The goal of this clinical trial is to evaluate TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade) in participants with advanced selected solid tumors, who have failed or are not eligible for standard of care. The main questions it aims to answer are:
1. To evaluate the safety and tolerability of TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade) 2. To determine the maximum tolerated dose or the recommended phase 2 dose of TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade) 3. To obtain a preliminary estimate of efficacy of TT-10, TT-4 and TT-10 + TT-4, (Dual Blockade) in advanced solid tumors.
Participants must be ≥18 years of age.
Participants or their legal representative must be able to provide written informed consent to participate in the study prior to the performance of any study-specific procedures.
RCC: Participants with locally advanced or metastatic RCC that have previously received at least two prior systemic regimens, including vascular endothelial growth factor (VEGF)-targeted therapy and checkpoint inhibitor therapy
CRPC: Participants with metastatic CRPC who have previously received a second-generation hormonal agent (unless contraindicated) and a taxane-based chemotherapy.
Administration of a live vaccine within 6 weeks of first dose of study intervention. Messenger ribonucleic acid (mRNA) vaccines for the prevention of Coronavirus Disease 2019 (COVID-19) infection are permitted.
Baseline QT interval corrected with Fridericia's method (QTcF) > 470 ms (average of triplicate readings)
Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
Female participants who are pregnant or breastfeeding
Sequential
TT-10
DrugTT-10 orally administered BID
TT-4
DrugTT-4 is orally administered QD
Number of subjects with Dose Limiting Toxicities (DLTs) of TT-10, TT-4 and TT-10 + TT-4 during the dose escalation phase
All toxicities will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Define the maximum tolerated dose (MTD) or phase 2 recommended dose of TT-10, TT-4 and TT-10 + TT-4 during the dose escalation phase
To confirm the maximum tolerated dose (MTD) of TT-10, TT-4 and TT-10 + TT-4, defined as the highest dose level at which \<2 out of 6 participants experience a dose-limiting toxicity
Expansion cohort primary objective - safety
Incidence and severity of treatment-related adverse events (TRAEs) in participants treated at the recommended phase 2 dose in the expansion phase
Overall Response Rate (ORR)
ORR is to be reported as the proportion of patients who have a Complete Response or Partial Response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Duration of Response (DoR)
Defined as the time from first documented objective response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 to the date of first documented radiographic progression of disease (PD) or death.
Progression Free Survival (PFS)
Time from first dose to the date of the first confirmed documented progression per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
Peak serum concentration (Cmax) of TT-10
PK Parameter
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