Study Assessing QBS72S For Treating Brain Metastases

• ClinicalTrials.gov Identifier: NCT05305365
• Recruitment Status: Recruiting
• First Posted: March 31, 2022
• Last Update Posted: February 23, 2024
• Sponsor: Melanie Hayden Gephart
• Collaborator: Quadriga Biosciences, Inc.
• Information provided by (Responsible Party): Melanie Hayden Gephart, Stanford University

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Brain Metastases; Breast Cancer	Drug: QBS72S	Phase 2

Detailed Description:

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

1. Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through progression free survival (PFS) in Cohort 1 (Stages 1+2).
2. Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through overall survival (OS) in Cohort 1 (Stages 1+2).
3. Test of the preliminary efficacy of the intracranial anti tumor activity of QBS72S through durations of response (DoR) in Cohort 1 (Stages 1+2).
4. Evaluate safety of QBS72S treatment in Cohort 1 (Stages 1+2), Cohort 2, and Cohort 3.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase IIa Study Assessing QBS72S For Treating Brain Metastases
• Actual Study Start Date: August 16, 2022
• Estimated Primary Completion Date: February 2025
• Estimated Study Completion Date: August 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Patients with Breast Cancer Parenchymal brain metastasis (Cohort 1); All participants in Cohort 1 will receive QBS72S IV injections once monthly until disease progression.	Drug: QBS72S; QBS72S 18mg/m2 injection given intravenous once a month.; Other Name: QBS10072S
Experimental: Patients with Breast Cancer Leptomeningeal Disease (Cohort 2); All participants in Cohort 2 will receive QBS72S IV injections once monthly until disease progression.	Drug: QBS72S; QBS72S 18mg/m2 injection given intravenous once a month.; Other Name: QBS10072S
Experimental: Patients with any Primary Cancer Leptomeningeal Disease (Cohort 3); All participants in Cohort 3 will receive QBS72S IV injections once monthly until disease progression.	Drug: QBS72S; QBS72S 18mg/m2 injection given intravenous once a month.; Other Name: QBS10072S

Outcome Measures

Primary Outcome Measures :

1. Overall Response against Intracranial Tumor Lesions, Cohort 1 (Stages 1+2) [ Time Frame: 6 months ]
   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)
2. RECIST 1.1 response criteria [ Time Frame: 6 months from the start of treatment ]
   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.

Secondary Outcome Measures :

1. Progression-free Survival (PFS), Cohort 1 (Stages 1+2) [ Time Frame: 2 months ]
   Progression-free Survival (PFS) means to remain alive without tumor progression, assessed as a ≥ 25% increase in tumor diameter
2. Overall Survival (OS), Cohort 1 (Stages 1+2) [ Time Frame: 2 months ]
   Overall survival (OS) refers to remaining alive at the time of the assessment.
3. Duration of Response (DoR), Cohort 1 (Stages 1+2) [ Time Frame: 6 months ]
   Duration of Response (DoR) refers to length of time that a clinical response is maintained in Cohort 1 (Stages 1+2) participants.
4. Related Adverse Events (AEs) [ Time Frame: 30 days following the last administration of study drug ]
   Toxicity refers to drug-related adverse events (AEs). The outcome is reported as the number of related AEs that were serious or non-serious, and by severity (mild, moderate, severe, life-threatening, or fatal), numbers without dispersion

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. The participant must be 18 years or older
2. The participant must have a Karnofsky Performance Status (KPS) of 60 or above.

3. One of the following:

   1. Cohorts 1 and 2: 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 LMD) after a prior cytotoxic chemotherapy regimen.
   2. Cohort 3: The participant must have a histologically cancerous primary tumor, either confirmed via primary specimen or via metastasis site, having developed brain metastases (parenchymal or LMD) after a prior cytotoxic chemotherapy regimen. There is no restriction on prior cycles of systemic therapy for any primary cancer type. Breast cancer is not excluded from Cohort 3.

4. One of the following:

   1. Cohort 1: A participant with breast cancer brain parenchymal tumors must have at least one nonirradiated tumor ≥ 3 mm2 that can be seen on 2 or more separate acquired brain MRI sequences.
   2. Cohort 2: A participant with breast cancer primary and

   LMD must receive either:

   i. a brain MRI with contrast that supports the presence of LMD, or ii. a CSF cytology test that is either positive for or suspicious for malignancy. The presence of parenchymal brain metastases does not exclude these participants from Cohort 2.

   a. Cohort 3: A participant with LMD from any primary cancer site must receive either: i. a brain MRI with contrast that supports the presence of LMD, or ii. a CSF cytology test that is either positive for or suspicious for malignancy. The presence of parenchymal brain metastases does not exclude these participants from Cohort 3.

5. For corticosteroids and anticonvulsants, the participant must either: c. not be taking any, or d. be taking stable or decreasing doses for ≥5 days prior to obtaining the screening Gd-MRI of the brain. The maximum allowable dose of corticosteroids is 8mg of dexamethasone per day, or the equivalent of another medication as assessed by a Neuro-Oncologist. Escalation of corticosteroids is not allowed ≤14 days prior to C1D1.
6. The participant must have completed washout from prior therapy before C1D1, as applicable: e. ≥7 days for Ommaya placement (Cohorts 2+3) f. ≥14 days for small molecules and non-cytotoxic systemic drugs e.g., PARP inhibitors g. ≥21 days for checkpoint inhibitors and monoclonal antibodies, e.g., atezolizumab, pembrolizumab, and bevacizumab, and cytotoxic chemotherapy h. ≥28 days for investigational drugs, radiotherapy, and major surgery. Minor procedures such as tumor biopsy are allowed with written approval from the PI i. ≥1 dosing cycle for other interventions All significant toxicities from previous anticancer therapy must have stabilized to a new baseline or have resolved. Participation in long term follow up in another clinical trial is allowed if no procedures will be performed which may interfere with the interpretation of study results.
7. The participant must have adequate bone marrow function, including: j. ANC ≥ 1,500/mm3 or ≥ 1.5 x 109/L k. Platelets ≥ 100,000/ mm3 or ≥ 100 x 109/L l. Hemoglobin ≥ 9 g/dL
8. 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.
9. The participant must have adequate liver function, including: m. Total serum bilirubin ≤ 1.5 x ULN unless the participant has documented Gilbert syndrome who must have a total bilirubin < 3.0 mg/dl n. Aspartate and Alanine aminotransferase (AST and ALT) ≤ 2.5 x ULN; ≤ 5.0 x ULN if there is liver involvement by the tumor
10. 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.
11. 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

1. Participants with any other current, active malignancy unrelated to their primary cancer diagnosis, except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ.
2. 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.
3. 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.
4. Participants who are pregnant or breastfeeding.
5. 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.

Contacts and Locations

Contacts

Contact: Kriti Lalwani; 650-736-6489; kritil@stanford.edu

Contact: Monica Granucci; 650-388-8906; migranucci@stanford.edu

Locations

United States, California

Stanford Cancer Institute; Recruiting

Palo Alto, California, United States, 94305

Contact: Monica Granucci 650-388-8906 migranucci@stanford.edu

Principal Investigator: Melanie H Gephart, MD, MAS

Sub-Investigator: Michael Iv, MD

Sub-Investigator: Seema Nagpal, MD

Sub-Investigator: Michael Lim, MD

Sub-Investigator: Gordon Li, MD

Sub-Investigator: Steven Chang, MD

Sub-Investigator: Lawrence Shuer, MD

Sub-Investigator: Reena Thomas, MD

Sub-Investigator: Chirag Patel, MD

Sub-Investigator: Melinda Telli, MD

Sub-Investigator: Michelle Melisko, MD

Sponsors and Collaborators

Melanie Hayden Gephart

Quadriga Biosciences, Inc.

Investigators

• Principal Investigator: Melanie H Gephart, MD, MAS; Stanford University

More Information

• Responsible Party: Melanie Hayden Gephart, Professor of Neurosurgery, Stanford University
• ClinicalTrials.gov Identifier: NCT05305365
• Other Study ID Numbers: IRB-63041; BRN0051 ( Other Identifier: OnCore ); NCI-2023-00648 ( Other Identifier: CTRP )
• First Posted: March 31, 2022
• Last Update Posted: February 23, 2024
• Last Verified: February 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasm Metastasis; Brain Neoplasms; Neoplastic Processes; Neoplasms; Pathologic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases