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 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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Docetaxel; Drug: Paclitaxel; Drug: Pembrolizumab; Drug: VVD-130037

• Study Type: Interventional
• Enrollment (Estimated): 290
• 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

• South Korea
  • Goyang, South Korea
    • Recruiting
    • National Cancer Center
  • Goyang, South Korea
    • Recruiting
    • The Catholic university of Korea, St. Vincent's Hospital
    • Contact: Vividion Call Center; Phone Number: +1 8583459752
  • Incheon, South Korea
    • Recruiting
    • Gachon University Gil Medical Center
  • Seongnam, South Korea
    • Recruiting
    • Seoul National University; Bundang Hospital
  • Seoul, South Korea
    • Recruiting
    • Samsung Medical Center
  • Seoul, South Korea
    • Recruiting
    • Seoul National University Hospital
  • Seoul, South Korea
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea
    • Recruiting
    • Severance Hospital; Yonsei University Health System
  • Suwon, South Korea
    • Recruiting
    • The Catholic university of Korea, St. Vincent's Hospital
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Vall d'Hebron
  • Barcelona, Spain
    • Recruiting
    • START Barcelona Hospital HM Nou Delfos
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain
    • Recruiting
    • NEXT Madrid
  • Madrid, Spain
    • Recruiting
    • START Madrid CIOCC
  • Madrid, Spain
    • Recruiting
    • Start Madrid-FJD, Hospital Fundacion Jimenez Diaz
  • Pamplona, Spain
    • Recruiting
    • Clinica Universitaria De Navarra
  • Valencia, Spain
    • Recruiting
    • Hospital Clinico Universitario de Valencia
• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Jacksonville
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Rochester
  • 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 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 Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: VVD-130037; Oral tablets
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.	Drug: Docetaxel; IV infusion; Drug: VVD-130037; Oral tablets
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.	Drug: Paclitaxel; IV infusion; Drug: VVD-130037; Oral tablets
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.	Drug: VVD-130037; Oral tablets
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.	Drug: Docetaxel; IV infusion; Drug: VVD-130037; Oral tablets
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.	Drug: Paclitaxel; IV infusion; Drug: VVD-130037; Oral tablets
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.	Drug: Pembrolizumab; IV infusion; Drug: VVD-130037; Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2 (Dose Expansion): Number of Participants With AEs, Serious Adverse Events (SAEs), and Clinical Laboratory Abnormalities		Up to approximately 4 years
Part 1 (Dose Escalation): 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.	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]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 (Dose Escalation): Number of Participants With AEs, SAEs, and Clinical Laboratory Abnormalities		Up to approximately 4 years
Part 2 (Dose Expansion): Overall Response Rate (ORR)	ORR is defined as the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator assessment.	Up to approximately 4 years
Part 2 (Dose Expansion): Duration of Response (DOR)	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.	Up to approximately 4 years
Part 2 (Dose Expansion): Progression-free Survival (PFS)	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.	Up to approximately 4 years
Part 2 (Dose Expansion): Disease Control Rate (DCR)	DCR is defined as the percentage of participants achieving CR or PR, or stable disease (SD) per RECIST version 1.1 by investigator assessment.	Up to approximately 4 years
Parts 1 and 2 (Dose Escalation and Expansion): 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.	Parts 1 and 2: Up to approximately 4 years
Part 2 (Dose Expansion): Recommended Phase 2 Dose (RP2D) of VVD-130037 as a Single Agent and in Combination with Docetaxel, Paclitaxel, or Pembrolizumab	The RP2D will be based on safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of VVD-130037 as single agent, and in combination with docetaxel, paclitaxel, or pembrolizumab during Part 2.	Up to approximately 4 years
Parts 1 and 2 (Dose Escalation and Expansion): Area Under the Plasma Concentration-time Curve (AUC) of VVD-130037		Parts 1 and 2: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days for Single Agent and Docetaxel/Pembrolizumab Combination Therapy and cycle length=28 days for Paclitaxel Combination Therapy)
Parts 1 and 2 (Dose Escalation and Expansion): Maximum Observed Concentration (Cmax) of VVD-130037		Parts 1 and 2: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days for Single Agent and Docetaxel/Pembrolizumab Combination Therapy and cycle length=28 days for Paclitaxel Combination Therapy)
Parts 1 and 2 (Dose Escalation and Expansion): Apparent Terminal Half-life (T1/2) of VVD-130037		Parts 1 and 2: Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days for Single Agent and Docetaxel/Pembrolizumab Combination Therapy and cycle length=28 days for Paclitaxel Combination Therapy)

Collaborators and Investigators

• Sponsor: Vividion Therapeutics, Inc.

Publications and helpful links

General Publications

• Roy N, Wyseure T, Lo IC, Lu J, Eissler CL, Bernard SM, Bok I, Snead AN, Parker A, Lo UG, Green JC, Inloes J, Jacinto SR, Kuenzi B, Pariollaud M, Negri K, Le K, Horning BD, Ibrahim N, Grabow S, Panda H, Bhatt DP, Wilkerson EM, Saeidi S, Zolkind P, Rush Z, Williams HN, Walton E, Pastuszka MK, Sigler JJ, Tran E, Hee K, McLaughlin J, Ambrus-Aikelin G, Pollock J, Abraham RT, Kinsella TM, Simon GM, Major MB, Weinstein DS, Patricelli MP. A covalent allosteric molecular glue suppresses NRF2-dependent cancer growth. Cancer Discov. 2025 Dec 19. doi: 10.1158/2159-8290.CD-25-1187. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2023
• Primary Completion (Estimated): August 31, 2030
• Study Completion (Estimated): February 28, 2031

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): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

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; Adenocarcinoma Of Esophagus; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; Paclitaxel; pembrolizumab
• Other Study ID Numbers: VVD-130037-001; 2023-506199-28-00 (Ctis)

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
• product manufactured in and exported from the U.S.: No