Novartis, BeiGene lay out frontline PhIII data for PD-1 drug as second-line PDUFA date looms
As the FDA prepares to decide on Novartis and BeiGene’s PD-1 drug tislelizumab in the second-line setting, the pair is already preparing for its potential use as patients’ first treatment option.
The two companies announced at an ESMO congress on gastrointestinal cancer Thursday that first-line patients on the anti-PD-1 antibody plus chemotherapy reported a median overall survival of 17.2 months versus 10.6 months for patients on chemo plus placebo. This meets the study’s primary endpoint of overall survival. The risk of death in patients on the PD-1 drug was also 34% lower than patients on placebo, clocking in a p-value of under 0.0001.
The Phase III study was investigating tislelizumab as a frontline therapy for adult patients with unresectable, locally advanced or metastatic esophageal squamous cell carcinoma (ESCC), regardless of a patient’s PD-L1 status. These data were reported less than two weeks before tislelizumab’s PDUFA date as a second-line treatment, which the FDA has set for July 12.
In patients with a PD-L1 score equal or above 10% (going for one of the secondary endpoints in the study), tislelizumab plus chemotherapy showed a median overall survival of 16.6 months, giving a 66% advantage over patients in the chemo plus placebo cohort, which saw a median OS of 10.0 months. Risk of death in the first group was reduced by 38%, with a p-value of p=0.002.
On the flip slide, in patients with PD-L1 score less than 10% as part of an exploratory analysis, the median OS for tislelizumab and chemotherapy was slightly higher than in the 10%-plus PD-L1 patient group, reporting 16.7 months versus 10.4 months in the control group.
Tislelizumab plus chemotherapy also significantly improved progression-free survival and objective response rate, each with p-values below 0.0001.
On safety, Novartis said that treatment-related adverse events were similar across both arms. Those events included anemia (68% in the tislelizumab group vs 61% in chemo only), decreased neutrophils (78% vs 80%), decreased white blood cell count (55% vs 65%), decreased appetite (39% vs 38%), nausea (37% vs 42%) and peripheral sensory neuropathy (26% vs 21%).
The drug candidate was also accepted for review by the EMA back in April, including in indications for multiple non-small cell lung cancer on top of ESCC.
Novartis paid BeiGene $650 million in cash upfront early last year to in-license tislelizumab and take it abroad, as BeiGene’s PD-1 inhibitor had already been approved in China for eight oncology indications so far. At the time the deal was inked, $1.55 billion in future regulatory/sales milestones and royalty rights were on the table.
So far, those markets include Japan, Europe and North America, comprising more than 30 countries so far. And with the FDA’s demonstrated reluctance earlier this year on granting drug approvals based solely on Chinese data, BeiGene and Novartis’ data contrast with a similar drug from Eli Lilly, as the pair conducted research at more than 160 trial sites, including in China, the US, Australia, Italy and Spain.