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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06188208
• Other study ID #: VVD-130850-01
• Secondary ID: 2023-508386-32-0
• Status: Recruiting
• Phase: Phase 1
• Start date: January 5, 2024
• Est. completion date: December 2027

Study information

• Verified date: June 2024
• Source: Vividion Therapeutics, Inc.
• Contact: Vividion Clinical Trial Call Center
• Phone: (858) 345-9752
• Email: clinicaltrials[@]vividion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: December 2027
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• VVD-130850
Oral tablets
• Pembrolizumab
IV infusion

Locations

Country	Name	City	State
Australia	Cancer Research South Australia	Adelaide
Australia	ICON Cancer Research	South Brisbane
Spain	START Barcelona Hospital HM Nou Delfos	Barcelona
Spain	START Madrid CIOCC	Madrid
United States	NEXT Austin	Austin	Texas
United States	NEXT Virginia	Fairfax	Virginia
United States	MDACC	Houston	Texas
United States	NEXT Dallas	Irving	Texas
United States	NEXT San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Vividion Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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]
Primary	Dose Expansion: Number of Participants with AEs and Serious Adverse Events (SAEs)		Up to approximately 4 years
Primary	Dose Expansion: Number of Participants with Clinically Significant Changes in Vital Signs		Up to approximately 4 years
Primary	Dose Expansion: Number of Participants with Clinically Significant Changes in Laboratory Evaluations		Up to approximately 4 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)