BL-M07D1 for HER2-Positive Cancer

Recruiting at 3 trial locations

Overseen By Whitney Eakins

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: SystImmune Inc.

Must not be taking: Chemotherapy, Immunotherapy, Antihypertensives, others

Disqualifiers: Severe heart disease, Autoimmune, CNS tumors, others

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

Compensation: Varies

Number of Visits: 3

280 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this study is to evaluate the safety, tolerability, and efficacy of BL-M07D1 in patients with HER2 expressing advanced tumors.

Will I have to stop taking my current medications?

The trial requires that you stop certain treatments like chemotherapy, biological therapy, and others at least 2 weeks before starting the study. If you're on medications for other conditions, the protocol doesn't specify, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug BL-M07D1 for HER2-positive cancer?

Research shows that treatments targeting HER2, like trastuzumab and lapatinib, have significantly improved outcomes for patients with HER2-positive breast cancer. New HER2-targeting drugs and combinations have led to better survival rates and long-term responses, suggesting that similar treatments could be effective. ^{1 2 3 4 5}

What makes the drug BL-M07D1 unique for treating HER2-Positive Cancer?

BL-M07D1 may involve targeting the B7 family of molecules, which are known to play a role in immune system regulation and tumor immunity. This approach could offer a novel mechanism by enhancing the body's immune response against cancer cells, potentially differing from standard treatments that do not focus on these pathways. ^{6 7 8 9 10}

Research Team

Clinical Leader

Principal Investigator

SystImmune Inc.

Eligibility Criteria

This trial is for adults with advanced tumors that express the HER2 protein, including cancers of the biliary tract, ovaries, cervix, endometrium, and bladder. Specific eligibility details are not provided but typically include health status and prior treatments.

Inclusion Criteria

My bladder cancer shows HER2 expression.

My endometrial cancer tests positive for HER2.

My cervical cancer is HER2 positive.

Exclusion Criteria

Participated in another clinical trial within 4 weeks or two half-lives (whichever is longer) prior to first dose of study treatment

I have been treated with topoisomerase 1 inhibitors.

I had another cancer but it has been in remission for the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive BL-M07D1 to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) over a 21-day cycle

21 days

1 visit (in-person) per cycle

Dose Finding

Participants receive BL-M07D1 to identify two or more recommended doses for dose expansion

21 days

1 visit (in-person) per cycle

Dose Expansion

Participants receive BL-M07D1 at the recommended dose to further evaluate safety and efficacy

21 days

1 visit (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• BL-M07D1

Trial Overview The study is testing BL-M07D1's safety and effectiveness in treating HER2-positive tumors. It's an open-label trial meaning everyone knows they're getting BL-M07D1; there's no placebo or comparison group.

Participant Groups

Group I: BL-M07D1 administered Day 1 of a 21-day cycle Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

SystImmune Inc.

Lead Sponsor

Trials

23

Recruited

1,800+

Findings from Research

Recent trials show that new HER2-targeted agents like pertuzumab and trastuzumab emtansine (T-DM1) are effective in treating HER2-positive breast cancer, with T-DM1 being a powerful combination of trastuzumab and a cytotoxic agent.

Combining trastuzumab with lapatinib or pertuzumab has led to significantly better outcomes, nearly doubling the rates of complete response in patients, indicating a shift towards dual anti-HER2 therapies to overcome resistance in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging strategies for the dual inhibition of HER2-positive breast cancer. Konecny, GE.[2019]

HER2-positive breast cancer, which makes up 15% to 20% of all breast cancers, has seen significant improvements in survival rates for metastatic patients due to the development of new anti-HER2 agents.

The ongoing advancements in targeted treatments and diagnostic tools aim to personalize therapy, potentially increasing cure rates while reducing the risk of overtreatment for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Moving Into a New Era. Gion, M., Trapani, D., Cortés, A., et al.[2022]

HER2-targeted therapies, such as trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1), have significantly improved survival rates for patients with HER2-positive breast cancer, both in early and advanced stages, without increasing toxicity.

Despite these advancements, resistance to HER2-targeted treatments is common, highlighting the need for further research into the mechanisms of resistance and the development of biomarkers to personalize therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updates on the treatment of human epidermal growth factor receptor type 2-positive breast cancer. Kim, M., Agarwal, S., Tripathy, D.[2020]

HER2-positive metastatic breast cancer is more aggressive and often develops resistance to treatments compared to HER2-negative tumors, making effective management crucial.

Trastuzumab is the standard treatment for HER2-positive cases, but lapatinib has been developed as a targeted therapy that works inside the cell to disrupt harmful signaling pathways, offering a potential solution to overcome resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming treatment challenges in advanced breast cancer. Harkins, B., Geyer, CE.[2018]

In a phase 3 trial involving 444 patients with HER2-positive breast cancer, traditional chemotherapy combined with HER2-targeted treatments (docetaxel, carboplatin, trastuzumab, and pertuzumab) resulted in a higher rate of pathological complete response (55.7%) compared to the targeted therapy alone (trastuzumab emtansine plus pertuzumab, 44.4%).

Patients receiving trastuzumab emtansine plus pertuzumab experienced significantly fewer severe adverse events (13% vs 64% for grade 3-4 events), suggesting that while traditional chemotherapy may be more effective, it also carries a higher risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Hurvitz, SA., Martin, M., Symmans, WF., et al.[2022]

A new fusion cell line, FLB2C, was created by fusing mouse lung cancer cells with active B lymphocytes, which successfully expressed both lung cancer antigens and the B7 molecule.

The oncogenicity of the FLB2C cells was significantly reduced, as they showed slower growth, no colony formation in soft agar, and did not form tumors when injected into mice, suggesting potential for developing improved lung cancer vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Establishment and growth characteristics of mouse lung cancer B₇ fusion cells]. Lin, P., Lu, Y., Zhang, J., et al.[2010]

B7DC, a member of the B7 family, enhances CD8 T cell-mediated rejection of tumor cells, indicating its potential role in boosting antitumor immunity during both the induction and effector phases.

B7DC can promote T cell killing through a mechanism that does not rely on PD-1, suggesting it has a unique pathway for enhancing tumor immunity that may clarify its previously observed dual functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism. Liu, X., Gao, JX., Wen, J., et al.[2022]

Doxorubicin was found to effectively reduce the surface expression of the immune checkpoint molecule B7-H1 in breast cancer cells, which may enhance the immune response against tumors.

The study revealed that B7-H1 not only plays a role in immune evasion but also has an anti-apoptotic function in breast cancer cells, suggesting that targeting B7-H1 alongside chemotherapy could improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxorubicin downregulates cell surface B7-H1 expression and upregulates its nuclear expression in breast cancer cells: role of B7-H1 as an anti-apoptotic molecule. Ghebeh, H., Lehe, C., Barhoush, E., et al.[2022]

The study identifies B7x as a factor that promotes tumor growth by interacting with myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment.

B7x may bind to a new receptor on MDSCs, potentially enhancing their proliferation and immunosuppressive abilities, which could contribute to the progression of tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7x and myeloid-derived suppressor cells in the tumor microenvironment: A tale of two cities. Jeon, H., Ohaegbulam, KC., Abadi, YM., et al.[2021]

The overexpression of the B7-H1 molecule (PDL-1) in various cancers is associated with poorer patient outcomes and resistance to cancer treatments, indicating its role as a negative prognostic factor.

The review discusses mechanisms by which B7-H1 inhibits the immune response against cancer cells and suggests potential therapeutic strategies to target this molecule, which could improve cancer treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The immunoinhibitory B7-H1 molecule as a potential target in cancer: killing many birds with one stone. Afreen, S., Dermime, S.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Emerging strategies for the dual inhibition of HER2-positive breast cancer. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Moving Into a New Era. [2022]

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

Updates on the treatment of human epidermal growth factor receptor type 2-positive breast cancer. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Overcoming treatment challenges in advanced breast cancer. [2018]

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

Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. [2022]

6. China pubmed.ncbi.nlm.nih.gov

[Establishment and growth characteristics of mouse lung cancer B₇ fusion cells]. [2010]

7. United States pubmed.ncbi.nlm.nih.gov

B7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Doxorubicin downregulates cell surface B7-H1 expression and upregulates its nuclear expression in breast cancer cells: role of B7-H1 as an anti-apoptotic molecule. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

B7x and myeloid-derived suppressor cells in the tumor microenvironment: A tale of two cities. [2021]

10. Saudi Arabia pubmed.ncbi.nlm.nih.gov

The immunoinhibitory B7-H1 molecule as a potential target in cancer: killing many birds with one stone. [2022]