Clinical trial NCT05725291: AMT-116 in Patients With Advanced Solid Tumors
Official title: First-in-Human, Phase 1 Study of AMT-116 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Multitude Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-13
Enrollment: 80
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-116, in Patients with Advanced Solid Tumors


Eligibility criteria: Key Inclusion Criteria:

* Patients must be willing and able to sign the ICF, and to adhere to the study visit schedule and other protocol requirements.
* Age ≥18 years (at the time consent is obtained).
* Patients with histologically confirmed, unresectable advanced solid tumor. Preferred tumor types include head and neck, non-small cell lung, esophageal, pancreatic, large cell lung, colorectal, cervical, breast, bladder, gastric, biliary tract, skin squamous cell, liver, and basal cell cancer.
* Patients who have undergone at least one systemic therapy and have radiologically or clinically determined progressive disease during or after 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 lesion as per RECIST version 1.1.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* Both male and female patients must agree to use effective contraceptive methods.
* Patients must have adequate organ function.
* Women of child-bearing potential (WCBP) must have a negative serum pregnancy test.
* Male patients must agree to use a latex condom, even if they had a successful vasectomy, while on study treatment and for at least 12 weeks after the last dose of the IMP.
* Male patients must agree not to donate sperm, and female patients must agree not to donate eggs, while on study treatment and for at least 12 weeks after the last dose of the IMP.
* Availability of tumour tissue sample (either an archival specimen or a fresh biopsy material) at screening.

Key Exclusion Criteria:

* Prior therapy with ADC based on Top1 inhibitor.
* Central nervous system (CNS) metastasis.
* Active or chronic skin disorder requiring systemic therapy.
* History of Steven's Johnson's syndrome or Toxic Epidermal Necrolysis syndrome.
* Active ocular conditions requiring treatment or close monitoring, including, but not limited to: macular degeneration, papilledema, active diabetic retinopathy with macular oedema, wet age-related macular degeneration requiring intravitreal injections, or uncontrolled glaucoma.
* 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 first dose of the IMP.
* Radiotherapy to lung field at a total radiation dose of ≥20 Gy within 6 months, wide-field radiotherapy (e.g., \> 30% of marrow-bearing bones) within 28 days.
* Major surgery (not including placement of vascular access device or tumor biopsies) within 28 days prior to the first dose of the IMP, or no recovery from side effects of such intervention.
* Prior allogeneic or autologous bone marrow transplantation.
* Significant cardiac disease, such as recent (within six months prior to first dose of the IMP) myocardial infarction or acute coronary syndromes (including unstable angina pectoris), congestive heart failure (New York Heart Association class III or IV), uncontrolled hypertension, uncontrolled cardiac arrhythmias.
* 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: Type, incidence and severity of Adverse Events
timeFrame: Up to 24 months
Secondary outcomes:
measure: Overall Response Rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (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: 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: Denver
country: United States
facility: Sarah Cannon Research Institute
state: Colorado
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Centers
state: Texas
city: Cary
country: American Samoa
facility: Carolina BioOncology Institute, LLC
city: San Francisco
country: American Samoa
facility: University of California San Francisco Cancer Center
city: Syd
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: ICON Cancer Centre
state: Queensland
city: Adelaide
country: Australia
facility: Southern Oncology Clinical Research Unit
state: South Australia
city: Victoria Park
country: Australia
facility: Alfred Hospital
state: Victoria
city: Victoria Park
country: Australia
facility: Austin Health
state: Victoria
city: Victoria Park
country: Australia
facility: Cabrini Hospital
state: Victoria
Study officials:
affiliation: ICON Cancer Centre
name: Jermaine Coward
role: PRINCIPAL_INVESTIGATOR
References: