A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-130850 in Participants With Advanced Solid and Hematologic Tumors
- Conditions
- Advanced Solid TumorsAdvanced Hematologic Tumors
- Interventions
- Registration Number
- NCT06188208
- Lead Sponsor
- Vividion Therapeutics, Inc.
- Brief Summary
A FIH study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VVD-130850, as single agent and in combination with checkpoint inhibition, in participants with advanced solid and hematologic tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 280
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Histologically or cytologically confirmed metastatic or unresectable solid tumor or advanced non-Hodgkin's lymphoma (NHL).
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Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
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Adequate organ and bone marrow function as defined in the protocol.
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For Combination Therapy Expansion:
- Serine/threonine kinase 11/ liver kinase B1 (STK11/LKB1) mutated non-small cell lung cancer (NSCLC) as assessed by historical (local) test.
- Must be refractory to or have progressed on or after a platinum-based doublet regimen and an immune checkpoint inhibitor (CPI). These therapies could have been given in the same line of therapy or different lines of therapy.
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Measurable disease by RECIST version 1.1 as assessed by the Investigator.
Key
-
Have a diagnosis of immunodeficiency or are receiving systematic steroid therapy or any other form of immunosuppressive therapy.
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Prior allogeneic transplantation.
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History of cardiac diseases as defined in detail in the protocol.
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Clinically significant infection or any eye infection.
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Active central nervous system (CNS) malignancies (previously treated CNS malignancies are not exclusionary).
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Combination Therapy Expansion:
- Known hypersensitivity or contraindication to pembrolizumab or any of its components.
- Any prior toxicity (Grade 3 or 4) related to immunotherapy leading to treatment discontinuation with the exception of the history of immunotherapy-related endocrinopathy controlled with ongoing medical management (e.g., hypothyroidism, adrenal insufficiency, diabetes).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation: VVD-130850 + Pembrolizumab Combination Therapy Pembrolizumab Participants will receive ascending doses of VVD-130850, orally, once daily, along with pembrolizumab intravenous (IV) infusion, every 3 weeks (Q3W) in 21-day treatment cycles during the dose escalation phase. Dose Escalation: VVD-130850 Single Agent VVD-130850 Participants will receive ascending doses of VVD-130850, orally, once daily in 21-day treatment cycles during the dose escalation phase. Dose Expansion: VVD-130850 + Pembrolizumab Combination Therapy VVD-130850 Participants will receive VVD-130850 at RDE orally, once daily along with pembrolizumab IV infusion, Q3W in 21-day treatment cycles during the dose expansion phase. Dose Escalation: VVD-130850 + Pembrolizumab Combination Therapy VVD-130850 Participants will receive ascending doses of VVD-130850, orally, once daily, along with pembrolizumab intravenous (IV) infusion, every 3 weeks (Q3W) in 21-day treatment cycles during the dose escalation phase. Dose Expansion: VVD-130850 Single Agent VVD-130850 Participants will receive VVD-130850 at recommended dose for expansion (RDE), orally, once daily in 21-day treatment cycles during the dose expansion phase. Dose Expansion: VVD-130850 + Pembrolizumab Combination Therapy Pembrolizumab Participants will receive VVD-130850 at RDE orally, once daily along with pembrolizumab IV infusion, Q3W in 21-day treatment cycles during the dose expansion phase.
- Primary Outcome Measures
Name Time Method Dose Escalation: Incidence and Severity of Dose-limiting Toxicities (DLTs) During DLT Observation Period From Day 1 to Day 21 of Cycle 1 [cycle length=21 days] Incidence and severity of DLTs will be assessed per DLT criteria set forth in the protocol based on adverse events (AEs) evaluated per National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Dose Expansion: Number of Participants with Clinically Significant Changes in Laboratory Evaluations Up to approximately 4 years Dose Expansion: Number of Participants with Clinically Significant Changes in Vital Signs Up to approximately 4 years Dose Expansion: Number of Participants with AEs and Serious Adverse Events (SAEs) Up to approximately 4 years
- Secondary Outcome Measures
Name Time Method Dose Escalation: QT/Corrected QT (QTc) Interval and Other Electrocardiogram (ECG) Parameters Up to approximately 4 years Number of participants with changes in QT/QTc interval and other ECG parameters will be assessed.
Dose Expansion: Overall Response Rate (ORR) Up to approximately 4 years ORR is defined as the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator assessment.
Dose Expansion: Disease Control Rate (DCR) Up to approximately 4 years DCR is defined as the percentage of participants achieving CR or PR, or stable disease (SD) per RECIST version 1.1 by investigator assessment.
Dose Escalation: Recommended Dose for Expansion (RDE) of VVD-130850 as a Single Agent and in Combination with Pembrolizumab Up to approximately 4 years The RDE will be based on safety, pharmacokinetics, pharmacodynamic biomarker data, and preliminary anti-tumor activity collected during the study as defined by the safety review committee.
Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve (AUC) of VVD-130850 Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days) Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of VVD-130850 Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days) Dose Escalation and Expansion: Apparent Terminal Half-life (t1/2) of VVD-130850 Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days) Dose Expansion: Progression-free Survival (PFS) Up to approximately 4 years PFS is defined as the time from the date of randomization to the time of confirmed disease progression or death, whichever occurs first per RECIST version 1.1 by investigator assessment.
Dose Expansion: Duration of Response (DoR) Up to approximately 4 years DOR is defined as the time from initial response of CR or PR to progressive disease or death, whichever comes first per RECIST version 1.1 by investigator assessment.
Trial Locations
- Locations (19)
Vall d'Hebron
🇪🇸Barcelona, Spain
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
NEXT Austin
🇺🇸Austin, Texas, United States
MDACC
🇺🇸Houston, Texas, United States
NEXT Dallas
🇺🇸Irving, Texas, United States
NEXT San Antonio
🇺🇸San Antonio, Texas, United States
University of Utah Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
NEXT Virginia
🇺🇸Fairfax, Virginia, United States
Blacktown Hospital
🇦🇺Blacktown, New South Wales, Australia
Orange Health Service
🇦🇺Orange, New South Wales, Australia
Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia
Cancer Research South Australia
🇦🇺Adelaide, Australia
ICON Cancer Research
🇦🇺South Brisbane, Australia
START Barcelona Hospital HM Nou Delfos
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
NEXT Madrid
🇪🇸Madrid, Spain
START Madrid CIOCC
🇪🇸Madrid, Spain
Start Madrid-FJD, Hospital Fundacion Jimenez Diaz
🇪🇸Madrid, Spain