Sapu003 with or without exemestane for advanced mTOR-sensitive solid tumors

A Phase 1b, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics of Sapu003 in Advanced mTOR-sensitive Solid Tumors (With or Without Exemestane)

This phase 1b test will try weekly IV Sapu003, given with exemestane for HR+/HER2- breast cancer or alone for other mTOR-sensitive advanced tumors, to see if it's safe and how your body handles it.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sapu Nano (Us) LLC (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Adelaide)
• Trial ID: NCT07369505 on ClinicalTrials.gov

What this trial studies

This open-label phase 1b dose-escalation protocol gives weekly 30-minute IV infusions of Sapu003 at planned dose levels of 5, 7.5, and 10 mg/m² in 28-day cycles to identify the maximum tolerated dose. Cohort A enrolls postmenopausal women with HR+/HER2- advanced breast cancer who receive Sapu003 plus oral exemestane; Cohort B enrolls adults with RCC, NETs, TSC-associated tumors, or HCC who receive Sapu003 alone. The primary goal is to characterize safety, tolerability and the MTD, with secondary objectives including pharmacokinetics and preliminary antitumor activity. Participants will be monitored for adverse events, drug levels, and tumor response throughout treatment.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced mTOR-sensitive solid tumors—postmenopausal women with HR+/HER2- metastatic breast cancer who have progressed on endocrine therapy for Cohort A, and adults with advanced RCC, NETs, TSC-associated tumors, or HCC for Cohort B.

Not a fit: Patients whose cancers are not driven by mTOR signaling, those unable to tolerate weekly IV infusions, or those with poor organ function or very limited life expectancy are unlikely to benefit.

Why it matters

Potential benefit: If successful, this approach could provide a new IV mTOR-targeting treatment option and dosing strategy for patients with mTOR-sensitive tumors who have progressed on existing therapies.

How similar studies have performed: Oral mTOR inhibitors such as everolimus have shown clinical benefit in HR+ breast cancer and some other mTOR-driven tumors, but weekly IV Sapu003 is a novel formulation and requires early-phase testing to confirm safety and activity.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. 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.
3. 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
     * Hepatocellular Carcinoma (HCC)
   * Has disease that is measurable and/or evaluable per RECIST v1.1 (or relevant criteria, if applicable).
   * Has progressed on or is intolerant to at least one prior line of standard therapy appropriate for the specific tumor type, unless no effective standard therapy exists.
   * Has agreed to participate in the study and signed the informed consent form prior to participation in any study activities.
4. Patients must be on stable doses of metformin or statin
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
6. Life expectancy ≥ 3 months
7. Hematology/chemistry: Patient has adequate hematological, renal, and hepatic function as defined by the following Screening laboratory values obtained within 7 days prior to randomization and assessed based on local labs (patients should not have received a transfusion within 7 days before the Screening laboratory assessments):

   * Absolute neutrophil count (ANC) ≥ 2,000 cells/mm3 (2 x109/L)
   * Platelet count ≥ 100,000 cells/mm3 (100x109/L)
   * Hemoglobin≥ 9 g/dL
   * Serum creatinine≤ 1.5 x the upper limit of normal (ULN)
   * Total bilirubin ≤1.5 x ULN or direct bilirubin ≤1 x ULN for patients with total bilirubin levels \> 1.5 ULN
   * AST (SGOT) / ALT (SGPT) ≤ 2.5 x ULN (≤5 x ULN for patients with metastases.)
   * GFR ≥ 50 mL/min/1.73m2 by the CKD-EPI or MDRD formulas.
8. All other clinical laboratory values deemed as normal or not clinically significant by the Principal Investigator/Sub-Investigator.
9. Breastfeeding: Patients must be non-lactating. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding must be discontinued prior to the first dose of study drug.
10. Female patients of reproductive potential to avoid becoming pregnant and to use effective contraception during the study and for 8 weeks after the last dose. Male patients with female partners of reproductive potential to use effective contraception during the study and for 4 weeks after the last dose.
11. Able and willing to adhere to all protocol requirements and study procedures throughout the course of the study.
12. Ability to comprehend and be informed of the nature of the study, as assessed by study clinic staff

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Patients had major surgery within 30 days prior to randomization, or patients have not recovered from prior major surgery.
5. Sensory / Peripheral neuropathy of \> Grade 1 per NCI CTCAE version 5.0 at Screening.
6. 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.
7. 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).
8. History of difficulty with donating blood or difficulty in accessibility of central line.
9. 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);
   * Hypersensitivity or idiosyncratic reaction to everolimus, other rapamycin derivatives or its excipients
   * Severe allergic reactions (e.g., anaphylactic reactions, angioedema).
10. Patients may not participate in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or the use of investigational devices with therapeutic intent within 30 days prior to randomization and while enrolled in this study. Caution is recommended when administering Sapu003 and concomitantly with known substrates, PgP inhibitors, inhibitors, and inducers of the cytochrome P450 isoenzymes CYP2C8 and CYP3A4.
11. Use of any strong inhibitors of cytochrome P450 (CYP) enzymes (e.g., fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (e.g., barbiturates (phenobarbital), carbamazepine, phenytoin and rifampin), in the previous 14 days before randomization until the last blood draw in the study.
12. Acute active infection requiring antibiotics, antiviral agents, or antifungal agents within 14 days prior to randomization
13. Pregnant or lactating women.

Where this trial is running

Adelaide

• Socru — Adelaide, Australia (Recruiting)

Study contacts

• Study coordinator: Cynthia Lee

Conditions Breast Cancer Metastatic; Renal Cell Carcinoma; Neuroendocrine Tumors; Tuberous Sclerosis Complex; Hepatocellular Carcinoma; Sapu003; Everolimus for Injection; mTOR-Sensitive Solid Tumors