AMT-151 in Patients With Selected Advanced Solid Tumours

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor; Pancreatic Ductal Adenocarcinoma; Endometrial Adenocarcinoma; Endometrial Serous Adenocarcinoma; Lung Adenocarcinoma; Advanced Cancer; Advanced Carcinoma; Ovarian Cancer; Ovarian Carcinoma; Endometrial Clear Cell Adenocarcinoma
• Interventions: Drug: AMT-151

• Registration Number: NCT05498597
• Lead Sponsor: Multitude Therapeutics Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-08-10
• Study First Submitted QC: 2022-08-10
• Study First Posted: 2022-08-12
• Study Start: 2023-01-25
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-17
• Last Update Posted: 2023-10-19
• Primary Completion: 2024-01-01
• Study Completion: 2024-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AMT-151 Dose Escalation	AMT-151	-

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse Events	Up to 24 months	Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v5.0
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

Secondary Outcome Measures

Name	Time	Method
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)
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)
Concentration of anti-drug antibodies (ADA)	Up to 24 months	Immunogenicity profile characterized by concentration of ADAs
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.
Maximum observed concentration (C[max])	Up to 24 months	Pharmacokinetic profile characterized by the maximum observed concentration (C\[max\]) 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
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
Area under the curve (AUC)	Up to 24 months	Pharmacokinetic profile characterized by the area under the curve (AUC) 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

Trial Locations

Locations (9)

Chris O'Brien Lifehouse; 🇦🇺 Sydney, New South Wales, Australia

Cancer Research SA; 🇦🇺 Adelaide, South Australia, Australia

One Clinical Research (OCR); 🇦🇺 Perth, Western Australia, Australia

Shanghai Tumor Hospital; 🇨🇳 Shanghai, Shanghai, China

Mater Cancer Care Centre; 🇦🇺 South Brisbane, Queensland, Australia

Cabrini Malvern Hospital; 🇦🇺 Malvern, Victoria, Australia

ICON Cancer Centre; 🇦🇺 Brisbane, Queensland, Australia

Fujian Provincial Cancer Hospital; 🇨🇳 Fuzhou, Fujian, China

Hunan Cancer Hospital; 🇨🇳 Changsha, Hunan, China