Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 1

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

NCT ID: NCT05954312Sponsor: Vividion Therapeutics, Inc.Last updated: 2026-05-08

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.

Arms & interventions

  • DrugVVD-130037

    Oral tablets

  • DrugDocetaxel

    IV infusion

  • DrugPaclitaxel

    IV infusion

  • DrugPembrolizumab

    IV infusion

Outcome measures

Primary

  • 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.

    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

Secondary

  • Part 1 (Dose Escalation): Number of Participants With AEs, SAEs, and Clinical Laboratory Abnormalities

    Time frame: 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

    Time frame: Up to approximately 4 years

  • Part 2 (Dose Expansion): Overall Response Rate (ORR)

    Time frame: Up to approximately 4 years

  • Part 2 (Dose Expansion): Duration of Response (DOR)

    Time frame: Up to approximately 4 years

  • Part 2 (Dose Expansion): Progression-free Survival (PFS)

    Time frame: Up to approximately 4 years

  • Part 2 (Dose Expansion): Disease Control Rate (DCR)

    Time frame: Up to approximately 4 years

  • Parts 1 and 2 (Dose Escalation and Expansion): Area Under the Plasma Concentration-time Curve (AUC) of VVD-130037

    Time frame: 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

    Time frame: 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

    Time frame: 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): QT/Corrected QT (QTc) Interval and Other Electrocardiogram (ECG) Parameters

    Time frame: Parts 1 and 2: Up to approximately 4 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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)

Study locations (8)

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224

Recruiting

Florida Cancer Specialists

Sarasota, Florida, 34232

Recruiting

Moffitt Cancer Center

Tampa, Florida, 33612

Recruiting

Mayo Clinic Rochester

Rochester, Minnesota, 55905

Recruiting

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

Recruiting

MDACC

Houston, Texas, 77030

Recruiting

NEXT Dallas

Irving, Texas, 75039

Recruiting

NEXT Virginia

Fairfax, Virginia, 22031

Recruiting

References

  • 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. 2026 May 1;16(5):953-975. doi: 10.1158/2159-8290.CD-25-1187.(PubMed)