Sapu003 in Advanced mTOR-sensitive Solid Tumors

NCT07369505 | Recruiting Phase 1

• 1 other identifier: SP-03-B101
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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 \[HCC\]).

Conditions

Breast Cancer Metastatic; Renal Cell Carcinoma (RCC); Neuroendocrine Tumors; Tuberous Sclerosis Complex (TSC); Hepatocellular Carcinoma (HCC)

Keywords

Sapu003; Everolimus for Injection; mTOR-Sensitive Solid Tumors; Renal Cell Carcinoma (RCC); Neuroendocrine Tumors (NETs); Tuberous Sclerosis Complex (TSC); Hepatocellular Carcinoma (HCC); everolimus; HR+/HER2-negative breast cancer

Outcome Measures

Primary Outcomes (1)

• 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

  The primary outcome timeframe is assessed during the first 28-day cycle of treatment, specifically looking at dose-limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) of Sapu003

Secondary Outcomes (12)

• Pharmacokinetic Endpoint - Cmax

  Week 1 of Cycle 1 and Cycle 2 (28 days per Treatment Cycle)

• Pharmacokinetic Endpoint - AUClast

  Week 1 of Cycle 1 and Cycle 2 (28 days per Treatment Cycle)

• Pharmacokinetic Endpoint - AUCinf

  Week 1 of Cycle 1 and Cycle 2 (28 days per Treatment Cycle)

• Pharmacokinetic Endpoint - tmax

  Week 1 of Cycle 1 and Cycle 2 (28 days per Treatment Cycle)

• Characterization of the Pharmacokinetic Endpoint - t1/2

  Week 1 of Cycle 1 and Cycle 2 (28 days per Treatment Cycle)

Study Arms (2)

Cohort A - HR+/HER2- Breast Cancer

EXPERIMENTAL

Cohort A (Combination Therapy - HR+/HER2- Breast Cancer): Post-menopausal women with advanced or metastatic hormone-receptor-positive, HER2-negative breast cancer receive Sapu003 (everolimus for injection) as a 30-min IV infusion once weekly at 5, 7.5 or 10 mg/m², together with oral exemestane 25 mg once daily, repeated in 28-day cycles.

Drug: Sapu003; Drug: Exemestane 25 MG

Cohort B - RCC / NET / TSC / HCC

EXPERIMENTAL

Cohort B (Monotherapy - RCC / NET / TSC / HCC): Adult patients with advanced renal cell carcinoma, neuro-endocrine tumours, tuberous-sclerosis-complex-associated tumours, or hepatocellular carcinoma receive Sapu003 (everolimus for injection) alone as a 30-min infusion once weekly at 5, 7.5 or 10 mg/m², repeated in 28-day cycles.

Drug: Sapu003

Interventions

Sapu003 DRUG

Sapu003 weekly IV at 5, 7.5 or 10 mg/m²

Also known as: Sapu003/Everolimus for Injection

Cohort A - HR+/HER2- Breast Cancer; Cohort B - RCC / NET / TSC / HCC

Exemestane 25 MG DRUG

Exemestane 25 mg QD (Breast Cancer Only)

Also known as: Exemestane

Cohort A - HR+/HER2- Breast Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Cohort A HR+/HER2- Breast Cancer:
• Eligible patients must meet all of the following:
• Has histologically or cytologically documented advanced (metastatic or unresectable) hormone receptor-positive, HER2 negative breast cancer (advanced HR+ BC)
• Has stage IV or locally advanced breast cancer per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Seventh Edition;
• Has failed any combination endocrine therapy or relapse within 6 months of adjuvant chemotherapy for metastatic or locally advanced disease. Prior therapy should have included a non-steroidal aromatase inhibitor unless clinically contraindicated;
• Has agreed to participate in the study and signed the informed consent form prior to participation in any study activities.
• Cohort B Other Advanced mTOR-Sensitive Solid Tumors:
• Eligible patients must meet all of the following:
• Has histologically or cytologically confirmed advanced (metastatic or unresectable) disease in one of the following tumor types:
• Renal Cell Carcinoma (RCC)
• Neuroendocrine Tumors (NETs)
• Tuberous Sclerosis Complex (TSC)-associated tumors

You may not qualify if:

• 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.
• Patients who have received any of the following treatments within the specified timeframes prior to screening:
• 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.
• Radiotherapy is not allowed during study. Administration of other chemotherapy, immunotherapy, or anti-tumor hormonal therapy during the study is not allowed.
• Patients had major surgery within 30 days prior to randomization, or patients have not recovered from prior major surgery.
• Sensory / Peripheral neuropathy of \> Grade 1 per NCI CTCAE version 5.0 at Screening.
• Patients with active brain metastases. Patients with treated brain metastases are eligible provided they have no evidence of active brain disease and are off of definitive therapy (including steroids) at least 3 months prior to randomization.
• Known history or presence of any clinically significant disease or condition other than cancer unless determined as not clinically significant by the Principal Investigator/Sub-Investigator. This includes, but is not limited to, the following: hepatic, renal/genitourinary, gastrointestinal (e.g., intra-abdominal inflammation), cardiovascular (e.g., congestive heart failure, ventricular arrhythmia, myocardial infarction, unstable angina pectoris), cerebrovascular, pulmonary (e.g., interstitial lung disease), endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological, or hematological (e.g., bleeding diathesis or coagulopathy).
• History of difficulty with donating blood or difficulty in accessibility of central line.
• Known history or presence of:
• Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C (serology to confirm absence is required within 7 days prior to randomization and assessed based on local labs);
• Alcohol abuse or dependence within one year prior to randomization;
• Drug abuse or dependence (marijuana, amphetamines, barbiturates, cocaine, opiates and benzodiazepines);

Sponsors & Collaborators

• SAPU NANO (US) LLC: lead

Study Sites (1)

SOCRU

Adelaide, Australia

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neuroendocrine Tumors; Tuberous Sclerosis; Carcinoma, Hepatocellular

Interventions

Everolimus; Injections; exemestane

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Hamartoma; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Cynthia Lee

CONTACT

(650) 635-7024; cynthia.lee@sapunano.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase 1b, open-label, sequential-assignment, dose-escalation study that uses a model-assisted Bayesian Optimal Interval (BOIN) design to guide intra-subject and inter-cohort dose decisions. Participants are enrolled in cohorts of three (with staggered "sentinel" dosing within each cohort) and receive once-weekly IV Sapu003 for four weeks per 28-day cycle. Two parallel disease-defined cohorts are studied: * Cohort A (HR+/HER2- breast cancer) - Sapu003 + daily oral exemestane * Cohort B (RCC, NETs, TSC-associated tumors, or HCC) - Sapu003 monotherapy Dose escalation proceeds from 5 mg/m² to 7.5 mg/m² to 10 mg/m² (with an optional -1 level of 3.5 mg/m²) according to BOIN escalation (λe ≈ 0.213) and de-escalation (λd ≈ 0.322) boundaries that target a DLT rate of 27 % during Cycle 1. Each dose level may expand to nine evaluable subjects; maximum sample size for the MTD determination is 27.

Study Record Dates

• First Submitted: January 2, 2026
• First Posted: January 27, 2026
• Study Start: December 15, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)