In a groundbreaking clinical trial, GSK has achieved remarkable patient survival results with its PD-1 inhibitor, Jemperli, when compared to Merck’s Keytruda, a market leader. New data, presented at the European Society for Medical Oncology (ESMO) 2023 Congress, revealed a 25% lower risk of death among patients with newly diagnosed nonsquamous non-small cell lung cancer (NSCLC) treated with Jemperli.
These findings stem from an updated analysis of the phase 2 PERLA trial, which marked the first-ever global head-to-head study of two PD-1 inhibitors. The enhanced overall survival data build on previous positive outcomes where Jemperli demonstrated a superior tumor response rate and time to tumor progression compared to Keytruda.
The latest update revealed that patients receiving Jemperli in combination with chemotherapy lived for a median of 19.4 months, while those in the Keytruda-chemo group survived for 15.9 months. Approximately half of the trial participants had succumbed to the disease by the time of the data cutoff.
Notably, Jemperli’s performance in PD-L1-negative patients, which was previously less impressive, now showcases an advantage in overall survival across PD-L1 subgroups. In the PD-L1-negative category, Jemperli recipients had a median survival of 20.8 months, compared to Keytruda’s 16.1 months. For PD-L1-positive patients, the numbers were 18 months for Jemperli and 15.9 months for Keytruda. However, Jemperli’s advantage appears less pronounced in individuals with tumor PD-L1 expression ranging from 1% to 49%.
GSK is proceeding with a phase 3 trial that combines Jemperli with the chemotherapy docetaxel, with or without the experimental TIM-3 inhibitor cobolimab, in NSCLC patients who have progressed following first-line treatment with a PD-1/L1 inhibitor and chemotherapy. This trial is expected to yield results in the second half of 2024.
Jemperli’s competitive performance in NSCLC is promising for GSK, especially considering Keytruda’s substantial global sales of $20.9 billion in 2022. In contrast, Jemperli, with limited indications for previously treated, mismatch repair-deficient (dMMR) solid tumors, generated only £21 million in sales last year.
While Jemperli excelled in the NSCLC head-to-head trial, it appeared to perform less effectively than Keytruda in separate trials related to preventing disease progression in primary advanced or first recurrent endometrial cancer with mismatch repair-proficient tumors. Variations in patient follow-up frequency and recruitment criteria may have contributed to the differing outcomes observed in Jemperli’s RUBY trial and Keytruda’s NRG-GY018 trial for endometrial cancer.
During the ESMO conference, additional analyses from the RUBY trial, focusing on patients with different mutations and assessing the time to second disease progression or death, were also shared. The FDA has already granted approval for Jemperli as a first-line treatment for dMMR endometrial cancer based on RUBY data. GSK is now awaiting further overall survival data next year to determine the potential expansion of its use to a broader patient population, as only about a third of RUBY trial participants had passed away at the time of the previous analysis. This could mark a significant development in Jemperli’s reach and impact in the field of cancer treatment.
KOL Views:
“Exciting numerical OS advantage of dostarlimab+CT over pembrolizumab+CT 19.4 v 15.9m. However, was pembro+CT underperforming comparing to KN189, especially in PD-L1>50% subgroup? “
– USA
“The ‘non-cross-trial-comparison’ comparison by Noemi Reguart, comparing PERLA to KN-189, mOs Longer in KN-189 but also PD-L1 high Caution needed when comparing pembro + dostar, with Ph2 PERLA design & subgroups”
– UK
“ Dostarlimab performed well in the PERLA trial versus pembrolizumab. I would not interpret this as dostarlimab is superior – but it is a very valid option. And I love the boldness and confidence needed for a head to head study against an established standard.”
– USA
