This is a phase 1b, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics of Sapu003 in combination with Exemestane in in patients with advanced mTOR-sensitive solid tumors (HR+/HER2-negative breast cancer, renal cell carcinoma \[RCC\], neuroendocrine tumors \[NETs\], tuberous sclerosis complex \[TSC\]-associated tumors, and hepatocellular carcinoma \[HCC\]).
Sex and Age: Patients must be ≥ 18 years of age at the time of informed consent.
Cohort A (HR+/HER2- breast cancer): Eligible patients must be postmenopausal women, defined as women ≥ 18 years of age with amenorrhea for ≥ 12 consecutive months without another pathophysiological cause.
Cohort B (RCC, NETs, TSC-associated tumors, HCC): Eligible patients include both male and female adults with advanced disease.
Has histologically or cytologically documented advanced (metastatic or unresectable) hormone receptor-positive, HER2 negative breast cancer (advanced HR+ BC)
Patients with a history of other malignancies, except for adequately treated non-melanoma skin cancer, curatively treated in-situ carcinoma of the cervix, curatively treated in-situ carcinoma of the breast, or other solid tumors curatively treated with no evidence of disease for > 5 years.
Patients who have not completely recovered from any toxicities from previous chemotherapy, hormone therapy, immunotherapy, target therapy, or radiotherapies ≥ Grade 1 per NCI CTCAE version 5.0, with the exception of alopecia.
Prior chemotherapy within 30 days prior to screening (42 days for mitomycin C or nitrosoureas).
Prior immunotherapy, prior anti-tumor hormonal therapy (for breast cancer patients), and prior radiotherapy within 30 days prior to screening.
Sequential
Sapu003
DrugSapu003 weekly IV at 5, 7.5 or 10 mg/m²
Exemestane 25 MG
DrugExemestane 25 mg QD (Breast Cancer Only)
Maximum Tolerated Dose (MTD) and Dose Limiting Toxicities (DLTs) of Sapu003 in Patients with Advanced mTOR-Sensitive Solid Tumors
The primary outcome of the study is to determine the Maximum Tolerated Dose (MTD) of Sapu003, defined as the dose level where the estimated true probability of Dose-Limiting Toxicity (DLT) is closest to the target toxicity probability (TTP) of 0.27. This will be evaluated through a dose-escalation design, where patients receive Sapu003 intravenously every week, with doses ranging from 5 to 10 mg/m². The analysis will include the cumulative number of DLTs observed at each dose level, guiding decisions for dose escalation or de-escalation, ultimately reporting the recommended MTD based on isotonic regression estimates
Pharmacokinetic Endpoint - Cmax
Characterization of the Pharmacokinetic Endpoint - Peak Plasma Concentration (Cmax)
Pharmacokinetic Endpoint - AUClast
Characterization of the Pharmacokinetic Endpoint - Area Under the Curve from time zero to the last quantifiable concentration (AUClast)
Pharmacokinetic Endpoint - AUCinf
Characterization of the Pharmacokinetic Endpoint - Area Under the Curve to Infinity (AUCinf)
Pharmacokinetic Endpoint - tmax
Characterization of the Pharmacokinetic Endpoint - Time to reach maximum concentration (tmax)
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