Advanced Hematologic Tumors, Advanced Solid Tumors
Conditions
Keywords
VVD-130850, Phase I, First in Human, Cancer, small molecule, STAT3, NSCLC, STK11, LKB1, immunosuppression, Checkpoint inhibitor, PD-1
Brief 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.
Interventions
DRUGVVD-130850
Oral tablets
DRUGPembrolizumab
IV infusion
Sponsors
Vividion Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation: Incidence and Severity of Dose-limiting Toxicities (DLTs) During DLT Observation Period | From Day 1 to Day 21 of Cycle 1 [cycle length=21 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation: QT/Corrected QT (QTc) Interval and Other Electrocardiogram (ECG) Parameters | Up to approximately 4 years | Number of participants with changes in QT/QTc interval and other ECG parameters will be assessed. |
| Dose Escalation: Recommended Dose for Expansion (RDE) of VVD-130850 as a Single Agent and in Combination with Pembrolizumab | Up to approximately 4 years | 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. |
| Dose Expansion: Overall Response Rate (ORR) | 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) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator assessment. |
| Dose Expansion: Duration of Response (DoR) | 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. |
| Dose Expansion: Progression-free Survival (PFS) | 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. |
| Dose Expansion: Disease Control Rate (DCR) | 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. |
| 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) | — |
Countries
Australia, Spain, United States
Outcome results
None listed