Bispecific Antibody Promising in EGFR Expressing NSCLC
BL-B01D1, an investigational EGFR and HER3 bispecific antibody-drug conjugate, being evaluated in patients with solid tumors, including those with EGFR-mutated and wild-type non–small cell lung cancer (NSCLC) and nasopharyngeal carcinoma. According to findings from a phase 1 study (NCT05194982) presented at the 2023 ASCO Annual Meeting BL-B01D1has significant anti-cancer activity in EGFR mutated NSCLC.
About EGFR NSCLC
The EGFR—which stands for “epidermal growth factor receptor”—contributes to the growth of some lung cancers and drugs that block the activity of EGFR slow cancer growth and prolong survival.
EGFRs are small proteins that are found on the surface of all cells. EGFR binds proteins circulating in the blood called growth factors. The binding action between EGFR and growth factors stimulates biological processes within the cell to promote growth of a cell in a strictly controlled manner. However, in many cancer cells, EGFR is either abundantly over-expressed or the EGFR biological processes that normally stimulate cell growth are constantly active. This leads to the uncontrolled and excessive growth of the cancer cell.
Guidelines from the International Association for the Study of Lung Cancer (IASLC) have been developed and they recommend testing for EGFR and ALK mutations, and PDL-1 in all individuals with newly diagnosed lung cancer.
Among people with NSCLC, EGFR mutations are most common in people of Asian ethnicity, women, never-smokers, and those with a type of lung cancer known as adenocarcinoma. EGFR mutations occur in 30–40% of NSCLC's in Asian populations compared to 10–15% in Western populations.
EGFR-targeted drugs that have been shown to benefit select patients with NSCLC belong to a class of drugs known as tyrosine kinase inhibitors (TKIs). The drugs enter the cell and interfere with EGFR from within.
Tagrisso (osimertinib) is currently the standard of care for patients with EGFR-mutated NSCLC, but the need for novel agents is underscored as disease progression on Tagrisso is inevitable. Bispecific antibodies, antibody-drug conjugates (ADCs), EGF vaccines, and fourth-generation EGFR TKIs are all under development to enrich the treatment paradigm.
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About BL-B01D1
BL-B01D1 is “bispecific antibody” and belongs to a novel class of cancer medicines currently undergoing development. Bispecific antibodies represent an innovative immunotherapy approach that helps the body’s immune system target cancer cells. Bispecific antibodies have two arms. One arm of the drug attaches to a specific protein on a cell. The other arm activates immune cells in the patient to kill the cancer cells.
The initial clinical trial evaluating BL-B01D1 was designed to determine the optimal dose and enrolled 195 patients, some with locally advanced or metastatic NSCLC and other solid tumors who had progressed on standard therapy or did not have other treatment options.
Overall, 63% of patients with EGFR-mutant NSCLC responded to treatment with BL-B01D1. All patients with EGFR-mutant NSCLC had experienced a recurrence following treatment with an EGFR TKI, 89% had received a previous third-generation EGFR TKI, and 74% had prior platinum-based chemotherapy. The researchers reported no association of response to BL-B01D1 and known resistance mechanism of EGFR TKIs.
“BL-B01D1 demonstrated promising anti-tumor activity in this heavily treated population, and tumor shrinkage was observed in nearly 80% of patients,” lead study author Li Zhang, MD, of State Key Laboratory of Oncology in South China, University Cancer Center in Guangzhou, China, said in a presentation of the data. “BL-B01D1 has promising anti-tumor activity in multiple tumor types, especially in EGFR-mutant and wild-type NSCLC, and nasopharyngeal carcinoma.”
The most common side effects from treatment included anemia, neutropenia, and thrombocytopenia, and no interstitial lung disease was observed
Reference
Zhang, L, Ma Y, Zhao Y, et al. BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic solid tumor: Results from a first-in-human phase 1 study. J Clin Oncol. 2023;41(suppl 16):3001. doi:10.1200/JCO.2023.41.16_suppl.3001
