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

NCT05954312
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
290
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Lead sponsor
Vividion Therapeutics, Inc.
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Start date
2023-07-28
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Number of sites
26
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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.
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Short title
A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-130037 in Participants With Advanced Solid Tumors
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Official title
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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2031-02-28
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First posted
2023-07-20
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Registry last updated
2026-05-08
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Primary completion date
2030-08-31
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Start date
2023-07-28
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Participants
290
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Participant count basis
Estimated
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Planned participants
290
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Protocol amendments
3
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Number of sites
26
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Vividion Therapeutics, Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05954312
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ClinicalTrials.gov ID
NCT05954312
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Registry record
Open registry record
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Allocation
Randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Part 1 (Dose Escalation): Incidence and Severity of Dose-limiting Toxicities (DLTs) During DLT Observation Period

    Timeframe: 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.

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

    Timeframe: Up to approximately 4 years

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

    Timeframe: Up to approximately 4 years

  2. Part 2 (Dose Expansion): Recommended Phase 2 Dose (RP2D) of VVD-130037 as a Single Agent and in Combination with Docetaxel, Paclitaxel, or Pembrolizumab

    Timeframe: Up to approximately 4 years

    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.

  3. Part 2 (Dose Expansion): Overall Response Rate (ORR)

    Timeframe: Up to approximately 4 years

    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.

  4. Part 2 (Dose Expansion): Duration of Response (DOR)

    Timeframe: Up to approximately 4 years

    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.

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

    Timeframe: Up to approximately 4 years

    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.

  6. Part 2 (Dose Expansion): Disease Control Rate (DCR)

    Timeframe: Up to approximately 4 years

    DCR is defined as the percentage of participants achieving CR or PR, or stable disease (SD) per RECIST version 1.1 by investigator assessment.

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

    Timeframe: 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)

  8. Parts 1 and 2 (Dose Escalation and Expansion): Maximum Observed Concentration (Cmax) of VVD-130037

    Timeframe: 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)

  9. Parts 1 and 2 (Dose Escalation and Expansion): Apparent Terminal Half-life (T1/2) of VVD-130037

    Timeframe: 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)

  10. Parts 1 and 2 (Dose Escalation and Expansion): QT/Corrected QT (QTc) Interval and Other Electrocardiogram (ECG) Parameters

    Timeframe: Parts 1 and 2: Up to approximately 4 years

    Number of participants with changes in QT/QTc interval and other ECG parameters will be assessed.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
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)

Sources for eligibility
clinicaltrials.gov

  • Mayo Clinic JacksonvilleJacksonville, United StatesRecruiting
  • Florida Cancer SpecialistsSarasota, United StatesRecruiting
  • Moffitt Cancer CenterTampa, United StatesRecruiting
  • Mayo Clinic RochesterRochester, United StatesRecruiting
  • Sarah Cannon Research InstituteNashville, United StatesRecruiting
  • MDACCHouston, United StatesRecruiting
  • NEXT DallasIrving, United StatesRecruiting
  • NEXT VirginiaFairfax, United StatesRecruiting
  • National Cancer CenterGoyang, South KoreaRecruiting
  • The Catholic University of Korea, St. Vincent's HospitalGoyang, South KoreaRecruiting
  • Gachon University Gil Medical CenterIncheon, South KoreaRecruiting
  • Seoul National University; Bundang HospitalSeongnam, South KoreaRecruiting
  • Asan Medical CenterSeoul, South KoreaRecruiting
  • Samsung Medical CenterSeoul, South KoreaRecruiting
  • Seoul National University HospitalSeoul, South KoreaRecruiting
  • Severance Hospital; Yonsei University Health SystemSeoul, South KoreaRecruiting
  • The Catholic University of Korea, St. Vincent's HospitalSuwon, South KoreaRecruiting
  • Hospital Vall d'HebronBarcelona, SpainRecruiting
  • START Barcelona Hospital HM Nou DelfosBarcelona, SpainRecruiting
  • Hospital Universitario 12 de OctubreMadrid, SpainRecruiting
  • Hospital Universitario Ramon y CajalMadrid, SpainRecruiting
  • NEXT MadridMadrid, SpainRecruiting
  • START Madrid CIOCCMadrid, SpainRecruiting
  • Start Madrid-FJD, Hospital Fundacion Jimenez DiazMadrid, SpainRecruiting
  • Clinica Universitaria de NavarraPamplona, SpainRecruiting

And 1 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-506199-28-00
Sources for references
clinicaltrials.gov

Related records

Drugs (3)

Lead sponsors (1)

Conditions (1)

Targets (16)