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

NCT05954312 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: VVD-130037-0012023-506199-28-00
• Study Type: interventional
• Target: 290
• Locations: 3 countries
• Sites: 25

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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]

• Part 2 (Dose Expansion): Number of Participants With AEs, Serious Adverse Events (SAEs), and Clinical Laboratory Abnormalities

  Up to approximately 4 years

Secondary Outcomes (10)

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

  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

  Up to approximately 4 years

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

  Up to approximately 4 years

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

  Up to approximately 4 years

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

  Up to approximately 4 years

Study Arms (7)

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

EXPERIMENTAL

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

Drug: VVD-130037

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

EXPERIMENTAL

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: VVD-130037; Drug: Docetaxel

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

EXPERIMENTAL

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: VVD-130037; Drug: Paclitaxel

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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: VVD-130037; Drug: Docetaxel

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

EXPERIMENTAL

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: VVD-130037; Drug: Paclitaxel

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

EXPERIMENTAL

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: VVD-130037; Drug: Pembrolizumab

Interventions

VVD-130037 DRUG

Oral tablets

Experimental: Part 2 (Dose Expansion): VVD-130037 and Pembrolizumab Combination Therapy; Part 1 (Dose Escalation): VVD-130037 Single Agent; Part 1 (Dose Escalation): VVD-130037 and Docetaxel Combination Therapy; Part 1 (Dose Escalation): VVD-130037 and Paclitaxel Combination Therapy; Part 2 (Dose Expansion): VVD-130037 Single Agent; Part 2 (Dose Expansion): VVD-130037 and Docetaxel Combination Therapy; Part 2 (Dose Expansion): VVD-130037 and Paclitaxel Combination Therapy

Docetaxel DRUG

IV infusion

Part 1 (Dose Escalation): VVD-130037 and Docetaxel Combination Therapy; Part 2 (Dose Expansion): VVD-130037 and Docetaxel Combination Therapy

Paclitaxel DRUG

IV infusion

Part 1 (Dose Escalation): VVD-130037 and Paclitaxel Combination Therapy; Part 2 (Dose Expansion): VVD-130037 and Paclitaxel Combination Therapy

Pembrolizumab DRUG

IV infusion

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Vividion Therapeutics, Inc.: lead

Study Sites (25)

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

RECRUITING

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

MDACC

Houston, Texas, 77030, United States

RECRUITING

NEXT Dallas

Irving, Texas, 75039, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

National Cancer Center

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

Suwon, South Korea

RECRUITING

Hospital Vall d'Hebron

Barcelona, Spain

RECRUITING

START Barcelona Hospital HM Nou Delfos

Barcelona, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, Spain

RECRUITING

NEXT Madrid

Madrid, Spain

RECRUITING

START Madrid CIOCC

Madrid, Spain

RECRUITING

Start Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, Spain

RECRUITING

Clinica Universitaria de Navarra

Pamplona, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, Spain

RECRUITING

Related Publications (1)

• 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.

  PMID: 41417010 DERIVED

MeSH Terms

Conditions

Neoplasms; Adenocarcinoma Of Esophagus

Interventions

Docetaxel; Paclitaxel; pembrolizumab

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Central Study Contacts

Vividion Clinical Trial Call Center

CONTACT

(858) 345-9752; clinicaltrials@vividion.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2023
• First Posted: July 20, 2023
• Study Start: July 28, 2023
• Primary Completion (Estimated): August 31, 2030
• Study Completion (Estimated): February 28, 2031
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (8); KR (8); ES (9)