QBS72S for Brain Cancer from Breast Cancer

Overseen By Sahara Rout

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Melanie Hayden Gephart

Must not be taking: Live vaccines, EIAEDs

Disqualifiers: Active malignancy, Allergic reactions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 6 months

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called QBS72S for people with advanced breast cancer that has spread to the brain. The goal is to see if this drug can shrink brain tumors and help patients live longer. Researchers are also checking if the drug is safe for these patients.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for some drugs before starting. You may need to stop certain medications like small molecules, non-cytotoxic drugs, and others for a specific time before joining. Check with the trial team to see if your current medications are affected.

What makes the drug QBS72S unique for treating brain cancer from breast cancer?

QBS72S is unique because it is designed to penetrate the blood-brain barrier (a protective shield around the brain that blocks many drugs), which is a major challenge in treating brain metastases from breast cancer. This ability may allow it to effectively target and treat cancer cells in the brain, unlike many other treatments that struggle to reach these areas. ^{1 2 3 4 5}

Research Team

Melanie H Gephart, MD, MAS

Principal Investigator

Stanford University

Eligibility Criteria

Adults with advanced breast cancer that has spread to the brain, who've had prior chemotherapy. They must be able to consent, follow study procedures, and have good organ function and performance status. Contraception is required for those who can conceive. Exclusions include recent major surgery, certain medical conditions or treatments, high steroid doses, severe drug allergies, other active cancers within 3 years (except some skin cancers), pregnancy/breastfeeding.

Inclusion Criteria

Participant must have completed washout from prior therapy as applicable

My bone marrow is functioning well.

I meet the requirements for corticosteroid and anticonvulsant use.

Exclusion Criteria

I have no active cancer other than my primary diagnosis, except for treated skin cancer or carcinoma in situ.

I am currently using, or might need, medications that are not allowed in the trial.

Participants with intolerance or severe allergic reactions to specific substances in the investigational product

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive QBS72S IV injections once monthly until disease progression

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 months

1 visit (in-person)

Treatment Details

Interventions

• QBS72S

Trial Overview The trial tests QBS72S's effectiveness and safety in treating brain metastases from breast cancer. Participants will receive this investigational drug after completing previous treatments including chemo and radiotherapy as per specified waiting periods.

Participant Groups

Group I: Patients with any Primary Cancer Leptomeningeal Disease (Cohort 3) Experimental Treatment 1 Intervention

All participants in Cohort 3 will receive QBS72S IV injections once monthly until disease progression.

Group II: Patients with Breast Cancer Parenchymal brain metastasis (Cohort 1) Experimental Treatment 1 Intervention

All participants in Cohort 1 will receive QBS72S IV injections once monthly until disease progression.

Group III: Patients with Breast Cancer Leptomeningeal Disease (Cohort 2) Experimental Treatment 1 Intervention

All participants in Cohort 2 will receive QBS72S IV injections once monthly until disease progression.

Who Is Running the Clinical Trial?

Melanie Hayden Gephart

Lead Sponsor

Trials

1

Recruited

40+

Quadriga Biosciences, Inc.

Industry Sponsor

Trials

3

Recruited

520+

Findings from Research

In a study of 473 patients with metastatic breast cancer, 15.6% developed central nervous system (CNS) metastases, with a median survival of 7.53 months after diagnosis.

The risk of developing CNS metastases was notably higher in patients with aggressive breast cancer subtypes, particularly grade 3, hormone receptor-negative, HER2-positive cancers, while HER2-positive patients had better survival outcomes compared to those without locoregional treatment or with multiple CNS lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors and survival outcomes in patients with brain metastases from breast cancer. Minisini, AM., Moroso, S., Gerratana, L., et al.[2022]

The glycoprotein pMQ1 is commonly found in breast cancer tissues but absent in normal and benign breast tissues, indicating its potential role as a tumor marker.

Higher levels of pMQ1 are associated with worse outcomes, including higher histological grades and increased likelihood of local recurrence, suggesting it may serve as a prognostic indicator in breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic significance of glycoprotein pMQ1 in breast cancer. Fon, LJ., Lioe, TF., Mulligan, KA., et al.[2006]

DZD1516 is a promising HER2 inhibitor that effectively penetrates the blood-brain barrier and shows selectivity for HER2 over wild-type EGFR, making it a potential treatment for HER2-positive metastatic breast cancer with CNS metastases.

In a phase 1 trial involving 23 patients, DZD1516 demonstrated a maximum tolerated dose of 250 mg twice daily, with manageable side effects and stable disease as the best antitumor response, indicating its potential for further clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical and clinical activity of DZD1516, a full blood-brain barrier-penetrant, highly selective HER2 inhibitor. Zhang, J., McAndrew, NP., Wang, X., et al.[2023]

A novel screening method identified two compounds, Ch-1 and Ch-2, that effectively reduced brain tumor burden and increased survival by over 10 days in a mouse model of breast cancer metastasis to the brain.

Ch-1 works by preventing the activation of pro-survival pathways in cancer cells, suggesting a specific mechanism of action that could enhance treatment efficacy against brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Novel Agents for the Treatment of Brain Metastases of Breast Cancer. Venishetty, VK., Geldenhuys, WJ., Terell-Hall, TB., et al.[2018]

Trastuzumab has significantly improved treatment outcomes for advanced breast cancer patients with tumors that overexpress the ErbB2 (HER2) protein, but it has also led to an increased incidence of brain metastases in these patients.

Lapatinib, a targeted therapy that inhibits ErbB1 and ErbB2, shows promise as a potential treatment option for managing brain metastases in patients with ErbB2-positive breast cancer, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New challenges and opportunities in the management of brain metastases in patients with ErbB2-positive metastatic breast cancer. Melisko, ME., Glantz, M., Rugo, HS.[2018]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Risk factors and survival outcomes in patients with brain metastases from breast cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Prognostic significance of glycoprotein pMQ1 in breast cancer. [2006]

3. England pubmed.ncbi.nlm.nih.gov

Preclinical and clinical activity of DZD1516, a full blood-brain barrier-penetrant, highly selective HER2 inhibitor. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Identification of Novel Agents for the Treatment of Brain Metastases of Breast Cancer. [2018]

5. England pubmed.ncbi.nlm.nih.gov

New challenges and opportunities in the management of brain metastases in patients with ErbB2-positive metastatic breast cancer. [2018]