AMT-151 in Patients With Selected Advanced Solid Tumours

Ovarian Cancer Clinical Trial

Official title:

First-in-Human, Phase 1 Study of AMT-151, an Anti-Folate Receptor Alpha Antibody-Drug Conjugate, in Patients With Selected Advanced Solid Tumours

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05498597
• Other study ID #: AMT-151-01
• Status: Recruiting
• Phase: Phase 1
• Start date: January 25, 2023
• Est. completion date: October 30, 2024

Study information

• Verified date: October 2023
• Source: Multitude Therapeutics Inc.
• Contact: Jane Zhu
• Phone: 13917933915
• Email: juanjuan.zhu[@]multitudetherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This first-in-human study will evaluate the Maximum Tolerated Dose (MTD) / the Recommended Phase 2 Dose (RP2D), safety, tolerability, anti-tumor activity, pharmacokinetics, pharmacodynamics and immunogenicity of AMT-151, a novel antibody-drug conjugate against folate receptor alpha, in patients with selected advanced solid tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: October 30, 2024
• Est. primary completion date: January 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Patients must be willing and able to sign the Informed Consent Form, and to adhere to the study visit schedule and other protocol requirements.
• Age =18 years (at the time consent is obtained).
• Patients with the following histologically confirmed, advanced cancer diagnoses:

1. Serous, endometrioid, clear-cell, or mucinous epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.

2. Serous, endometrioid, or clear-cell endometrial cancer.

3. Adenocarcinoma of the lung.

4. Triple-negative breast cancer.

5. Pancreatic ductal adenocarcinoma.

6. Malignant pleural mesothelioma.

• Patients who have undergone any number of prior systemic therapies and have radiologically or clinically determined progressive disease during or after their most recent line of therapy, and for whom no further standard therapy is available, or who are intolerable to standard therapy.
• Patients must have at least one measurable or non-measurable lesion as per RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate function of bone marrow, liver, kidneys, heart.
• Both male and female patients must agree to use effective contraceptive methods.
• Women of child-bearing potential (WCBP) must have a negative serum pregnancy test.
• Availability of tumour tissue sample (either an archival specimen or a fresh biopsy material) at screening.

Key Exclusion Criteria:

• Prior treatment with any agent targeting Folate Receptor Alpha.
• Active central nervous system metastasis.
• Persistent toxicities from previous systemic anti-neoplastic treatments of Grade >1.
• Systemic anti-neoplastic therapy within five half-lives or 21 days, whichever is shorter, prior to the first dose of the study drug.
• Radiotherapy to lung field at a total radiation dose of >= 20 Gy within 6 months, wide-field radiotherapy (>30% of marrow-bearing bones) within 28 days, or focal radiation for analgesic purpose or for lytic lesions at risk of fracture within 14 days prior to the first dose of the study drug, or no recovery from side effects of such intervention.
• Major surgery (not including placement of vascular access device or tumor biopsies) within 28 days prior to the first dose of the study drug, or no recovery from side effects of such intervention.
• Prior allogeneic or autologous bone marrow transplantation.
• Significant cardiac or lung disease, active or chronic ocular disorders, thromboembolic or cerebrovascular events within 6 months prior to the first dose of the study drug, acute and/or clinically significant bacterial, fungal, or viral infection.
• Pregnant or breast-feeding females. Note: Other protocol defined Inclusion/Exclusion criteria apply.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Adenocarcinoma, Mucinous
• Advanced Cancer
• Advanced Carcinoma
• Advanced Solid Tumor
• Carcinoma
• Carcinoma, Endometrioid
• Carcinoma, Ovarian Epithelial
• Cystadenocarcinoma
• Endometrial Adenocarcinoma
• Endometrial Cancer
• Endometrial Clear Cell Adenocarcinoma
• Endometrial Endometrioid Adenocarcinoma
• Endometrial Neoplasms
• Endometrial Serous Adenocarcinoma
• Lung Adenocarcinoma
• Malignant Pleural Mesothelioma
• Mesothelioma
• Mesothelioma, Malignant
• Ovarian Cancer
• Ovarian Carcinoma
• Ovarian Clear Cell Adenocarcinoma
• Ovarian Clear Cell Carcinoma
• Ovarian Endometrioid Adenocarcinoma
• Ovarian Epithelial Cancer
• Ovarian Mucinous Adenocarcinoma
• Pancreatic Ductal Adenocarcinoma
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• AMT-151
Administered intravenously

Locations

Country	Name	City	State
Australia	Cancer Research SA	Adelaide	South Australia
Australia	ICON Cancer Centre	Brisbane	Queensland
Australia	Cabrini Malvern Hospital	Malvern	Victoria
Australia	One Clinical Research (OCR)	Perth	Western Australia
Australia	Mater Cancer Care Centre	South Brisbane	Queensland
Australia	Chris O'Brien Lifehouse	Sydney	New South Wales
China	Hunan Cancer Hospital	Changsha	Hunan
China	Fujian Provincial Cancer Hospital	Fuzhou	Fujian
China	Shanghai Tumor Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Multitude Therapeutics Inc.	Tigermed Consulting Co., Ltd

Countries where clinical trial is conducted

Australia,  China, 

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	Up to 24 months
Primary	Maximum Tolerated Dose (MTD)	The MTD will be determined using DLTs	Up to 24 months
Primary	Incidence of Adverse Events	Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v5.0	Up to 24 months
Secondary	Overall Response Rate (ORR) according to the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1	Proportion of patients achieving Complete Response (CR) or Partial Response (PR)	Up to 24 months
Secondary	Disease Control Rate (DCR) according to the RECIST v1.1	Proportion of patients achieving CR, PR or Stable Disease (SD)	Up to 24 months
Secondary	Progression-free Survival (PFS)	Time from date of start of treatment to date of the first progression or death, whichever occurs first.	Up to 24 months
Secondary	Time to Treatment Response (TTR)	Time from date of start of treatment to date of the first assessment of response (PR or CR)	Up to 24 months
Secondary	Duration of Response (DoR)	Time from date of first assessment of response (CR or PR) to date of the first progression or death, whichever occurs first	Up to 24 months
Secondary	Overall Survival (OS)	Time from date of start of treatment to date of death	Up to 24 months
Secondary	Concentration of anti-drug antibodies (ADA)	Immunogenicity profile characterized by concentration of ADAs	Up to 24 months
Secondary	Maximum observed concentration (C[max])	Pharmacokinetic profile characterized by the maximum observed concentration (C[max]) of AMT-151	Up to 24 months
Secondary	Area under the curve (AUC)	Pharmacokinetic profile characterized by the area under the curve (AUC) of AMT-151	Up to 24 months
Secondary	Terminal half-life (t[1/2])	Pharmacokinetic profile characterized by the terminal half-life (t[1/2]) of AMT-151	Up to 24 months
Secondary	Time to maximum concentration (Tmax)	Pharmacokinetic profile characterized by the time to maximum concentration (Tmax) of AMT-151	Up to 24 months