Astellas Pharma’s zolbetuximab has gone two for two, chalking up a second phase 3 win to cement its status as the front-runner in the race to deliver a drug against one of the hottest targets in cancer today.
In November, the Japanese drugmaker reported that the SPOTLIGHT phase 3 clinical trial had linked the anti-CLDN18.2 antibody to improved progression-free survival (PFS) in a genetically defined population of gastric and gastroesophageal junction cancer patients. The success put Astellas one study away from having the data to file for approval of zolbetuximab.
Now, Astellas has reported data from its second placebo-controlled study, GLOW. As happened in the earlier trial, GLOW found adding the investigational antibody to a chemotherapy regimen improved PFS, the primary endpoint, and overall survival (OS) in CLDN18.2-positive, HER2-negative cancer patients.
The two studies targeted the same populations and enrolled similar numbers of patients, 507 in GLOW versus 566 in SPOTLIGHT. The key difference was the choice of chemotherapy regimen. GLOW used the capecitabine-oxaliplatin combination CAPOX while SPOTLIGHT used the mFOLFOX6 cocktail of oxaliplatin, leucovorin and fluorouracil.
Both trials randomized patients to take zolbetuximab or placebo on top of the chemotherapy regimens. In GLOW, the median PFS and OS durations achieved by the zolbetuximab-chemotherapy combination were lower than in SPOTLIGHT. But with the placebo arm also performing better in SPOTLIGHT, the deltas between the treatment and control groups were similar.
Median PFS in GLOW’s zolbetuximab group was 8.21 months, versus 6.8 months in the placebo cohort. The median PFS for zolbetuximab and the control in SPOTLIGHT were 10.61 months and 8.67 months, respectively. Similarly, the median OS for zolbetuximab and placebo in GLOW, 14.39 months and 12.16 months, were lower than the figures in SPOTLIGHT, 18.23 months and 15.54 months.
The safety and tolerability results from GLOW were consistent with previous studies, with the rates of nausea, vomiting and decreased appetite being the key differences between the treatment and control arms, and as such Astellas thinks it has the basis for regulatory submissions. Approval would enable Astellas to start recouping the 422 million euros ($452 million) it spent to acquire zolbetuximab in its 2016 takeover of Ganymed Pharmaceuticals, although it is also on the hook for more milestone payments.
Barring any regulatory snags, Astellas will become the first company to bring an anti-CLDN18.2 drug to market. It is unlikely to be the last. A long list of drug developers are tackling the target using a range of modalities, with AstraZeneca alone inking two deals in the past year for an antibody-drug conjugate and a bispecific antibody against CLDN18.2.