GSK has reported the first global data for risvutatug rezetecan, known as Ris-Rez, its investigational B7-H3 targeted antibody drug conjugate licensed from China’s Hansoh Pharma, in patients with relapsed extensive stage small cell lung cancer. In the Phase 1b dose optimisation portion of the EMBOLD PanTumour-101 trial, the confirmed objective response rate was 61 percent among evaluable patients at the 8 mg/kg dose (11 of 18; 95 percent confidence interval 35.7 to 82.7), compared with 32 percent at 6 mg/kg (7 of 22; 13.9 to 54.9).
The dose separation is the point of the readout. Together with the statistically significant overall survival benefit Hansoh reported last month in its pivotal Chinese Phase 3 trial, the global data supported GSK’s selection of the 8 mg/kg dose for the global Phase 3 EMBOLD SCLC-301 study already under way. GSK holds exclusive worldwide rights outside mainland China, Hong Kong, Macau and Taiwan, and more than 1,000 patients have now received the drug across the EMBOLD program, which also includes a Phase 3 study in metastatic castration resistant prostate cancer.
Safety is the counterweight. At a median follow up of 100.5 days, grade 3 or higher treatment related adverse events occurred in 42 percent of patients on the higher dose against 15 percent on the lower dose, most commonly haematological. Interstitial lung disease, the class toxicity that shadows antibody drug conjugates, occurred in one of 50 patients (2 percent) and was grade 2.
The numbers are early and small. Eighteen evaluable patients at the selected dose, a confidence interval spanning 36 to 83 percent, and 100 days of follow up cannot establish durability in a disease where responses often fade quickly. What the readout does is remove the dose question and keep the program’s central claim, that a B7-H3 conjugate can work outside the Chinese trial population, intact heading into ESMO, where the data get a poster presentation in Madrid this week.