A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-130037 in Participants With Advanced Solid Tumors

A Phase 1, Open-label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-tumor Activity of VVD-130037, a Kelch-like ECH Associated Protein 1 (KEAP1) Activator, in Participants With Advanced Solid Tumors

A FIH study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of VVD-130037 in participants with advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: VVD-130037

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Vividion Clinical Trial Call Center; Phone Number: (858) 345-9752; Email: clinicaltrials@vividion.com

Study Locations

• Spain
  • Barcelona, Spain
    • Recruiting
    • START Barcelona Hospital HM Nou Delfos
  • Madrid, Spain
    • Recruiting
    • NEXT Madrid
  • Madrid, Spain
    • Recruiting
    • START Madrid CIOCC
  • Madrid, Spain
    • Recruiting
    • START Madrid-FJD, Hospital Fundacion Jimenez Diaz
• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MDACC
    • Irving, Texas, United States, 75039
      • Recruiting
      • NEXT Dallas
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Histologically or cytologically confirmed metastatic or unresectable solid tumor.
• Measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by the Investigator.
• Have progressed on or after all prior standard-of-care therapies for metastatic disease.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• Adequate organ and marrow function as defined in the protocol.

Key Exclusion Criteria:

• Participant is known to have a mutation that has no expectation of benefit from VVD-130037. Current such mutations include the following:

  1. KEAP1 nonsense mutation (any position)
  2. KEAP1 frameshift mutation (any position)
• Any unresolved toxicity Grade ≥2 per CTCAE version 5.0 from previous anticancer treatment.
• Current or prior treatment with anti-epileptic medications for the treatment or prophylaxis of seizures.
• History of seizure or condition that may predispose to seizure.
• History or presence of central nervous system (CNS) metastases or spinal cord compression.
• Uncontrolled arterial hypertension despite optimal medical management.
• Risk factors for abnormal heart rhythm/QT prolongation as defined in the protocol.

• History of the following cardiac diseases:

  i) congestive heart failure (New York Heart Association [NYHA] Class >II), ii) unstable angina, iii) new onset angina within past 6 months, iv) myocardial Infarction within the past 6 months, v) clinically significant arrhythmias within past 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VVD-130037 Dose Escalation; Participants will receive ascending doses of VVD-130037, orally, once daily in 21-day treatment cycles.	Drug: VVD-130037; Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Dose-limiting Toxicities (DLTs) During DLT Observation Period	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.	From Day 1 to Day 21 of Cycle 1 [cycle length=21 days]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With AEs, Serious Adverse Events (SAEs), and Clinical Laboratory Abnormalities		From the administration of first dose through 30 days after last study drug administration or start of subsequent therapy (up to approximately 4 years)
Area Under the Plasma Concentration-time Curve (AUC) of VVD-130037		Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)
Maximum Observed Concentration (Cmax) of VVD-130037		Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)
Apparent Terminal Half-life (T1/2) of VVD-130037		Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)
QT/Corrected QT (QTc) Interval and Other Electrocardiogram (ECG) Parameters	Number of participants with changes in QT/QTc interval and other ECG parameters will be assessed.	Up to end of treatment (up to approximately 4 years)

Collaborators and Investigators

• Sponsor: Vividion Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 12, 2023
• First Submitted That Met QC Criteria: July 12, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; First-in-Human; KEAP1; NRF2; esophageal adenocarcinoma; small molecule; VVD-130037; squamous cell histology
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: VVD-130037-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No