Evaluating QBS72S for treating brain metastases in cancer patients

Phase IIa Study Assessing QBS72S For Treating Brain Metastases

This study is testing a new treatment called QBS72S to see if it can help cancer patients whose cancer has spread to their brains feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Stanford University (Academic / other)
• Drugs / interventions: atezolizumab, pembrolizumab, bevacizumab, natalizumab, nivolumab, ocrelizumab, tofacitinib, chemotherapy
• Locations: 1 site (Palo Alto, California)
• Trial ID: NCT05305365 on ClinicalTrials.gov

What this trial studies

This study evaluates the efficacy and safety of QBS72S in patients with advanced, relapsed metastatic cancer that has spread to the central nervous system. The primary objective is to assess the overall response rate of QBS72S in patients with brain metastases from breast cancer or lung cancer. Secondary objectives include measuring progression-free survival, overall survival, and duration of response, as well as evaluating the safety of the treatment across different cohorts. Participants will be monitored for their response to the treatment and any adverse effects.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed breast or lung cancer that has metastasized to the brain after prior chemotherapy.

Not a fit: Patients with brain metastases who have not undergone prior chemotherapy or those with a Karnofsky Performance Status below 60 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with brain metastases from various cancers.

How similar studies have performed: Other studies have shown promise in treating brain metastases with targeted therapies, but the specific approach with QBS72S is novel.

Eligibility 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.

Where this trial is running

Palo Alto, California

• Stanford Cancer Institute — Palo Alto, California, United States (Recruiting)

Study contacts

• Principal investigator: Melanie H Gephart, MD, MAS — Stanford University
• Study coordinator: Brandon Carlson-Clarke

Conditions Brain Metastases; Breast Cancer; Lung Cancer; Leptomeningeal Disease; LMD