Dostarlimab and Chemotherapy Combo Meets Primary End Point of ORR in Advanced NSCLC

Preliminary results of the phase 2 PERLA trial (NCT04581824) highlighted that the primary end point of overall response rate (ORR) with dostarlimab-gxly (Jemperli) and chemotherapy was met in a population of patients with metastatic non-squamous non-small lung cancer (NSCLC), according to a press release from GSK.¹

Final data for the trial including the primary end point and the key secondary end point, progression-free survival (PFS) among PD-L1–expressing patients, will be detailed at an upcoming scientific conference.

The ongoing PERLA trial is an international, double-blind, randomized trial designed to compare the efficacy and safety of dostarlimab and chemotherapy with pembrolizumab (Keytruda) and chemotherapy in a population of 243 patients with advanced NSCLC. Trial participants assigned to the experimental arm received 500 mg of intravenous dostarlimab every 3 weeks for a maximum of 35 cycles lasting 21 days followed by chemotherapy consisting of 500 mg of intravenous dose of pemetrexed taken every 3 weeks for a maximum of 35 cycles, a 75 mg/m2 intravenous cisplatin infusion every 3 weeks for 4 cycles, and intravenous carboplatin up to 750 mg every 3 weeks for 4 cycles. In the active comparator arm, patients received a 200 mg dose of pembrolizumab via 30-minute infusion every 3 weeks up to a maximum of 35 cycles followed by the backbone chemotherapy.

Adult patients were eligible to participate in the PERLA trial if they had histologically confirmed metastatic non-squamous NSCLC with a documented absence of a sensitizing EGFR, ALK, ROS-1, or BRAF V600E mutations for which approved targeted therapies are available. Additional inclusion criteria included having measurable disease with at least 1 measurable lesion per RECIST v1.1 criteria, documented PD-L1 status by the 22C3 pharmDx assay, an ECOG performance status of 0 or 1, a life expectancy of at least 3 months, and adequate organ function.

Dostarlimab is also under investigation in combination with TIM-3 antagonist cobolimab as part of the phase 2/3 COSTAR Lung trial (NCT04655976). The global, randomized, open-label trial is assessing the efficacy and tolerability of cobolimab, dostarlimab, and docetaxel compared with dostarlimab and docetaxel and docetaxel monotherapy in patients with advanced NSCLC whose disease has progressed following prior anti–PD-1 therapy and chemotherapy. The primary end point of the trial is overall survival.

“[The PARLA and COSTAR] trials support the ambition for dostarlimab to become the backbone of our ongoing immuno-oncology-based research and development programme when used alone and in combination with standard of care and future novel cancer therapies, particularly in patients with currently limited treatment options,” Hesham Abdullah, senior vice president and global head of oncology development at GSK, said in the press release.

The safety profile of dostarlimab in the PERLA trial was comparable with previous clinical studies involving similar regimens. The most frequent treatment-emergent adverse effects (TEAEs) included anemia, asthenia, nausea, constipation, coughing, dyspnea, vomiting, decreased appetite, and neutropenia.

Dostarlimab received accelerated approved from the FDA for patients with mismatch repair–deficient solid tumors who progressed following prior therapy in August 2021.² Continued approval for the agent is dependent on further clinical benefit reported in a confirmatory trial.

References

1. GSK announces positive headline results from PERLA, the phase II trial of Jemperli (dostarlimab) plus chemotherapy in patients with metastatic non-squamous non-small cell lung cancer. News release. GlaxoSmithKline. October 5, 2022. Accessed October 6, 2022. https://bit.ly/3ecKyAS
2. GSK receives FDA accelerated approval for JEMPERLI (dostarlimab-gxly) for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumours. News release. GlaxoSmithKline. August 17, 2021. Accessed October 6, 2022. https://bit.ly/3iQxHnj