Clinical trial NCT05498597: AMT-151 in Patients With Selected Advanced Solid Tumours
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: 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
Keywords: Carcinoma
Cancer
Antibody-Drug Conjugate
Folate Receptor Alpha
Lead sponsor: Multitude Therapeutics Inc.
Sponsor class: INDUSTRY
Collaborators: name: Tigermed Consulting Co., Ltd
First posted: 2022-08-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Up to 24 months
measure: Maximum Tolerated Dose (MTD)
timeFrame: Up to 24 months
measure: Incidence of Adverse Events
timeFrame: Up to 24 months
Secondary outcomes:
measure: Overall Response Rate (ORR) according to the Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
timeFrame: Up to 24 months
measure: Disease Control Rate (DCR) according to the RECIST v1.1
timeFrame: Up to 24 months
measure: Progression-free Survival (PFS)
timeFrame: Up to 24 months
measure: Time to Treatment Response (TTR)
timeFrame: Up to 24 months
measure: Duration of Response (DoR)
timeFrame: Up to 24 months
measure: Overall Survival (OS)
timeFrame: Up to 24 months
measure: Concentration of anti-drug antibodies (ADA)
timeFrame: Up to 24 months
measure: Maximum observed concentration (C[max])
timeFrame: Up to 24 months
measure: Area under the curve (AUC)
timeFrame: Up to 24 months
measure: Terminal half-life (t[1/2])
timeFrame: Up to 24 months
measure: Time to maximum concentration (Tmax)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Brisbane
country: Australia
facility: ICON Cancer Centre
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Cancer Care Centre
state: Queensland
city: Adelaide
country: Australia
facility: Cancer Research SA
state: South Australia
city: Malvern
country: Australia
facility: Cabrini Malvern Hospital
state: Victoria
city: Perth
country: Australia
facility: One Clinical Research (OCR)
state: Western Australia
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
state: Fujian
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Shanghai
country: China
facility: Shanghai Tumor Hospital
state: Shanghai
Study officials:
affiliation: Cancer Research SA
name: Sarwan Bishnoi
role: PRINCIPAL_INVESTIGATOR
affiliation: Cabrini Malvern Hospital
name: Richardson Gary
role: PRINCIPAL_INVESTIGATOR
affiliation: Chris O'Brien Lifehouse
name: Steven Kao
role: PRINCIPAL_INVESTIGATOR
affiliation: Mater Cancer Care Centre
name: Catherine Shannon
role: PRINCIPAL_INVESTIGATOR
affiliation: ICON Cancer Centre
name: Jermaine Coward
role: PRINCIPAL_INVESTIGATOR
affiliation: One Clinical Research (OCR)
name: Mihitha Ariyapperuma
role: PRINCIPAL_INVESTIGATOR
References: