This study is to evaluate the safety and tolerability to determine (i) the recommended Phase 2 dose (RP2D) of VMD-102 (Phase 1), and (ii) preliminary anti-tumor efficacy (Phase 2), in participants with advanced HCC, metastatic uveal melanoma (MUM), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). The pharmacokinetics (PK), preliminary anti-tumor activity, and potential biomarkers of VMD-102 will also be assessed.
VMD-102 will be the first selective PKC epsilon (PKCε or PKCe) kinase inhibitor to enter human clinical testing. Preclinical VMD-102 anti-tumor activities in mouse liver/HCC tumor models and preclinical toxicology and pharmacology studies support this study.
Histological or cytological or radiological diagnosis of advanced (unresectable and/or metastatic) HCC, MUM, RCC, NSCLC and CRC that is not responsive to standard of care (SOC), had progressed following SOC, is intolerant to SOC, or for whom the SOC is not considered appropriate by the investigator.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0, or 1.
Has at least one measurable target lesion according to RECIST v1.1 [Response Evaluation Criteria In Solid Tumors], or mRECIST [modified RECIST] for unresectable HCC participants, and either (a). has not been previously treated with local therapy (e.g., radiation therapy, hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy), or (b). if the target lesion was within the field of local therapy, the lesion has shown an increase in size of 25% or greater following local therapy.
Hemoglobin ≥ 9 g/dL (SI Units: 90 g/L) (post-transfusion if transfusion-dependent)
Received anticancer therapy with radiation, immunotherapy, a biologic, surgery and/or tumor embolization within the past 2 weeks or 5 half-lives (whichever is longer).
Currently pregnant, nursing, or planning to become pregnant during the course of study.
The Fridericia Corrected QT (QTcF) interval ≥ 480 msec.
Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system (Section 14.8); or presence of clinically significant and uncontrolled cardiac disease, as assessed by the investigator. Such as but not limited to: symptomatic congestive heart failure, unstable angina, cardiac arrhythmia.
Sequential
VMD-102
DrugA small organic molecule oral drug in the tablet form
Number and severity of treatment-emergent adverse events (TEAE) (Phase 1)
TEAE
To determine the recommended Phase 2 dose (RP2D) for VMD-102 (Phase 1)
RP2D
Progression-Free Survival (PFS) (Phase 2)
Defined as the time from enrollment to tumor progression or death from any cause.
Area under the plasma concentration versus time curve (AUC) of VMD-102
AUC
Peak plasma concentration (Cmax) of VMD-102
Cmax
Incidence of Dose Limiting Toxicities
\# of DLTs
Objective Response Rate (ORR)
The proportion of patients with objective tumor response, as evaluated by the investigator, including cases of complete response (CR) and partial response (PR).
Click on the lead sponsor to view all of their trials.
