GSK’s emerging oncology business just got a much-needed boost after several recent setbacks.
Last month, the Big Pharma said its PD-1 inhibitor Jemperli matched up to Merck & Co.’s Keytruda at shrinking non-small cell lung cancer (NSCLC) in a phase 2 trial. Now, GSK has more information to share. And the data look solid—at least so far.
Used in combination with chemotherapy, Jemperli cut the risk of disease progression or death by 30% over Keytruda and chemo in newly diagnosed metastatic nonsquamous NSCLC, although the study wasn’t designed to show superiority. On that key secondary endpoint, Jemperli and chemo stalled tumor progression or death for a median 8.8 months, compared with 6.7 months for the Keytruda-chemo regimen.
The data came from the PERLA trial, which enrolled 243 patients and was the first randomized global phase 2 study to directly compare two PD-1 inhibitors in this NSCLC setting, the investigators noted in an abstract
Before the presentation, an abstract showed that Jemperli shrank tumors in 46% of patients. That compared with 37% of patients in the Keytruda-chemo combo arm. With Jemperli matching Keytruda in reducing tumors, the PERLA trial met its primary endpoint.
The results demonstrated “really strong clinical activity for [Jemperli] when it’s benchmarked against what is one of the leading PD-1 inhibitors in first-line non-small cell lung cancer when it’s combined with chemotherapy,” Hesham Abdullah, GSK’s global head of oncology development, said in an interview with Fierce Pharma.
Data on Jemperli’s tumor response duration and its ability to extend patients’ lives require longer follow-up, Abdullah said. GSK expects to report more information on those markers in the second half of 2023, he added.
In the study, the distribution of patients with various tumor PD-L1 expression levels—as determined by the tumor proportion score—were almost identical between the two arms. Jemperli showed a numerically better overall response rate and progression-free survival across those PD-L1 subgroups except for PD-L1-negative patients. In that group, Jemperli and chemo triggered a slightly lower response of 28% compared to 33% for Keytruda and chemo, but Jemperli’s tumor progression data looked slightly better there.
While PERLA met its primary endpoint, the win was more symbolic than market-disrupting. For one, the trial won’t lead to any direct regulatory filing because its statistical design wouldn’t meet registrational standards, Abdullah said.
Abdullah wouldn’t comment on whether GSK plans to pursue an FDA approval for Jemperli and chemo in frontline NSCLC with a phase 3 trial against Keytruda. The Big Pharma has to be open to various options, whether it is first-line lung cancer or a different stage of disease within the same tumor type or a different tumor type, Abdullah said, adding “those are all options that we’re evaluating at this moment.”
The latest data should also be examined with caution because the trial is relatively small. Keytruda’s chemotherapy combo won an approval in newly diagnosed nonsquamous NSCLC thanks to the historic finding that the regimen cut the risk of death by 51% in the phase 3 KEYNOTE-189 trial. That study included 616 patients and linked the Keytruda-chemo regimen to a 48% response rate, higher than what Jemperli and Keytruda delivered in their respective chemo cocktails in PERLA.
Nevertheless, Abdullah said the PERLA trial serves as a “proof-of-concept study,” which provides GSK a better understanding of Jemperli’s clinical activity against the current market leader. GSK is evaluating Jemperli both as a monotherapy and in combination with existing and novel therapies, including GSK’s own experimental drugs targeting the CD226 axis.
The PERLA trial gives GSK—and Jemperli as the seventh PD-1/L1 inhibitor on the U.S. market—a needed win on the oncology scoreboard.
This result comes after multiple setbacks for GSK’s cancer department. Zejula, currently the company’s bread-and-butter offering in oncology, had to withdraw a late-line ovarian cancer approval. It also limited a second-line maintenance use to exclude patients without BRCA mutations after the FDA raised patient survival concerns based on longer-term clinical trial data.
And just last week, GSK surprisingly pulled an accelerated approval for its BCMA-targeted multiple myeloma drug Blenrep at the request of the FDA. The move came just 15 days after the antibody-drug conjugate failed as a monotherapy against a cocktail of Bristol Myers Squibb’s Pomalyst and dexamethasone in myeloma patients who had tried two prior lines of therapy.
Editor's Note: The story was originally published at 18:05 ET on Nov. 30. The current version includes information on progression-free survival and additional comments from GSK's Hesham Abdullah.