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

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

Official Title
-----------------
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

Conditions
-----------------
Advanced Solid Tumors

Intervention / Treatment
-----------------
* Drug: VVD-130037


Participation Criteria
=================
Eligibility Criteria
-----------------
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: KEAP1 nonsense mutation (any position) 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

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) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
VVD-130037, First-in-Human, KEAP1, NRF2, Cancer, small molecule, squamous cell histology, esophageal adenocarcinoma