BB-1701 is an antibody-drug conjugate (ADC) consisting of a humanized IgG1K monoclonal antibody A with the same sequence as trastuzumab and eribulin linked together by a cathepsin-cleavable valine-citrulline linker. This innovative approach holds promise for treating a spectrum of solid tumors, notably HER2-expressing breast and lung cancers. 

Following the lead of AstraZeneca and Daiichi Sankyo in showcasing the efficacy of HER2-directed ADCs, Eisai clinched a significant deal with Bliss Biopharmaceutical in May 2023. This strategic collaboration positions Eisai as a frontrunner in the race to develop effective HER2-targeted therapies. With an upfront fee and the option for co-development of BB-1701, Eisai is strategically positioning itself to leverage the surging interest in HER2 ADCs. It is paving the way for Phase II trials in the US. Positive outcomes from these trials could position BB-1701 as a contender in the competitive landscape of HER2-positive or HER2-low unresectable or metastatic breast cancer treatments. The results presented at ASCO 2024 were as follows:

Efficacy outcomes 

Among the total of 40 patients, 38 patients were evaluable for preliminary antitumor activity, and 2 patients did not have the results of tumor assessment after treatment of BB-1701.

Safety result: 

• The most common treatment-emergent adverse events are peripheral neuropathy, leukopenia, neutropenia, anemia, and thrombocytopenia.

• The most commonly reported ≥ Grade 3 TEAEs are peripheral neuropathy, neutropenia, leukopenia, and thrombocytopenia

• There are no Grade 4 or Grade 5 adverse events 

• One patient discontinued the study treatment due to peripheral neuropathy. There are no interstitial lung diseases observed during the study

KOL insights

“BB-1701 has a manageable safety profile for breast cancer patients.” –Expert Opinion.

“BB-1701 comprises anti-HER2 antibody and eribulin and has a unique mechanism of action (MOA) including potent bystander effect and immunogenic cell death (ICD) activity.”–Expert Opinion.

Conclusion- 

With Enhertu leading the first place in HER2 low breast cancer space, other emerging players are entering this segment. Eisai’s BB-1701 is characterized by its payload of eribulin, which is a product of modern synthetic organic chemistry that has already made contributions to patients with breast cancer. Presented data in poster sessions included an overview of a Phase II study of BB-1701 in previously treated patients with HER2-low unresectable or metastatic breast cancer. It shows promising antitumor activity and a manageable safety profile in HER2 low-expressing breast cancer, including patients who received prior anti-HER2 ADCs.