Recruiting
Phase 1

VVD-130037

Sponsor:

Vividion Therapeutics, Inc.

Code:

NCT05954312

Conditions

Advanced Solid Tumors

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

VVD-130037

Docetaxel

Paclitaxel

Pembrolizumab

Study Details

Brief summary:

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.

Conditions

Advanced Solid Tumors

Study ID

NCT05954312

Start date

Jul 28, 2023

Status verified date

May, 2026

Completion date

Feb 28, 2031

Anticipated

Primary completion date

Aug 31, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

290 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1 (Dose Escalation): VVD-130037 Single Agent

Participants will receive ascending doses of VVD-130037, orally, once or twice daily in 21-day treatment cycles during Part 1.

experimental: Part 1 (Dose Escalation): VVD-130037 and Docetaxel Combination Therapy

Participants will receive ascending doses of VVD-130037, orally, once or twice daily along with docetaxel intravenous (IV) infusion administered once every 3 weeks in 21-day treatment cycles during Part 1.

experimental: Part 1 (Dose Escalation): VVD-130037 and Paclitaxel Combination Therapy

Participants will receive ascending doses of VVD-130037, orally, once or twice daily along with paclitaxel IV infusion administered on Days 1, 8, and 15 of each 28-day treatment cycle during Part 1.

experimental: Part 2 (Dose Expansion): VVD-130037 Single Agent

Participants will receive VVD-130037 at the recommended dose for expansion (RDE), orally, once or twice daily in 21-day treatment cycles during Part 2.

experimental: Part 2 (Dose Expansion): VVD-130037 and Docetaxel Combination Therapy

Participants will receive VVD-130037 at the RDE, orally, once or twice daily along with docetaxel IV infusion administered once every 3 weeks in 21-day treatment cycles during Part 2.

experimental: Part 2 (Dose Expansion): VVD-130037 and Paclitaxel Combination Therapy

Participants will receive VVD-130037 at the RDE, orally, once or twice daily along with paclitaxel IV infusion administered on Days 1, 8, and 15 of each 28-day treatment cycle during Part 2.

experimental: Experimental: Part 2 (Dose Expansion): VVD-130037 and Pembrolizumab Combination Therapy

Participants will first be evaluated in a safety-run in cohort to determine the RDE(s). Participants will then receive VVD-130037 at the RDE, orally, once or twice daily along with pembrolizumab IV infusion administered once every 3 weeks in 21-day treatment cycles during Part 2.

Interventions

VVD-130037

Oral tablets

Docetaxel

IV infusion

Paclitaxel

IV infusion

Pembrolizumab

IV infusion

Primary outcome measure

  • Part 1 (Dose Escalation): Incidence and Severity of Dose-limiting Toxicities (DLTs) During DLT Observation Period [ Time Frame: 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] ]
  • Part 2 (Dose Expansion): Number of Participants With AEs, Serious Adverse Events (SAEs), and Clinical Laboratory Abnormalities [ Time Frame: Up to approximately 4 years ]

Central Contacts and Locations

Central contacts

Vividion Clinical Trial Call Center

(858) 345-9752clinicaltrials@vividion.com

Locations

Mayo Clinic Jacksonville

Recruiting

Jacksonville, Florida, United States, 32224

Florida Cancer Specialists

Recruiting

Sarasota, Florida, United States, 34232

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Mayo Clinic Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Sarah Cannon Research Institute

Recruiting

Nashville, Tennessee, United States, 37203

MDACC

Recruiting

Houston, Texas, United States, 77030

NEXT Dallas

Recruiting

Irving, Texas, United States, 75039

NEXT Virginia

Recruiting

Fairfax, Virginia, United States, 22031

More Information

Sponsor

Vividion Therapeutics, Inc.

Last update posted

May 8, 2026

Last verified

May, 2026

Keywords

  • VVD-130037
  • First-in-Human
  • KEAP1
  • NRF2
  • Cancer
  • small molecule
  • squamous cell histology
  • esophageal adenocarcinoma

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Vividion Therapeutics, Inc. on 2026-05-08.