BB-1701 for Breast Cancer
Recruiting in Palo Alto (17 mi)
+30 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Eisai Inc.
Must not be taking: Eribulin, Corticosteroids
Disqualifiers: Brain metastases, Pneumonitis, Heart failure, others
No Placebo Group
Prior Safety Data
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.
12345Is 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.
678910What 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.
1011121314Eligibility 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.
+7 more
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.
+12 more
Trial 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
Participant Groups
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.
4Treatment groups
Experimental Treatment
Group I: Part 2, Dose ExpansionExperimental Treatment1 Intervention
HER2-positive or HER2-low, unresectable or metastatic BC.
Group II: Part 1, Dose Optimization, Cohort 3Experimental Treatment1 Intervention
HER2-positive or HER2-low, unresectable or metastatic BC.
Group III: Part 1, Dose Optimization, Cohort 2Experimental Treatment1 Intervention
HER2-positive or HER2-low, unresectable or metastatic BC.
Group IV: Part 1, Dose Optimization, Cohort 1Experimental Treatment1 Intervention
HER2-positive or HER2-low, unresectable or metastatic BC.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fort Wayne Medical Oncology & HematologyFort Wayne, IN
NHO Revive Research Institute LLCLincoln, NE
Astera Cancer CareEast Brunswick, NJ
New Mexico Oncology Hematology ConsultantsAlbuquerque, NM
More Trial Locations
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Who Is Running the Clinical Trial?
Eisai Inc.Lead Sponsor
Bliss Biopharmaceutical (Hangzhou) Co., LtdIndustry Sponsor
References
The ErbB receptors as targets for breast cancer therapy. [2019]Breast carcinomas express high levels of ErbB receptors and their ligands, and their overexpression has been associated with a more aggressive clinical behavior. For these reasons therapies directed at these receptors have the potential to be useful anti-cancer treatments. A series of monoclonal antibodies (MAbs)3 directed against the EGF (ErbB1) receptor and the closely related HER2/Neu (ErbB2) receptor are currently under evaluation. These MAbs have shown promising preclinical activity and "chimeric" and "humanized" MAbs have been produced in order to obviate the problem of host immune reactions. These antibodies are currently being tested in clinical trials either alone or in combination with chemotherapeutic agents. Clinical activity with one of these antibodies, trastuzumab, a humanized anti-ErbB2 MAb, has been documented in patients with breast cancer in a series of clinical trials and has recently been approved for the therapy of patients with metastatic ErbB2 overexpressing breast cancer. In addition to antibodies, compounds that inhibit receptor tyrosine kinases have shown significant preclinical activity and are currently being evaluated in the clinic.
The epidermal growth factor receptor as a target for therapy in breast carcinoma. [2022]The epidermal growth factor (EGF) receptor and its ligands have an important regulatory role in breast carcinoma. We have produced a series of monoclonal antibodies (MAbs) directed against the external portion of the EGF receptor. These MAbs prevent the binding of the ligands to the receptor, block ligand-induced activation of the receptor, and can inhibit the growth of breast cancer cells both in tissue culture and in human tumor xenografts in nude mice. We have also shown that anti-EGF receptor antibodies greatly enhance the antitumor effects of chemotherapeutic agents active in breast cancer. Phase I clinical trials with single doses of MAb conducted in patients with tumors over-expressing EGF receptors demonstrated favorable pharmacokinetics, good tumor imaging, and a lack of toxicity. A human:murine chimeric antibody has been produced with comparable affinity and antitumor activity that will enable us to administer repeated doses of MAb either alone or in combination with chemotherapy. Our pre-clinical data support the concept that the EGF receptor may be an optimal target for treatment with receptor blocking antibodies, either alone or in combination with chemotherapy.
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]Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)-positive metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy.
Molecular imaging of HER2-expressing malignant tumors in breast cancer patients using synthetic 111In- or 68Ga-labeled affibody molecules. [2014]The clinical utility of a human epidermal growth factor receptor 2 (HER2)-targeting Affibody molecule for detection and characterization of HER2-positive lesions was investigated in patients with recurrent metastatic breast cancer.
Treating the HER2 pathway in early and advanced breast cancer. [2014]ERBB2 gene amplification occurs in ∼20% of human breast cancers (BC) and is associated with an adverse clinical prognosis, indicating that it may be playing a critical role in disease pathogenesis. Therapeutic strategies targeting pathologic ERBB2 overexpression have revolutionized the diagnosis and treatment of BC. Indeed, humanized anti-ERBB2 antibodies, small molecule ERBB2 kinase inhibitors and ERBB2-targeting antibody-drug conjugates have proven safety and efficacy based upon evidence from randomized phase III clinical trials. Recent progress in targeting ERBB2 alteration will be reviewed, with focus on data that has informed changes in clinical practice for the treatment of BC.
Eribulin mesylate: a novel halichondrin B analogue for the treatment of metastatic breast cancer. [2022]The pharmacology, pharmacokinetics, clinical efficacy, safety, and administration of eribulin in patients with metastatic breast cancer are reviewed.
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]The aim of this study was to assess efficacy and safety of eribulin with trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer.
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]Eribulin is approved for advanced breast cancers refractory to anthracyclines and taxanes. Efficacy according to sensitivity to previous therapies has been poorly explored.
Eribulin monotherapy improved survivals in patients with ER-positive HER2-negative metastatic breast cancer in the real world: a single institutional review. [2022]Despite being routinely prescribed worldwide for several years, data regarding the safety, efficacy, and survival benefit of eribulin in clinical settings for the treatment of metastatic breast cancer (MBC) are limited. This retrospective observational study investigated the survival benefit of eribulin compared with conventional chemotherapy regimens in Japanese women with MBC. Women with estrogen receptor (ER)-positive human epidermal growth factor receptor 2 (HER2)-negative (ER+/HER2-) MBC, including unresectable locally advanced breast cancer, treated at a single institution were included in this study. The primary efficacy measure assessed overall survival (OS), and safety was evaluated as the number of grade 3 and 4 adverse events. Of the 293 patients analyzed, 66 received eribulin (eribulin arm) and 227 received conventional chemotherapeutic agents excluding eribulin (noneribulin arm). The median OS from MBC diagnosis in the eribulin arm was 72.1 months (95 % CI 13.3-168.3) compared with 43.3 months (95 % CI 9.1-202.0) in the noneribulin arm [hazard ratio (HR): 0.67, 95 % CI 0.47-0.96; P = 0.025]. No significant differences were noted in OS between eribulin used as a first-/second-line or third-/>third-line treatment for MBC. No patient discontinued eribulin therapy due to AEs. In the eribulin arm, grade 4 neutropenia and grade 3 febrile neutropenia were observed in 8 (12.1 %) and 4 (6.1 %) patients, respectively. Eribulin therapy has a survival benefit in Japanese women with ER+/HER2- MBC in routine clinical practice, with no unexpected grade 3/4 AEs. Interestingly, eribulin might be beneficial as any line therapy for ER+/HER2- MBC.
A novel ErbB2 epitope targeted by human antitumor immunoagents. [2015]Two novel human antitumor immunoconjugates, engineered by fusion of a single-chain antibody fragment against human ErbB2 receptor, termed Erbicin, with either a human RNase or the Fc region of a human IgG(1) , are selectively cytotoxic for ErbB2-positive cancer cells in vitro and in vivo. These Erbicin-derived immunoagents (EDIAs) do not show the most negative properties of Herceptin, the only humanized mAb against ErbB2 used in the therapy of breast carcinoma: cardiotoxicity and the inability to act on resistant tumors. These differences are probably attributable to the different ErbB2 epitopes recognized by EDIAs and Herceptin, respectively, as we have previously reported that they induce different signaling mechanisms that control tumor and cardiac cell viability. Thus, to accurately identify the novel epitope recognized by EDIAs, three independent and complementary methodologies were used. They gave coherent results, which are reported here: EDIAs bind to a different ErbB2 epitope than Herceptin and the other human/humanized antibodies against ErbB2 reported so far. The epitope has been successfully located in region 122-195 of extracellular domain I. These findings could lead to the identification of novel epitopes on ErbB2 that could be used as potential therapeutic targets to mitigate anti-ErbB2-associated cardiotoxicity and eventually overcome resistance.
[Preparation and biological activities of monoclonal antibody against p185erbB2]. [2018]To produce anti- p185erbB2 monoclonal antibody and investigate its biological activities on cancer cells that overexpress p185erbB2.
First-in-human molecular imaging of HER2 expression in breast cancer metastases using the 111In-ABY-025 affibody molecule. [2016]The expression status of human epidermal growth factor receptor type 2 (HER2) predicts the response of HER2-targeted therapy in breast cancer. ABY-025 is a small reengineered Affibody molecule targeting a unique epitope of the HER2 receptor, not occupied by current therapeutic agents. This study evaluated the distribution, safety, dosimetry, and efficacy of (111)In-ABY-025 for determining the HER2 status in metastatic breast cancer.
Immunoselective cell growth inhibition by antibody-adriamycin conjugates targeting c-erbB-2 product on human cancer cells. [2019]Monoclonal antibodies targeting c-erbB-2 protooncogene product p185 were conjugated with adriamycin via a pH-sensitive spacer. The resultant antibody-adriamycin conjugates showed immunoselective binding, internalization and cytotoxicity to p185-positive human breast cancer cell SKBr-3 and gastric cancer cell MKN-7, but not to normal human lymphocytes.
Generation of monoclonal antibody CIBCgp185 against C-erbB-2 oncoprotein and its clinical evaluation. [2021]The C-erbB-2 proto-oncogene encodes the production of a cell surface receptor protein, with tyrosine kinase activity. Over expression of this gene either due to gene amplification and/or increased transcription has been observed and has been correlated with poor prognosis in patients with Breast (10-33%) and ovarian (20-33%) cancers. The very low levels of expression of C-erbB-2 by normal tissues makes this receptor a potential target for diagnosis and therapy with Monoclonal antibodies raised against its extracellular domain. One such monoclonal antibody designated as CIBCgp185 of IgG2a isotype has been generated in our laboratory using BT474 breast carcinoma cell line as immunogen. This monoclonal antibody immunoprecipitated a 185 KD glycoprotein. The specificity of this antibody was confirmed by the formation of a single discrete band and positive reaction with BT474 antigen in Western blot and Dot blot respectively. Flowcytometric analysis performed using various cancer cell lines revealed that this Monoclonal antibody exhibited high binding affinity with BT474 and SKBR3 cells whichoverexpresses C-erbB-2. By immunoperoxidase test, this antibody stained specifically the tumor cell membrane in frozen tissue sections of breast and ovarian tumors indicating overexpression of the C-erbB-2 product. All these results well correlated with those obtained using a control antibody ICR12, an anti-C-erbB-2 antibody. These studies clearly indicate that Monoclonal antibody CIBCgp185 might prove useful to identify tumors with over expression of C-erbB-2 which are often associated with poor prognosis and early recurrence.