Study Assessing QBS72S For Treating Brain Metastases of Breast Cancer

Study Overview
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Brief Summary
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This study is to evaluate the efficacy and safety of QBS72S in participants with advanced, relapsed, metastatic breast cancer with CNS involvement.

Detailed Description
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Primary Objective 1. Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through overall response rate (ORR) in Cohort 1 (Stages 1+2). Secondary Objectives Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through progression free survival (PFS) in Cohort 1 (Stages 1+2). Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through overall survival (OS) in Cohort 1 (Stages 1+2). Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through durations of response (DoR) in Cohort 1 (Stages 1+2). Evaluate safety of QBS72S treatment in Cohort 1 (Stages 1+2), and Cohort 2.

Official Title
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A Phase IIa Study Assessing QBS72S For Treating Brain Metastases of Breast Cancer

Conditions
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Brain Metastases, Breast Cancer

Intervention / Treatment
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* Drug: QBS72S


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant must have a histologically-confirmed breast cancer primary tumor, either confirmed via primary specimen or via metastasis site, having developed brain metastases (parenchymal or LM) after a prior cytotoxic chemotherapy regimen. There is no restriction on prior cycles of systemic therapy for metastatic breast cancer One of the following: A participant with brain parenchymal tumors must have at least one untreated tumor > 3 mm2 that can be seen on 2 or more separate acquired sequences. A participant with LM disease must have a positive cytology or MRI evidence of LMD. The presence of parenchymal brain metastases does not exclude these participants from Cohort 2. The participant must be 18 years old or older. The participant must have a Karnofsky Performance Status (KPS) of 60 or above. The participant must receive an MRI with contrast that supports the presence of parenchymal brain metastases or leptomeningeal disease. The participant must be on stable doses of corticosteroids and anticonvulsants for greater than or equal to 5 days prior to obtaining the baseline Gd-MRI of the brain. The participant must have completed treatment greater than or equal to: 14 days for small molecules and non-cytotoxic systemic drugs e.g., PARP inhibitors 21 days for checkpoint inhibitors and monoclonal antibodies, e.g., atezolizumab, pembrolizumab, and bevacizumab, and cytotoxic chemotherapy 28 days for investigational drugs and radiotherapy; or 1 dosing cycle for other interventions, prior to first dose of QBS72S All clinically significant toxicities excluding alopecia must have resolved to less than or equal to CTCAE v5.0 Grade 1. Participation in long term follow up is allowed if no procedures will be performed which may interfere with the interpretation of study results. The participant must have adequate bone marrow function, including: ANC ≥ 1,500/mm3 or ≥ 1.5 x 109/L Platelets ≥ 100,000/ mm3 or ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL The participant must have adequate renal function, including serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min. In equivocal cases, a 24-hour urine collection test can be used to estimate the creatinine clearance more accurately. The participant must have adequate liver function, including: Total serum bilirubin ≤ 1.5 x ULN unless the participant has documented Gilbert syndrome who must have a total bilirubin < 3.0 mg/dl Aspartate and Alanine aminotransferase (AST and ALT) ≤ 2.5 x ULN; ≤ 5.0 x ULN if there is liver involvement by the tumor Any participant physiologically capable of becoming pregnant or getting a partner pregnant must agree to use highly effective contraception during study treatment and for 7 months after study discontinuation. Participants or their designated advocates must be willing to and capable of providing informed consent and willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. Exclusion Criteria: Participants currently using any anticancer therapy (including radiotherapy) or using any investigational agent(s), except those explicitly documented allowable by the PI. Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ. Participants taking a dexamethasone dose greater than 8 mg per day as a stable or decreasing dose. No escalation of dexamethasone dosing is allowed in the past 14 days prior to screening. Participants who received major surgery or brain surgery within 28 days or fewer. Minor procedures such as tumor biopsy are allowed with written approval of the PI. Participants with intolerance to or who have had a severe (Grade 3) allergic or anaphylactic reaction to any of the substances included in the investigational product: sulfobutylether-β-cyclodextrin, melphalan, bendamustine, chlorambucil or any nitrogen mustard chemotherapeutics. Participants who currently use or have an anticipated need for a contraindicated medication including live vaccines, natalizumab, nivolumab, ocrelizumab, palifermin, pimecrolimus, tacrolimus, tofacitinib, and EIAEDs, including phenytoin, phenobarbital, carbamazepine, fosphenytoin, primidone, and oxcarbazepine. The washout period for any live vaccine is 30 days prior to enrollment. There is no restriction for seasonal flu vaccines that do not contain live virus, nor any approved COVID vaccine. Participants who are pregnant or breastfeeding. Participants who have active medical or psychiatric conditions which, in the opinion of the Principal Investigator or a Sub-Investigator, would compromise or interfere with their ability to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QBS72S 12 mg/m2 IV injection<br>All participants will receive QBS72S IV injections once monthly until disease progression. | Drug: QBS72S<br>* QBS72S 12mg/m2 injection given intravenous once a month.<br>* Other names: QBS10072S;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response against Intracranial Tumor Lesions | The overall response against the target intracranial tumor lesions in Cohort 1 (Stages 1+2) participants was assessed by according to the modified Response Assessment in Neuro-oncology for Brain Metastases (mRANO-BM) | 6 months | 
| RECIST 1.1 response criteria | Clinical response means either a complete response (CR) or a partial response (PR). CR is defined as disappearance of tumor lesions, and PR is defined as ≥ 30% reduction in diameter of tumor lesions. | 6 months from the start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Progression-free Survival (PFS) means to remain alive without tumor progression, assessed as a ≥ 25% increase in tumor diameter | 2 months | 
| Overall Survival (OS) | Overall survival (OS) refers to remaining alive at the time of the assessment. | 2 months | 
| Duration of Response (DoR) | Duration of Response (DoR) refers to length of time that a clinical response is maintained in Cohort 1 (Stages 1+2) participants. | 6 months | 
| Related Adverse Events (AEs) |  | 30 days following the last administration of study drug |