Bristol Myers Squibb (BMS) and SystImmune have reported positive Phase 3 results for izalontamab brengitecan (iza-bren), an investigational breast cancer drug that reduced the risk of disease progression or death by 59%.

 

This reduction is compared with chemotherapy in patients with advanced hormone receptor-positive (HR+)/HER2-negative breast cancer.

 

The findings from the randomised PANKU-Breast01 study showed that patients receiving iza-bren achieved a median progression-free survival (PFS) of 8.2 months, more than double the four months recorded among patients treated with chemotherapy.

 

The trial enrolled patients with unresectable locally advanced, recurrent or metastatic HR+/HER2-negative breast cancer whose disease had progressed after at least one prior line of chemotherapy.

 

An assessment by a blinded independent review committee found that iza-bren significantly improved the study’s primary endpoint, with a hazard ratio of 0.41. Overall survival data remained immature at the time of the interim analysis.

 

The confirmed objective response rate was 40.5% among patients receiving iza-bren, compared with 20.2% for chemotherapy. Median duration of response also increased to 6.9 months, against 4.2 months with chemotherapy.

 

The findings could offer a new treatment avenue for patients with advanced HR-positive, HER2-negative breast cancer, for whom therapeutic choices often narrow as the disease progresses.

 

“While there have been advances in the treatment landscape for HR-positive, HER2-negative advanced breast cancer, options can become increasingly limited as patients progress through available therapies, with most ultimately relying on chemotherapy,” said Professor Binghe Xu, Academician of the Chinese Academy of Engineering, Cancer Hospital Chinese Academy of Medical Sciences. 

 

“PANKU-Breast01 provides encouraging evidence for a new therapeutic approach. Unlike other ADCs, izalontamab brengitecan is designed to target both EGFR and HER3, and the reduction in the risk of disease progression or death suggests it could offer patients a meaningful new treatment option.”

 

Iza-bren is a potentially first-in-class bispecific antibody-drug conjugate (ADC) designed to target both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3). The dual-targeting approach is intended to deliver a cancer-killing payload to tumour cells while also blocking signals involved in cancer cell growth and survival.

 

The study reported a manageable safety profile, with no new safety signals identified.

 

Grade 3 or higher treatment-related adverse events were predominantly haematological. Researchers reported that these events could be managed with supportive care, while just 1.6% of patients discontinued iza-bren because of treatment-related adverse events.

 

Adjudicated interstitial lung disease was reported in two patients, or 1.1% of those receiving iza-bren, with both cases classified as Grade 1 or 2.

 

“The 59% reduction in progression or death we see with iza-bren represents a substantial advance for patients who have limited treatment options after prior chemotherapy,” said Jonathan Cheng, Chief Medical Officer of SystImmune. 

 

“This Phase 3 data, combined with our positive results in triple-negative breast cancer, demonstrates that our dual EGFRxHER3-targeting approach can meaningfully address the biology of multiple breast cancer subtypes and represents an important step towards more effective, precision-based treatment strategies.”

 

BMS said the PANKU-Breast01 results add to a growing body of clinical evidence supporting iza-bren’s potential across multiple cancers.

 

“The positive PANKU-Breast01 results are an important validation of iza-bren’s potential as an innovative scientific approach to overcome disease resistance and the limitations of currently available treatment options,” said Cristian Massacesi, executive vice president, chief medical officer and head of development, Bristol Myers Squibb. 

 

“Together with the clinical benefit iza-bren has shown in other tumor types, these data position iza-bren as a potentially first-in-class dual-targeting ADC therapy with the potential to become a new standard of care across the cancer treatment paradigm.”