)/the recommended Phase 2 Dose (RP2D), safety, tolerability, anti-drug activity, pharmacokinetics, pharmacodynamics and immunogenicity of AMT-676 in Patients with Advanced Solid Tumors.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: February 14, 2026
• Est. primary completion date: October 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 12 weeks 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 12 weeks 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.

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• AMT-676
Participants will receive AMT-676 administered intravenously. Participants will be observed for first instance of dose limiting toxicities (DLT).

Locations

Country	Name	City	State
Australia	Gallipoli Medical Research Foundation	Greenslopes	Queensland
Australia	Macquarie University Hospital	Macquarie	New South wWales
Australia	Cabrini Hospital	Melbourne	Victoria
Australia	Linear Research	Nedlands	Western Australia
Australia	SCIENTIA Clinical Research Ltd	Randwick	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
Multitude Therapeutics Inc.

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Maximum Tolerated Dose (MTD)	The MTD will be determined using DLTs	30 days after the last dose of IMP
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Concentration of anti-drug antibodies (ADA)	Immunogenicity profile characterized by concentration of ADAs	30 days after the last dose of IMP
Secondary	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
Secondary	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
Secondary	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