AMT-151 in Patients With Selected Advanced Solid Tumours

Sponsor

Multitude Therapeutics Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05498597

Collaborator

Tigermed Consulting Co., Ltd (Industry)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumor Advanced Cancer Advanced Carcinoma Ovarian Cancer Ovarian Carcinoma Ovarian Epithelial Cancer Ovarian Endometrioid Adenocarcinoma Endometrial Cancer Endometrial Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Endometrioid Adenocarcinoma Endometrial Clear Cell Adenocarcinoma Lung Adenocarcinoma Triple Negative Breast Cancer Pancreatic Ductal Adenocarcinoma Malignant Pleural Mesothelioma Ovarian Clear Cell Carcinoma Ovarian Clear Cell Adenocarcinoma Ovarian Mucinous Adenocarcinoma	Drug: AMT-151	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Oct 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMT-151 Dose Escalation	Drug: AMT-151 Administered intravenously

Arm

Intervention/Treatment

Experimental: AMT-151 Dose Escalation

Drug: AMT-151

Administered intravenously

Outcome Measures

Primary Outcome Measures

Recommended Phase 2 Dose (RP2D) [Up to 24 months]
The RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data
Maximum Tolerated Dose (MTD) [Up to 24 months]
The MTD will be determined using DLTs
Incidence of Adverse Events [Up to 24 months]
Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v5.0

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Serous, endometrioid, clear-cell, or mucinous epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
Serous, endometrioid, or clear-cell endometrial cancer.
Adenocarcinoma of the lung.
Triple-negative breast cancer.
Pancreatic ductal adenocarcinoma.
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.