GSK's Jemperli scores FDA nod for mismatch repair-deficient solid tumours

GlaxoSmithKline said the FDA has expanded the label for Jemperli (dostarlimab-gxly) to include treatment of adults with mismatch repair-deficient (dMMR) recurrent or advanced solid tumours. This is the second FDA approval for the PD-1 blocking antibody this year after it was cleared in April to treat recurrent or advanced dMMR endometrial cancer in patients who have progressed on or following platinum-containing chemotherapy (see ViewPoints: GlaxoSmithKline brings too little too late to the checkpoint marketplace).

The latest accelerated approval is based on objective response rate (ORR) and durability of response (DoR) results seen in the ongoing Phase I/II multi-cohort GARNET study testing Jemperli as monotherapy. The company said the data were drawn from cohort A1 involving dMMR endometrial cancer patients and cohort F of dMMR non-endometrial cancer patients with solid tumours, with colorectal, small intestine and stomach cancers being the most common in this group.

GARNET has an estimated enrolment of 740 patients with advanced solid tumours who have limited treatment options. Subjects received Jemperli 500mg via intravenous infusion once every three weeks for four doses, followed by Jemperli 1g once every six weeks until disease progression or unacceptable toxicity.

ORR of 41.6% across dMMR solid tumours

Among 209 patients with dMMR solid tumours, including endometrial and non-endometrial solid tumours, Jemperli was associated with an ORR of 41.6%, with complete responses accounting for 9.1%, while the rest were partial responses. GlaxoSmithKline said median DoR was 34.7 months, and that 95.4% of patients maintained a response of at least six months. In the dMMR solid tumor non-endometrial cancer cohort, which included 106 patients, results demonstrated an ORR of 38.7%. The most common Grade 3 or 4 adverse reactions were anaemia, fatigue/asthenia, increased transaminases, sepsis and acute kidney injury.

Meanwhile, GlaxoSmithKline also noted that the US prescribing information for Jemperli's endometrial cancer indication has been updated with data from an additional 32 patients in the A1 cohort. The new results show an ORR of 44.7%, which is up from 42.3% previously, with a DoR range from 2.6 to 35.8+ months. The drug was also approved earlier this year to treat recurrent or advanced endometrial cancer in the EU.

The company recently disclosed that the Phase II MOONSTONE study evaluating Jemperli plus its PARP inhibitor Zejula (niraparib) in patients with platinum-resistant ovarian cancer without a known BRCA mutation was stopped after an analysis suggested it would not meet the "high bar" set for the trial.