AMT-151 in Patients With Selected Advanced Solid Tumours

Study Overview
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Brief Summary
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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.

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

Conditions
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Ovarian Clear Cell Adenocarcinoma, Ovarian Mucinous Adenocarcinoma, 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

Intervention / Treatment
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* Drug: AMT-151


Participation Criteria
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Eligibility Criteria
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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. Note: Other protocol defined Inclusion/Exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMT-151 Dose Escalation<br> | Drug: AMT-151<br>* Administered intravenously<br>|

What is the study measuring?
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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 | Up to 24 months | 
| Maximum Tolerated Dose (MTD) | The MTD will be determined using DLTs | Up to 24 months | 
| Incidence of Adverse Events | Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v5.0 | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Disease Control Rate (DCR) according to the RECIST v1.1 | Proportion of patients achieving CR, PR or Stable Disease (SD) | Up to 24 months | 
| 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 | 
| 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 | 
| 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 | 
| Overall Survival (OS) | Time from date of start of treatment to date of death | Up to 24 months | 
| Concentration of anti-drug antibodies (ADA) | Immunogenicity profile characterized by concentration of ADAs | Up to 24 months | 
| Maximum observed concentration (C[max]) | Pharmacokinetic profile characterized by the maximum observed concentration (C[max]) of AMT-151 | Up to 24 months | 
| Area under the curve (AUC) | Pharmacokinetic profile characterized by the area under the curve (AUC) of AMT-151 | Up to 24 months | 
| Terminal half-life (t[1/2]) | Pharmacokinetic profile characterized by the terminal half-life (t[1/2]) of AMT-151 | Up to 24 months | 
| Time to maximum concentration (Tmax) | Pharmacokinetic profile characterized by the time to maximum concentration (Tmax) of AMT-151 | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carcinoma, Cancer, Antibody-Drug Conjugate, Folate Receptor Alpha