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

Overview

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

Interventions

• Drug AMT-116
  Administered intravenously

Primary outcome measures

• Recommended Phase 2 Dose (RP2D) [Time frame: Up to 24 months]
• Maximum Tolerated Dose (MTD) [Time frame: Up to 24 months]
• Type, incidence and severity of Adverse Events [Time frame: Up to 24 months]

Secondary outcome measures (8)

• Overall Response Rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [Time frame: Up to 24 months]
• Disease Control Rate (DCR) according to the RECIST v1.1 [Time frame: Up to 24 months]
• Progression-free Survival (PFS) [Time frame: Up to 24 months]
• Concentration of anti-drug antibodies (ADA) [Time frame: Up to 24 months]
• Maximum observed concentration (C[max]) [Time frame: Up to 24 months]
• Area under the curve (AUC) [Time frame: Up to 24 months]
• Terminal half-life (t[1/2]) [Time frame: Up to 24 months]
• Time to maximum concentration (Tmax) [Time frame: Up to 24 months]

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 6 centers

• Macquarie University Hospital — Sydney
• ICON Cancer Centre — Brisbane
• Southern Oncology Clinical Research Unit — Adelaide
• Alfred Hospital — Victoria Park
• Austin Health — Victoria Park
• Cabrini Hospital — Victoria Park

United States · 2 centers

• Sarah Cannon Research Institute — Denver
• Mary Crowley Cancer Research Centers — Dallas

American Samoa · 2 centers

• University of California San Francisco Cancer Center — San Francisco
• Carolina BioOncology Institute, LLC — Cary

Identifiers

NCT: NCT05725291 · AMT-116-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗