BB-1701 for Breast Cancer

Recruiting at 49 trial locations

Overseen By Eisai Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eisai Inc.

Must not be taking: Eribulin, Corticosteroids

Disqualifiers: Brain metastases, Pneumonitis, Heart failure, 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: Unknown

135 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of the Dose Optimization (Part 1) of this study is to assess the safety and tolerability of BB-1701 and to determine the recommended dose (RD) of BB-1701 for Dose Expansion (Part 2). The primary purpose of Dose Expansion (Part 2) is to assess the antitumor activity of BB-1701 at RD in the selected population(s) of breast cancer (BC).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have received any anticancer therapy or investigational drugs within the past 28 days before starting the study.

What data supports the effectiveness of the drug BB-1701 for breast cancer?

Research shows that targeting the HER2 receptor, which is overexpressed in some breast cancers, with humanized monoclonal antibodies like trastuzumab has been effective in improving outcomes for patients. BB-1701, which also targets HER2, may have similar potential based on this evidence. ^{1 2 3 4 5}

Is BB-1701 safe for humans?

Eribulin, a component of BB-1701, has been studied for safety in breast cancer patients. Some patients experienced serious side effects like low white blood cell counts and fever, but no unexpected severe side effects were reported. ^{6 7 8 9 10}

What makes the drug BB-1701 unique for treating breast cancer?

BB-1701 is unique because it combines a humanized monoclonal antibody targeting HER2 with eribulin, a chemotherapy agent, allowing it to specifically target and kill cancer cells that overexpress the HER2 protein, potentially reducing side effects compared to traditional chemotherapy. ^{10 11 12 13 14}

Eligibility Criteria

This trial is for individuals who have been previously treated for breast cancer that tests positive or low for HER2 and cannot be surgically removed or has spread. Specific eligibility details are not provided, but typically include health status and prior treatments.

Inclusion Criteria

Life expectancy of at least 3 months

My breast cancer is HR-positive, HER2-low, and endocrine therapy is no longer effective for me.

I've had 1-3 chemotherapy treatments for cancer that couldn't be surgically removed.

Exclusion Criteria

I need drainage for relief from fluid buildup due to cancer.

I have an active TB infection.

I am not allergic to monoclonal antibodies or corticosteroids.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Optimization

Participants receive BB-1701 to assess safety, tolerability, and determine the recommended dose

Up to 35 months

Dose Expansion

Participants receive BB-1701 at the recommended dose to assess antitumor activity

Up to 35 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• BB-1701

Trial Overview The study is testing BB-1701's safety, tolerability, and optimal dosing in part one. In part two, it will evaluate the effectiveness of BB-1701 at the recommended dose in selected breast cancer populations.

Participant Groups

Group I: Part 2, Dose Expansion Experimental Treatment 1 Intervention

HER2-positive or HER2-low, unresectable or metastatic BC.

Group II: Part 1, Dose Optimization, Cohort 3 Experimental Treatment 1 Intervention

HER2-positive or HER2-low, unresectable or metastatic BC.

Group III: Part 1, Dose Optimization, Cohort 2 Experimental Treatment 1 Intervention

HER2-positive or HER2-low, unresectable or metastatic BC.

Group IV: Part 1, Dose Optimization, Cohort 1 Experimental Treatment 1 Intervention

HER2-positive or HER2-low, unresectable or metastatic BC.

Who Is Running the Clinical Trial?

Eisai Inc.

Lead Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Bliss Biopharmaceutical (Hangzhou) Co., Ltd

Industry Sponsor

Trials

4

Recruited

930+

Findings from Research

Monoclonal antibodies targeting ErbB receptors, particularly trastuzumab for the HER2/Neu receptor, have shown significant clinical activity in treating metastatic breast cancer, leading to its approval for patients with ErbB2 overexpression.

These therapies, including both monoclonal antibodies and receptor tyrosine kinase inhibitors, are being tested in clinical trials, indicating a promising direction for targeted cancer treatments that may improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ErbB receptors as targets for breast cancer therapy. Albanell, J., Baselga, J.[2019]

Monoclonal antibodies targeting the epidermal growth factor (EGF) receptor effectively block ligand binding and receptor activation, inhibiting breast cancer cell growth in both lab cultures and human tumor models in mice.

Phase I clinical trials showed that these antibodies have favorable pharmacokinetics, good tumor imaging capabilities, and no toxicity, suggesting they are safe for use and can enhance the effects of chemotherapy in treating breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The epidermal growth factor receptor as a target for therapy in breast carcinoma. Baselga, J., Mendelsohn, J.[2022]

In a phase 3 study involving 500 women with ERBB2-positive metastatic breast cancer, a proposed trastuzumab biosimilar showed an overall response rate of 69.6%, which is comparable to 64.0% for the original trastuzumab, indicating that the biosimilar is equally effective in treating this condition.

Both the proposed biosimilar and trastuzumab had similar safety profiles, with high rates of adverse events, but no significant differences in serious side effects or overall survival, suggesting that the biosimilar could be a safe alternative to the original drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Randomized Clinical Trial. Rugo, HS., Barve, A., Waller, CF., et al.[2018]

The study involved three patients with recurrent metastatic breast cancer who received a HER2-targeting Affibody molecule labeled with either (111)In or (68)Ga, which was well tolerated and showed promising safety profiles.

The radiolabeled Affibody detected 9 out of 11 (18)F-FDG-positive metastases within 2-3 hours post-injection, suggesting its potential for rapid localization of HER2-positive lesions and providing valuable information that traditional imaging methods may not offer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic 111In- or 68Ga-labeled affibody molecules. Baum, RP., Prasad, V., Müller, D., et al.[2014]

ERBB2 gene amplification is found in about 20% of breast cancers and is linked to worse outcomes, highlighting its importance in the disease's development.

Targeting ERBB2 with therapies like humanized antibodies, kinase inhibitors, and antibody-drug conjugates has shown proven safety and effectiveness in phase III clinical trials, leading to significant advancements in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating the HER2 pathway in early and advanced breast cancer. Pegram, MD.[2014]

Eribulin mesylate is an effective treatment for metastatic breast cancer in patients who have already undergone at least two prior chemotherapy regimens, showing significant improvements in overall and progression-free survival in Phase III clinical trials.

This novel synthetic agent works by binding to the microtubule cap and inhibiting tubulin polymerization, leading to microtubule arrest, and has a manageable safety profile with low rates of peripheral neuropathy, primarily causing neutropenia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eribulin mesylate: a novel halichondrin B analogue for the treatment of metastatic breast cancer. McBride, A., Butler, SK.[2022]

In a phase II study involving 52 patients with locally recurrent or metastatic HER2+ breast cancer, the combination of eribulin and trastuzumab resulted in a high overall response rate (ORR) of 71.2%, indicating significant efficacy as a first-line treatment.

The treatment demonstrated a median progression-free survival (PFS) of 11.6 months and an acceptable safety profile, with the most common severe side effects being neutropenia and peripheral neuropathy, suggesting it is a viable option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2, multicenter, single-arm study of eribulin mesylate with trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer. Wilks, S., Puhalla, S., O'Shaughnessy, J., et al.[2022]

In a study of 250 patients with advanced breast cancer, eribulin treatment resulted in a median overall survival of 11.8 months and a median progression-free survival of 4.6 months, indicating its efficacy in this patient population.

The study found that patients who responded well to their last microtubule-inhibiting therapy had significantly longer overall survival when treated with eribulin, suggesting that previous treatment response can help predict the effectiveness of eribulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Results and Analysis of Eribulin Efficacy according to Previous Microtubules-Inhibitors Sensitivity in the French Prospective Expanded Access Program for Heavily Pre-treated Metastatic Breast Cancer. Sabatier, R., Diéras, V., Pivot, X., et al.[2022]

In a study of 293 Japanese women with metastatic breast cancer, those treated with eribulin had a median overall survival of 72.1 months, significantly longer than the 43.3 months for those receiving conventional chemotherapy, indicating a survival benefit for eribulin.

The safety profile of eribulin was acceptable, with no patients discontinuing treatment due to adverse events, and only a small percentage experiencing severe neutropenia, suggesting it is a tolerable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eribulin monotherapy improved survivals in patients with ER-positive HER2-negative metastatic breast cancer in the real world: a single institutional review. Watanabe, J.[2022]

The novel immunoconjugates, known as Erbicin-derived immunoagents (EDIAs), selectively target and kill ErbB2-positive cancer cells without causing the cardiotoxicity associated with Herceptin, making them a safer alternative for breast cancer treatment.

EDIAs bind to a different epitope on the ErbB2 receptor than Herceptin, which may explain their unique mechanism of action and potential to overcome resistance in tumors that do not respond to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel ErbB2 epitope targeted by human antitumor immunoagents. Troise, F., Monti, M., Merlino, A., et al.[2015]

The monoclonal antibody 1H3 was successfully produced and specifically binds to cancer cells that overexpress the p185erbB2 protein, as confirmed by various assays including ELISA and Western blot.

1H3 demonstrated the ability to significantly inhibit the proliferation of these p185erbB2-overexpressing cancer cells, indicating its potential as a targeted therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preparation and biological activities of monoclonal antibody against p185erbB2]. Han, M., Jiang, B., Wu, J., et al.[2018]

The study involving 7 patients with metastatic breast cancer demonstrated that (111)In-ABY-025 is safe and well tolerated, with no drug-related adverse events reported, making it a promising option for assessing HER2 status.

(111)In-ABY-025 imaging effectively differentiated between HER2-positive and HER2-negative metastases, providing high-contrast images within 4-24 hours, which could help guide treatment decisions in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human molecular imaging of HER2 expression in breast cancer metastases using the 111In-ABY-025 affibody molecule. Sörensen, J., Sandberg, D., Sandström, M., et al.[2016]

Monoclonal antibodies targeting the c-erbB-2 protein were successfully conjugated with adriamycin, demonstrating selective binding and internalization in cancer cells, specifically SKBr-3 breast cancer and MKN-7 gastric cancer cells.

The antibody-adriamycin conjugates exhibited cytotoxic effects on cancer cells while sparing normal human lymphocytes, indicating a targeted approach that may enhance treatment safety and efficacy in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoselective cell growth inhibition by antibody-adriamycin conjugates targeting c-erbB-2 product on human cancer cells. Suzuki, S., Tanaka, M., Masuko, T., et al.[2019]

The C-erbB-2 proto-oncogene is linked to poor outcomes in breast and ovarian cancers due to its overexpression, making it a promising target for diagnosis and therapy.

The monoclonal antibody CIBCgp185, developed in the lab, specifically binds to C-erbB-2 overexpressing cancer cells, indicating its potential use in identifying tumors associated with poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of monoclonal antibody CIBCgp185 against C-erbB-2 oncoprotein and its clinical evaluation. Meenakshi, A., Kumar, RS., Kumar, NS.[2021]

References

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

The ErbB receptors as targets for breast cancer therapy. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The epidermal growth factor receptor as a target for therapy in breast carcinoma. [2022]

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

Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Randomized Clinical Trial. [2018]

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

Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic 111In- or 68Ga-labeled affibody molecules. [2014]

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

Treating the HER2 pathway in early and advanced breast cancer. [2014]

6. England pubmed.ncbi.nlm.nih.gov

Eribulin mesylate: a novel halichondrin B analogue for the treatment of metastatic breast cancer. [2022]

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

Phase 2, multicenter, single-arm study of eribulin mesylate with trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer. [2022]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Results and Analysis of Eribulin Efficacy according to Previous Microtubules-Inhibitors Sensitivity in the French Prospective Expanded Access Program for Heavily Pre-treated Metastatic Breast Cancer. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Eribulin monotherapy improved survivals in patients with ER-positive HER2-negative metastatic breast cancer in the real world: a single institutional review. [2022]

10. England pubmed.ncbi.nlm.nih.gov

A novel ErbB2 epitope targeted by human antitumor immunoagents. [2015]

11. China pubmed.ncbi.nlm.nih.gov

[Preparation and biological activities of monoclonal antibody against p185erbB2]. [2018]

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

First-in-human molecular imaging of HER2 expression in breast cancer metastases using the 111In-ABY-025 affibody molecule. [2016]

13. Japan pubmed.ncbi.nlm.nih.gov

Immunoselective cell growth inhibition by antibody-adriamycin conjugates targeting c-erbB-2 product on human cancer cells. [2019]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Generation of monoclonal antibody CIBCgp185 against C-erbB-2 oncoprotein and its clinical evaluation. [2021]