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Trial registered on ANZCTR


Registration number
ACTRN12625001083482
Ethics application status
Approved
Date submitted
16/09/2025
Date registered
3/10/2025
Date last updated
3/10/2025
Date data sharing statement initially provided
3/10/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Sapu003 in Combination with Exemestane in Post-Menopausal Women with HR+, HER2-Negative Advanced or Metastatic Breast Cancer
Scientific title
A Phase 1b, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics of Sapu003 in Combination with Exemestane in Post-Menopausal Women with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer After Progression on a Non-Steroidal Aromatase Inhibitor.
Secondary ID [1] 315390 0
SP-03-B101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 338894 0
Condition category
Condition code
Cancer 335188 335188 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The investigational intervention consists of Sapu003 (Everolimus) for Injection, administered intravenously over 30 minutes once weekly in 4-week (28-day) cycles. Dose escalation will follow the Bayesian Optimal Interval (BOIN) design to determine the Maximum Tolerated Dose (MTD), with planned dose levels of 5 mg/m², 7.5 mg/m², and 10 mg/m², and an optional –1 cohort at 3.5 mg/m² if required for safety. Treatment will continue for up to 6 months or until disease progression, unacceptable toxicity, or withdrawal of consent. Dose escalation/de-escalation decisions will be made at the end of each cohort based on the Bayesian Optimal Interval (BOIN) design.

Separate cohorts of patients are enrolled at each dose level. All patients at a given dose level must complete one full cycle (4 weekly infusions) before the next cohort at the higher dose can be enrolled.

Sapu003 will be reconstituted in 0.9% Sodium Chloride Injection, USP (4 mg/mL), diluted in 250 mL 0.9% Sodium Chloride, stored at 2–8°C, protected from light, and administered using amber-covered IV tubing.

All participants will also receive exemestane 25 mg orally once daily throughout the study, administered continuously in combination with Sapu003 until disease progression, unacceptable toxicity, or withdrawal of consent. Exemestane is a steroidal aromatase inhibitor that irreversibly suppresses estrogen synthesis and represents the standard of care for HR+/HER2- advanced breast cancer after progression on non-steroidal aromatase inhibitors. Participants must also be on stable doses of metformin or statins prior to enrollment, as these agents are expected to provide synergistic effects by modulating mTOR signaling and tumor metabolism. Supportive medications, including antiemetics and G-CSF for neutropenia, are permitted.

Adherence to the Exemestane doses is assessed indirectly through patient reporting and documentation of concomitant medications at study visits.
Intervention code [1] 332001 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 342804 0
Determine the maximum tolerated dose (MTD) of Sapu003 in combination with exemestane
Timepoint [1] 342804 0
Weekly thoughout Cycle 1 (first 4 weeks; 28-day cycle)
Secondary outcome [1] 452188 0
Characterize the pharmacokinetic profile of weekly IV Sapu003 co-administered with exemestane 25 mg QD
Timepoint [1] 452188 0
Week 1 of Cycles 1 and 2 only at: Pre-dose, End of infusion, 1, 2, 4, 6, 8, 24, 48, and 72 hours post-infusion
Secondary outcome [2] 452189 0
Characterize the safety and tolerability profile of Sapu003 - Comopsite outcome
Timepoint [2] 452189 0
Baseline, weekly prior to dosing, and at end-of-study (up to 6 months) or early withdrawal due to progressive disease or unacceptable toxicity to the treatment.
Secondary outcome [3] 452190 0
Describe preliminary anti-tumor activity (Objective Response Rate (ORR), Disease Control Rate (DCR), Progression-Free Survival (PFS), Duration of Response (DoR), Overall Survival (OS)) - composite secondary outcome.
Timepoint [3] 452190 0
Baseline, every 8 weeks during treatment, and every 12 weeks after treatment discontinuation until documented disease progression.

Eligibility
Key inclusion criteria
1. Sex and Age: Postmenopausal women; defined as those 18 years of age or older exhibiting amenorrhea for more than or equal to 12 consecutive months without another pathophysiological cause
2. Female breast cancer patient who:
• Has histologically or cytologically documented advanced (metastatic or unresctable) 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. Patients must be on stable doses of metformin or statin
4. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
5. Life expectancy more than or equal to 3 months
6. 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) more than or equal to 2,000 cells/mm3 (2 x109/L)
• Platelet count more than or equal to 100,000 cells/mm3 (100x109/L)
• Hemoglobin more than or equal to 9 g/dL
• Serum creatinine less than or equal to 1.5 x the upper limit of normal (ULN)
• Total bilirubin less than or equal to 1.5 x ULN or direct bilirubin less than or equal to 1 x ULN for patients with total bilirubin levels > 1.5 ULN
• AST (SGOT) / ALT (SGPT) less than or equal to 2.5 x ULN (less than or equal to 5 x ULN for patients with metastases.)
• GFR more than or equal to 50 mL/min/1.73m2 by the CKD-EPI or MDRD formulas.
7. All other clinical laboratory values deemed as normal or not clinically significant by the Principal Investigator/Sub-Investigator.
8. This study enrolls only post-menopausal women, defined as those who have not experienced a menstrual period for at least 52 weeks or who have undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, bilateral tubal ligation). However, women who do not clearly meet these post-menopausal criteria will be excluded to ensure the study population is limited to non-childbearing participants.
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. Able and willing to adhere to all protocol requirements and study procedures throughout the course of the study.
11. Ability to comprehend and be informed of the nature of the study, as assessed by study clinic staff
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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 more than 5 years.
2. Patients who have not completely recovered from any toxicities from previous chemotherapy, hormone therapy, immunotherapy, or radiotherapies more than or equal to 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, 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. Patient had major surgery within 30 days prior to randomization, or patient has not recovered from prior major surgery.
5. Sensory / Peripheral neuropathy of more than 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
3/11/2025
Actual
Date of last participant enrolment
Anticipated
3/11/2027
Actual
Date of last data collection
Anticipated
31/05/2028
Actual
Sample size
Target
27
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 319981 0
Commercial sector/Industry
Name [1] 319981 0
Ingenu CRO Pty. Ltd
Country [1] 319981 0
Australia
Funding source category [2] 319982 0
Commercial sector/Industry
Name [2] 319982 0
Sapu Bioscience, LLC
Country [2] 319982 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Ingenu CRO Pty. Ltd
Address
Country
Australia
Secondary sponsor category [1] 322508 0
Commercial sector/Industry
Name [1] 322508 0
Sapu Bioscience, LLC
Address [1] 322508 0
Country [1] 322508 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 318520 0
Bellberry Human Research Ethics Committee K
Ethics committee address [1] 318520 0
Ethics committee country [1] 318520 0
Australia
Date submitted for ethics approval [1] 318520 0
30/06/2025
Approval date [1] 318520 0
29/08/2025
Ethics approval number [1] 318520 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 144446 0
Dr Sem Liew
Address 144446 0
Vitalis Clinical Research, 456 St Kilda Rd, Melbourne VIC 3004
Country 144446 0
Australia
Phone 144446 0
+61 03 9041 7159
Fax 144446 0
Email 144446 0
[email protected]
Contact person for public queries
Name 144447 0
Darryl Davies
Address 144447 0
iNGENu CRO, Unit 22/456 St Kilda Rd, Melbourne VIC 3004
Country 144447 0
Australia
Phone 144447 0
+61 1300 030 380
Fax 144447 0
Email 144447 0
[email protected]
Contact person for scientific queries
Name 144448 0
Darryl Davies
Address 144448 0
iNGENu CRO, Unit 22/456 St Kilda Rd, Melbourne VIC 3004
Country 144448 0
Australia
Phone 144448 0
+61 1300 030 380
Fax 144448 0
Email 144448 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.