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 Diacid, and combination therapy (TT-10 + TT-4 Diacid). 2. To determine the maximum tolerated dose (MTD) or phase 2 recommended dose of TT-10, TT-4 Diacid, and combination therapy (TT-10 + TT-4 Diacid). 3. To evaluate safety of combination therapy (TT-10 + TT-4 Diacid).
Male or female participants must be ≥18 years of age on the day of signing the ICF.
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 who have previously received at least two prior standard of care systemic regimens for advanced disease. Prior exposure to a checkpoint inhibitor and/or vascular endothelial growth factor (VEGF) targeted therapy is permitted but not required. Prior HIF-2α inhibitor therapy is permitted and may count toward the number of prior systemic regimens.
CRPC: Participants with metastatic CRPC who have previously received a second-generation hormonal agent (unless contraindicated) and a taxane-based chemotherapy.
Major surgery within 4 weeks prior to Screening
Participants with active CNS metastases are excluded.
Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
Prior anti-cancer therapy within 4 weeks prior to the start of study intervention. A 2 week washout is acceptable for short-acting drugs (e.g., tyrosine kinase inhibitors). Any treatment-related toxicities must be resolved to Grade 0 - 1.
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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