BL-M07D1 for HER2-Positive Cancer

Recruiting at 17 trial locations

Overseen By Christine LaRock

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests BL-M07D1, a new treatment for people with advanced tumors that have the HER2 protein. The main aim is to assess its safety, tolerability, and effectiveness against cancer. Different groups in the trial help determine the right dose and its effects on various cancers, such as breast, lung, and stomach. It suits those who have tried other treatments, are not candidates for surgery or radiation, and have HER2-positive cancer. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

Is there any evidence suggesting that BL-M07D1 is likely to be safe for humans?

Research has shown that BL-M07D1 was safe in earlier studies. For patients with HER2-positive breast cancer, the treatment was generally well-tolerated, with most experiencing no serious side effects. Earlier research also indicated that the treatment did not cause unexpected issues, and any side effects were manageable. For those considering joining a trial with BL-M07D1, this information suggests it could be a safe option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about BL-M07D1 for HER2-positive cancer because it offers a potentially novel mechanism of action compared to existing treatments like trastuzumab or pertuzumab. Unlike these standard therapies that target HER2 receptors on cancer cells, BL-M07D1 may involve a unique approach in binding or impacting these cells, possibly leading to improved outcomes. Additionally, the treatment is administered via intravenous infusion every three weeks, which could provide a convenient schedule for patients. This innovative approach has the potential to enhance effectiveness and offer a new option for those who may not respond well to current therapies.

What evidence suggests that BL-M07D1 might be an effective treatment for HER2-positive cancer?

Research has shown that BL-M07D1, a new treatment, offers promising results for patients with HER2-positive cancers. In earlier studies, BL-M07D1 proved effective, particularly for patients who had exhausted many treatments for HER2-positive breast cancer. This trial will explore various dosing strategies of BL-M07D1, including dose escalation, dose finding, and dose expansion. The drug combines a special protein with a cancer-fighting medicine, targeting and killing cancer cells while sparing healthy cells. These early findings provide hope for its potential success in treating HER2-positive cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Clinical Leader

Principal Investigator

SystImmune Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Experimental: Dose Finding Experimental Treatment 1 Intervention

Beginning with Cycle 1, BL-M07D1 will be administered on Day 1 by (IV) infusion every 3 weeks (D1Q3W)

Group II: Experimental: Dose Expansion Experimental Treatment 1 Intervention

Beginning with Cycle 1, BL-M07D1 will be administered on Day 1 by (IV) infusion every 3 weeks (D1Q3W)

Group III: Experimental: Dose Escalation Experimental Treatment 1 Intervention

Beginning with Cycle 1, BL-M07D1 will be administered on Day 1 by (IV) infusion every 3 weeks (D1Q3W)

Who Is Running the Clinical Trial?

SystImmune Inc.

Lead Sponsor

Trials

23

Recruited

1,800+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/PO2-04-03/744341/Abstract-PO2-04-03-BL-M07D1-an-antibody-drug

Abstract PO2-04-03: BL-M07D1, an antibody-drug conjugate ... Conclusions: BL-M07D1 demonstrated encouraging efficacy in heavily pretreated HER2 expressing cancers, especially in HER2+ BC. The safety ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05461768

NCT05461768 | A Study of BL-M07D1 in Patients With ... In phase Ia study, the safety and tolerability of BL-B07D1 in patients with locally advanced or metastatic HER2-positive/low-expression breast cancer and ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02708-4/fulltext

685P BL-M07D1, a HER2 antibody-drug conjugate in ... Conclusions. BL-M07D1 demonstrated encouraging efficacy in heavily pretreated HER2 expressing cancers, especially in HER2-positive BC. The safety profile showed ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06957886

A Study of BL-M07D1 Versus Investigator's Choice ... This trial is a registered, phase III, randomized, open-label and multicenter study to evaluate the efficacy and safety of BL-M07D1 in patients with ...

5. systimmune.com systimmune.com/documents/2025-ESMO-BL-M07D1-101-BC.pdf

BL-M07D1, a Novel HER2 Antibody-drug Conjugate, in ... BL-M07D1 demonstrated encouraging efficacy in patients with heavily pretreated breast cancers, especially in HER2- positive breast cancer. BL-M07D1 ...

6. prnewswire.com prnewswire.com/news-releases/systimmune-inc-to-present-new-clinical-data-on-izalontamab-brengitecan-and-bl-m07d1-highlighting-strength-of-differentiated-antibody-drug-conjugate-adc-platform-302564945.html

SystImmune, Inc. to Present New Clinical Data ... Safety and efficacy data of BL-M07D1 in patients with metastatic breast cancer and HER2-positive advance gastric or gastroesophageal ...