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

Vividion Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: VVD-130037; Drug: Paclitaxel; Drug: Docetaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT05954312

2023-506199-28-00 (EU Trial (CTIS) Number)

VVD-130037-001

Details and patient eligibility

About

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.

Enrollment: 280 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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280 participants in 6 patient groups

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

Experimental group

Description:

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

Treatment:

Drug: VVD-130037

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

Experimental group

Description:

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.

Treatment:

Drug: Docetaxel

Drug: VVD-130037

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: VVD-130037

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

Experimental group

Description:

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.

Treatment:

Drug: VVD-130037

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

Experimental group

Description:

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.

Treatment:

Drug: Docetaxel

Drug: VVD-130037

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

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: VVD-130037