Merck’s Keytruda is well established as the standard treatment for newly diagnosed metastatic non-small cell lung cancer. For PD-1 latecomer GSK, that’s the benchmark its Jemperli must live up to—and the drug has managed to do just that.
In a phase 2 trial, GSK’s Jemperli, used in tandem with chemotherapy, shrank tumors as well as Keytruda’s chemo combo in patients with newly diagnosed metastatic nonsquamous non-small cell lung cancer (NSCLC), GSK said Wednesday. The Perla trial has therefore met its primary goal.
GSK didn’t share information on how Jemperli fared against Keytruda on more advanced endpoints measuring the time to tumor progression or death, or on patients’ life expectancy. But investigators plan to share more detailed results at an upcoming medical meeting, the British pharma said.
The phase 2 study won’t enable any drug applications, “but it will inform future development plans” for GSK’s anti-PD-1 agent, GSK’s outgoing R&D chief Hal Barron said during an investor call in July.
Jemperli’s Perla trial enrolled 243 patients and is so far the largest global head-to-head trial of PD-1 inhibitors to read out in this frontline nonsquamous NSCLC population, GSK said.
Keytruda made its name in the biopharma world back in 2018 after its chemo combo cut the risk of death by 51% versus chemo alone in the same indication in the Keynote-189 trial. Merck offered an updated look at that study last month, linking an estimated 19.4% five-year survival rate to the Keytruda-chemo regimen.
GSK has yet to unveil a late-stage development plan for Jemperli in frontline NSCLC. Challenging Keytruda in that indication would be extremely hard, so GSK may aim to position Jemperli in areas with less competitive pressure.
Last April, Jemperli became the seventh PD-1/L1 to enter the U.S. market after an approval in previously treated advanced or recurrent mismatch repair-deficient (dMMR) endometrial cancer. It later that year added any dMMR solid tumors—regardless of location—to its label.
The next big event for Jemperli is an expected topline readout from the phase 3 Ruby trial in newly diagnosed endometrial cancer later this year.
Separately, GSK on Wednesday said it’s moving the COSTAR Lung trial into phase 3 following a positive review from an independent data monitoring committee. The three-arm trial is testing the combinations of Jemperli and the chemotherapy docetaxel with or without GSK’s investigational TIM-3 inhibitor against docetaxel alone in NSCLC patients who have progressed on frontline treatment of a PD-1/L1 and chemo. Both Jemperli and cobolimab were originally discovered by AnaptysBio and licensed to Tesaro, which has become part of GSK.
These trials “support the ambition for [Jermperli] to become the backbone” of GSK’s R&D program, “particularly in patients with currently limited treatment options,” Hesham Abdullah, GSK’s head of oncology development, said in a Wednesday statement.
Head-to-head clinical trials of cancer drugs within the same class are rare. But for some PD-1/L1 contenders, a trial against Keytruda may be unavoidable in some cases.
Companies that self-develop a PD-1/L1 want to be free of Keytruda in their clinical trials because buying the Merck drug can significantly push up expenses and limit their R&D flexibility. But before the PD-1/L1 latecomers can explore novel combinations, they need to first establish their PD-1/L1 offering’s ability as a single agent—and there’s probably no way around testing versus Keytruda—at least in first-line NSCLC.
The FDA earlier this year rejected Eli Lilly and Innovent Biologics’ PD-1 drug Tyvyt, used in combo with chemo, in newly diagnosed advanced nonsquamous NSCLC partly because its phase 3 trial used chemo as the comparator, which the agency believes is an outdated control regimen.
Meanwhile, Regeneron’s FDA application for its PD-1 inhibitor Libtayo in front-line NSCLC has been delayed. The FDA had originally set a target decision date for Sept. 19.