A FIH dose escalation and dose expansion study to evaluate VVD-130037 in participants with advanced solid tumors as a single agent, and in combination with docetaxel, paclitaxel, or pembrolizumab.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Key Inclusion Criteria for Parts 1 and 2:
* 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.
Additional Key Inclusion Criteria for Part 2:
* Participants with squamous non-small cell lung cancer (sqNSCLC) with or without nuclear factor erythroid 2-related factor 2 (NRF2 \[NFE2L2\]) and/or cullin 3 (CUL3) mutations.
* Participants with advanced sqNSCLC must be refractory to or have progressed on or after a platinum-based doublet regimen and an immune checkpoint inhibitor.
* Participants with advanced head and neck squamous cell carcinoma (HNSCC) must have received prior treatment with platinum-based chemotherapy, an immune checkpoint inhibitor (for tumors with known programmed death-ligand 1 \[PD-L1\] expression, microsatellite instability-high, or mismatch repair deficiency, and an anti-epidermal growth factor receptor agent) (Combination Expansion Cohort).
* Participants with advanced esophageal squamous cell carcinoma (ESCC) must have received prior treatment with platinum-based chemotherapy, an immune checkpoint inhibitor (for tumors with known PD-L1 expression) (Combination Expansion Cohort).
* Participants with a known driver mutation, including activating epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, should have progressed after appropriate targeted treatment.
* Participants with known human epidermal growth factor receptor 2 overexpression should have progressed after appropriate targeted treatment.
Key Exclusion Criteria for Parts 1 and 2:
* 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.
* Any prior toxicity (Grade 3 or 4) related to immunotherapy leading to treatment discontinuation (Combination Expansion Cohort)
* Medical history of (noninfectious) pneumonitis/interstitial lung disease (ILD), drug induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active pneumonitis/ILD (Combination Expansion Cohort)
Primary outcome measure(s)
Part 1 (Dose Escalation): Incidence and Severity of Dose-limiting Toxicities (DLTs) During DLT Observation Period — Part 1: Single Agent and Docetaxel/Pembrolizumab Combination Therapy: From Day 1 to Day 21 of Cycle 1 [cycle length=21 days] and Part 1: Paclitaxel Combination Therapy: From Day 1 to Day 28 of Cycle 1 [cycle length=28 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.
Part 2 (Dose Expansion): Number of Participants With AEs, Serious Adverse Events (SAEs), and Clinical Laboratory Abnormalities — Up to approximately 4 years
Trial sites (26)
Facility
City
Region
Status
Mayo Clinic Jacksonville
Jacksonville
Florida
Recruiting
Florida Cancer Specialists
Sarasota
Florida
Recruiting
Moffitt Cancer Center
Tampa
Florida
Recruiting
Mayo Clinic Rochester
Rochester
Minnesota
Recruiting
Sarah Cannon Research Institute
Nashville
Tennessee
Recruiting
MDACC
Houston
Texas
Recruiting
NEXT Dallas
Irving
Texas
Recruiting
NEXT Virginia
Fairfax
Virginia
Recruiting
National Cancer Center
Goyang
South Korea
Recruiting
The Catholic University of Korea, St. Vincent's Hospital
Goyang
South Korea
Recruiting
Gachon University Gil Medical Center
Incheon
South Korea
Recruiting
Seoul National University; Bundang Hospital
Seongnam
South Korea
Recruiting
Asan Medical Center
Seoul
South Korea
Recruiting
Samsung Medical Center
Seoul
South Korea
Recruiting
Seoul National University Hospital
Seoul
South Korea
Recruiting
Severance Hospital; Yonsei University Health System
Seoul
South Korea
Recruiting
The Catholic University of Korea, St. Vincent's Hospital
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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