Clinical trial NCT05954312: A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-130037 in Participants With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: VVD-130037
First-in-Human
KEAP1
NRF2
Cancer
small molecule
squamous cell histology
esophageal adenocarcinoma
Lead sponsor: Vividion Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-07-20
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A FIH dose escalation and dose expansion study to evaluate VVD-130037 in participants with advanced solid tumors as a single agent, in combination with docetaxel, and in combination with paclitaxel.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1 (Dose Escalation): Incidence and Severity of Dose-limiting Toxicities (DLTs) During DLT Observation Period
timeFrame: Part 1: Single Agent and Docetaxel Combination Therapy Cohorts: From Day 1 to Day 21 of Cycle 1 [cycle length=21 days] and Part 1: Paclitaxel Combination Therapy Cohort: From Day 1 to Day 28 of Cycle 1 [cycle length=28 days]
measure: Part 2 (Dose Expansion): Number of Participants With AEs, Serious Adverse Events (SAEs), and Clinical Laboratory Abnormalities
timeFrame: Up to approximately 4 years
Secondary outcomes:
measure: Part 1 (Dose Escalation): Number of Participants With AEs, SAEs, and Clinical Laboratory Abnormalities
timeFrame: Up to approximately 4 years
measure: Part 2 (Dose Expansion): Recommended Phase 2 Dose (RP2D) of VVD-130037 as a Single Agent and in Combination with Docetaxel and Paclitaxel
timeFrame: Up to approximately 4 years
measure: Part 2 (Dose Expansion): Overall Response Rate (ORR)
timeFrame: Up to approximately 4 years
measure: Part 2 (Dose Expansion): Duration of Response (DOR)
timeFrame: Up to approximately 4 years
measure: Part 2 (Dose Expansion): Progression-free Survival (PFS)
timeFrame: Up to approximately 4 years
measure: Part 2 (Dose Expansion): Disease Control Rate (DCR)
timeFrame: Up to approximately 4 years
measure: 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 Combination Therapy Cohorts and cycle length=28 days for Paclitaxel Combination Therapy Cohorts)
measure: 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 Combination Therapy Cohorts and cycle length=28 days for Paclitaxel Combination Therapy Cohorts)
measure: 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 Combination Therapy Cohorts and cycle length=28 days for Paclitaxel Combination Therapy Cohorts)
measure: 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
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MDACC
state: Texas
city: Irving
country: United States
facility: NEXT Dallas
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: START Barcelona Hospital HM Nou Delfos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: NEXT Madrid
city: Madrid
country: Spain
facility: START Madrid CIOCC
city: Madrid
country: Spain
facility: Start Madrid-FJD, Hospital Fundacion Jimenez Diaz
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
References: