ESMO26: BMS dual-acting ADC beats chemo in breast cancer

Bristol Myers Squibb and SystImmune's potentially first-in-class EGFRxHER3 bispecific antibody-drug conjugate has scored in another phase 3 trial, boosting its credentials as a future blockbuster.

In the PANKU-Breast01 study presented at ESMO, which enrolled patients with relapsed, HR-positive HER2-negative advanced breast cancer, izalontamab brengitecan (iza-bren) reduced the risk of disease progression or death by 59% compared to chemotherapy when used after at least one prior line of chemo.

Median progression-free survival (PFS) was 8.2 months, compared to 4.0 months with physicians' choice of chemo, and the confirmed objective response rate (cORR) for the two groups was 40.5% and 20.2%, respectively. Overall survival (OS) data remained immature at the interim analysis, and treatment discontinuations due to side effects were low in both treatment and control arms.

The new data comes a couple of years after BMS paid $800 million upfront for rights to the ADC (formerly known as BL-B01D1) from China-based SystImmune in a deal that could be worth as much as $8.4 billion if it meets regulatory and commercial targets.

At this year's ASCO, BMS and SystImmune also reported positive phase 3 results from the PANKU-Breast02 study in triple-negative breast cancer (TNBC) and PANKU-Esophagus01 in oesophageal squamous cell carcinoma. On Monday, delegates at ESMO will also see the first data from PANKU-Lung01 in EGFR-mutated non-small cell lung cancer (NSCLC).

Analysts have previously predicted peak annual sales for iza-bren could reach $3 billion to $5 billion or more, depending on the breadth of its label across different cancers, and BMS has said the ADC will be a cornerstone of its oncology business after it loses patent protection for $10 billion-a-year PD-1 inhibitor Opdivo (nivolumab) in around 2028.

It has been hypothesised that inhibiting EGFR and HER3 in tandem could improve efficacy and overcome resistance to currently available EGFR-directed drugs.

"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 Prof Binghe Xu of the Chinese Academy of Medical Sciences (CAMS).

"PANKU-Breast01 provides encouraging evidence for a new therapeutic approach," he added.

Earlier this year, China's National Medical Products Administration (NMPA) approved iza-bren for the treatment of recurrent or metastatic nasopharyngeal carcinoma and recurrent or metastatic oesophageal squamous cell carcinoma. The drug is distributed in China by SystImmune's parent company Sichuan Biokin Biopharmaceutical.