First-in-Human Trial of VBC106 in Participants With Advanced Solid Tumors

Official title

Phase 1/2a Open-Label Clinical Trial Evaluating VBC106, an FRα- and MSLN-Directed Bispecific Antibody Drug Conjugate, in Participants With Advanced Malignant Solid Tumors

Overview

This is a multicenter, open-label, multiple-dose, FIH Phase 1/2a trial. The Phase 1 portion adopts BOIN design to identify the MTD and/or RP2D with potential backfill cohorts. The Phase 2a portion consists of dose optimization followed by cohort expansion to confirm safety and tolerability and to further evaluate the efficacy of the selected RP2D in selected solid tumor malignancies for VBC106.

Interventions

• Drug VBC106
  VBC106

Primary outcome measures

• Incidence of dose-limiting toxicities (DLT) as defined in the protocol [Time frame: (DLT)From time of first dose of VBC106 to end of DLT period (approximately 21 days)]
• Incidence of Serious Adverse Events [Time frame: From time of Informed Consent to 30 days post last dose of VBC106]
• Incidence of Adverse Events (AEs) [Time frame: From time of Informed Consent to 30 days post last dose of VBC106]

Secondary outcome measures (11)

• Objective Response Rate (ORR) [Time frame: From date of first dose of VBC106 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)]
• Duration of Response (DoR) [Time frame: From date of first dose of VBC106 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years)]
• Disease Control Rate (DCR) at 12 weeks [Time frame: From date of first dose of VBC106 up until progression, or the last evaluable assessment in the absence of progression (for each patient this is expected to be measured at 12 weeks)]
• Progression free Survival (PFS) [Time frame: From date of first dose of VBC106 up until date of progression or death due to any cause (approximately 2 years)]
• Overall Survival (OS) [Time frame: From date of first dose of VBC106 up until the date of death due to any cause (approximately 2 years)]
• Pharmacokinetics of VBC106 [Time frame: From date of first dose of VBC106 up until 30 days post last dose]
• Pharmacokinetics of VBC106: Area under the concentration time curve (AUC) [Time frame: From date of first dose of VBC106 up until 30 days post last dose]
• Pharmacokinetics of VBC106: Maximum plasma concentration of the study drug (C-max) [Time frame: From date of first dose of VBC106 up until 30 days post last dose]
• Pharmacokinetics of VBC106: Time to maximum plasma concentration of the study drug (T-max) [Time frame: From date of first dose of VBC106 up until 30 days post last dose]
• Pharmacokinetics of VBC106: Half-life [Time frame: From date of first dose of VBC106 up until 30 days post last dose]
• Immunogenicity of VBC106: Anti-Drug Antibodies (ADA) [Time frame: From date of first dose of VBC106 up until 30 days post last dose]

Eligibility criteria

Inclusion criteria

• \- A participant must meet all of the following inclusion criteria to be eligible to participate in this trial:
• 1\. The participant or the participant's legally acceptable representative is willing and able to provide a written ICF before initiating any trial procedure.
• 2\. Histologically or cytologically confirmed unresectable advanced/metastatic solid tumor that has relapsed or progressed on or after standard systemic treatments, or is intolerable with standard treatment, or standard therapies are not appropriate or not safe in the opinion of the Investigator or refused by the participant.
• 3\. At least one measurable lesion as assessed according to RECIST v1.1 criteria for participants with non-pleural mesothelioma or other solid tumors and modified RECIST(mRECIST) for participants with malignant pleural mesothelioma.
• 4\. Male or female adults (defined as ≥ 18 years of age)
• 5\. ECOG performance status 0-1
• 6\. Has LVEF ≥ 50% by either ECHO or MUGA within 28 days before enrollment.
• 7\. Life expectancy greater than 12 weeks
• 8\. Archived tumor tissue sample available or able to undergo a fresh biopsy collection.
• 9\. Adequate organ and bone marrow function

Exclusion criteria

• Any unresolved toxicity of Grade ≥2 from previous anti-cancer treatment.
• Known or suspected brain metastases, or spinal cord compression.
• Has a medical history of interstitial lung diseases (e.g., non-infectious interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or current interstitial lung diseases or who are suspected to have these diseases by imaging at screening.
• Has a history of underlying pulmonary disorder including.
• History of chronic, active, or hereditary corneal disease.
• Participant history of congestive heart failure (CHF) Class II-IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment.

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

United States · 3 centers

• NEXT Oncology Houston — Houston
• START Mountain Region, LLC. — West Valley City
• NEXT Oncology Virginia — Fairfax

Australia · 1 center

• Icon Cancer Centre Wesley — Brisbane

Identifiers

NCT: NCT07686068 · VBC106-01-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗