1296P - A phase II study to evaluate the efficacy and safety of BB-1701 in advanced or metastatic NSCLC patients with HER2 mutation/amplification

Background

BB-1701 is an antibody-drug conjugate (ADC) consisting of a humanized anti-HER2 antibody and eribulin. After BB-1701 is internalized in HER2 expressing cancer cells, free eribulin is cleaved from the ADC by cathepsin b and causes cytotoxicity to cancer cells. The neighboring cells are affected with bystander effects, like cytotoxicity on tumor cells and non-cytotoxic effects on microenvironment by free eribulin. We report the preliminary efficacy and safety results from the ongoing phase 2 study of BB-1701 in advanced or metastatic NSCLC patients with HER2 mutation/amplification.

Methods

Patients enrolled were ≥ 18 years of age, had confirmed locally advanced/metastatic HER2 mutant/amplified NSCLC, an ECOG PS <2; measurable lesion(s) (per RECIST v1.1); and had previously been treated with ≥1 line(s) of prior antitumor therapy. HER2 expression was determined by NGS or PCR before enrollment. The dose level of BB-1701 is 1.6 mg/kg Q3W.

Results

As of 22 April 2024, 26 patients were enrolled and treated. Median age was 57 years, 38.5 %/61.5 % patients were female/male, and 11.5 %/88.5 % patients had ECOG PS 0/1. The mean number of prior systemic therapy lines was 2.3, 88.5%/11.5% HER2 status were mutation/amplification. All 26 patients experienced at least one treatment-related adverse events (TRAEs). The most common (≥ 20%) all grade TRAEs were peripheral neuropathy, alopecia, hypercholesterolemia, AST increased, ALT increased, lipase increased, hypertriglyceridemia, and platelet count decreased. The grade 3 TRAE were anemia and hepatic function abnormal. There were no grade 4 and 5 TRAE. The treatment related serious adverse events experienced by 3 patients were pneumonia, anemia and hepatic function abnormal. There was no interstitial lung disease reported as of now. Efficacy were evaluated in 24 patients as of 30 Apr: 12 patients achieved partial response and 10 patients had stable disease, with best overall response of 50.0% and disease control rate of 91.7%. More data will be presented at the ESMO meeting.

Conclusions

BB-1701 has demonstrated promising antitumor activity and a manageable safety profile in patients with HER2 mutant/amplified NSCLC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Bliss Biopharmaceutical (Hangzhou) Co., Ltd.

Funding

Bliss Biopharmaceutical (Hangzhou) Co., Ltd.

Disclosure

C. Zhou: Financial Interests, Personal, Advisory role, Consulting fees: Innovent Biologics, Qilu, Hengrui, TopAlliance Biosciences Inc.; Financial Interests, Personal, Other, Payment or honoraria from: Eli Lilly China, Sanofi, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Qilu, Hengrui, Innovent Biologics, Alice, C-Stone, LUYE Pharma, TopAlliance Biosciences Inc., Amoy Diagnostics, AnHeart. H. Tang, X. Tian, Y. Zhou, Z. Wei: Financial Interests, Personal, Full or part-time Employment: Bliss Biopharmaceutical (Hangzhou) Co., Ltd. All other authors have declared no conflicts of interest.