A First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-130850 in Participants With Advanced Solid and Hematologic Tumors

A Phase 1, Open-Label, 2-Part, Multicenter, First-in-Human Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of the STAT3 Inhibitor VVD-130850 as Single Agent and in Combination With Checkpoint Inhibition in Participants With Advanced Solid and Hematologic Tumors

A FIH study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VVD-130850, as single agent and in combination with checkpoint inhibition, in participants with advanced solid and hematologic tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors; Advanced Hematologic Tumors
• Intervention / Treatment: Drug: Pembrolizumab; Drug: VVD-130850

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Vividion Clinical Trial Call Center; Phone Number: (858) 345-9752; Email: clinicaltrials@vividion.com

Study Locations

• Australia
  • Adelaide, Australia
    • Recruiting
    • Cancer Research South Australia
  • South Brisbane, Australia
    • Recruiting
    • ICON Cancer Research
• Spain
  • Barcelona, Spain
    • Recruiting
    • START Barcelona Hospital HM Nou Delfos
  • Madrid, Spain
    • Recruiting
    • START Madrid CIOCC
• United States
  • Texas
    • Austin, Texas, United States, 78758
      • Recruiting
      • NEXT Austin
    • Houston, Texas, United States, 77030
      • Recruiting
      • MDACC
    • Irving, Texas, United States, 75039
      • Recruiting
      • NEXT Dallas
    • San Antonio, Texas, United States, 78299
      • Recruiting
      • NEXT San Antonio
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Next Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Histologically or cytologically confirmed metastatic or unresectable solid tumor or advanced non-Hodgkin's lymphoma (NHL).
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
3. Adequate organ and bone marrow function as defined in the protocol.

4. For Combination Therapy Expansion:

   • Serine/threonine kinase 11/ liver kinase B1 (STK11/LKB1) mutated non-small cell lung cancer (NSCLC) as assessed by historical (local) test.
   • Must be refractory to or have progressed on or after a platinum-based doublet regimen and an immune checkpoint inhibitor (CPI). These therapies could have been given in the same line of therapy or different lines of therapy.
5. Measurable disease by RECIST version 1.1 as assessed by the Investigator.

Key Exclusion Criteria:

1. Have a diagnosis of immunodeficiency or are receiving systematic steroid therapy or any other form of immunosuppressive therapy.
2. Prior allogeneic transplantation.
3. History of cardiac diseases as defined in detail in the protocol.
4. Clinically significant infection or any eye infection.
5. Active central nervous system (CNS) malignancies (previously treated CNS malignancies are not exclusionary).

6. Combination Therapy Expansion:

   • Known hypersensitivity or contraindication to pembrolizumab or any of its components.
   • Any prior toxicity (Grade 3 or 4) related to immunotherapy leading to treatment discontinuation with the exception of the history of immunotherapy-related endocrinopathy controlled with ongoing medical management (e.g., hypothyroidism, adrenal insufficiency, diabetes).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: VVD-130850 Single Agent; Participants will receive ascending doses of VVD-130850, orally, once daily in 21-day treatment cycles during the dose escalation phase.	Drug: VVD-130850; Oral tablets
Experimental: Dose Escalation: VVD-130850 + Pembrolizumab Combination Therapy; Participants will receive ascending doses of VVD-130850, orally, once daily, along with pembrolizumab intravenous (IV) infusion, every 3 weeks (Q3W) in 21-day treatment cycles during the dose escalation phase.	Drug: Pembrolizumab; IV infusion; Drug: VVD-130850; Oral tablets
Experimental: Dose Expansion: VVD-130850 Single Agent; Participants will receive VVD-130850 at recommended dose for expansion (RDE), orally, once daily in 21-day treatment cycles during the dose expansion phase.	Drug: VVD-130850; Oral tablets
Experimental: Dose Expansion: VVD-130850 + Pembrolizumab Combination Therapy; Participants will receive VVD-130850 at RDE orally, once daily along with pembrolizumab IV infusion, Q3W in 21-day treatment cycles during the dose expansion phase.	Drug: Pembrolizumab; IV infusion; Drug: VVD-130850; Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Day 1 to Day 21 of Cycle 1 [cycle length=21 days]
Dose Expansion: Number of Participants with AEs and Serious Adverse Events (SAEs)		Up to approximately 4 years
Dose Expansion: Number of Participants with Clinically Significant Changes in Vital Signs		Up to approximately 4 years
Dose Expansion: Number of Participants with Clinically Significant Changes in Laboratory Evaluations		Up to approximately 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation: QT/Corrected QT (QTc) Interval and Other Electrocardiogram (ECG) Parameters	Number of participants with changes in QT/QTc interval and other ECG parameters will be assessed.	Up to approximately 4 years
Dose Escalation: Recommended Dose for Expansion (RDE) of VVD-130850 as a Single Agent and in Combination with Pembrolizumab	The RDE will be based on safety, pharmacokinetics, pharmacodynamic biomarker data, and preliminary anti-tumor activity collected during the study as defined by the safety review committee.	Up to approximately 4 years
Dose Expansion: Overall Response Rate (ORR)	ORR is defined as the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator assessment.	Up to approximately 4 years
Dose Expansion: Duration of Response (DoR)	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.	Up to approximately 4 years
Dose Expansion: Progression-free Survival (PFS)	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.	Up to approximately 4 years
Dose Expansion: Disease Control Rate (DCR)	DCR is defined as the percentage of participants achieving CR or PR, or stable disease (SD) per RECIST version 1.1 by investigator assessment.	Up to approximately 4 years
Dose Escalation and Expansion: Area Under the Plasma Concentration-time Curve (AUC) of VVD-130850		Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)
Dose Escalation and Expansion: Maximum Plasma Concentration (Cmax) of VVD-130850		Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)
Dose Escalation and Expansion: Apparent Terminal Half-life (t1/2) of VVD-130850		Predose and multiple timepoints post-dose from Cycle 1 Day 1 up to Cycle 5 Day 1 (cycle length=21 days)

Collaborators and Investigators

• Sponsor: Vividion Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 13, 2023
• First Submitted That Met QC Criteria: December 31, 2023
• First Posted (Actual): January 3, 2024

Study Record Updates

• Last Update Posted (Actual): June 18, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; NSCLC; Checkpoint inhibitor; immunosuppression; Phase I; PD-1; First in Human; STK11; LKB1; STAT3; small molecule; VVD-130850
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: VVD-130850-01; 2023-508386-32-00 (Other Identifier: EU CTIS Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No