Dostarlimab Plus Chemotherapy Meets ORR End Point in Metastatic Nonsquamous NSCLC

Hesham Abdullah

The addition of dostarlimab-gxly (Jemperli) to chemotherapy led to an improvement in objective response rate (ORR) vs pembrolizumab (Keytruda) plus chemotherapy in patients with newly diagnosed metastatic nonsquamous non–small cell lung cancer (NSCLC), according to topline findings from the phase 2 PERLA trial (NCT04581824).¹

Full results from the study will be presented at an upcoming medical meeting.

“These trials support the ambition for dostarlimab to become the backbone of our ongoing immuno-oncology-based research and development program 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, Global Head of Oncology Development, GSK, said in a press release.

PERLA is a global, randomized, double-blind phase 2 trial of 243 patients evaluating the efficacy and safety of dostarlimab plus chemotherapy vs pembrolizumab plus chemotherapy in patients with metastatic nonsquamous NSCLC without a known sensitizing EGFR, ALK, ROS1, or BRAF V600E mutation or other genomic mutation for which an approved targeted therapy is available.²

Eligible patients will be randomly assigned to receive 500 mg of intravenous (IV) dostarlimab on day 1 of every 21-day cycle followed by 500 mg/m² of pemetrexed (Alimta) and 75 mg/m² of cisplatin or carboplatin at an area under the curve of 5 mg/mL/min for a maximum dose of 750 mg in cycles 1 to 4 per investigator decision, or 200 mg of IV pembrolizumab followed by chemotherapy in the same schedule. The checkpoint inhibitors will be given up to a maximum of 35 cycles.

The primary end point is ORR assessed by blinded independent central review per RECIST v1.1 criteria. Secondary end points include investigator-assessed progression-free survival per RECIST v1.1 criteria, overall survival (OS), and safety.

Notably, topline findings showed that safety and tolerability of dostarlimab was similar to that seen in prior clinical trials with the agent. The most frequent treatment-emergent adverse effects were anemia, asthenia, nausea, constipation, cough, dyspnea, vomiting, decreased appetite, and neutropenia.

In addition, both arms of the phase 2/3 COSTAR Lung trial (NCT04655976) will move forward into phase 3.³ The decision follows the recommendation from the Independent Data Monitoring Committee, given that the trial met its prespecified expansion criteria per protocol.

COSTAR Lung is a randomized, open label, 3-arm phase 2/3 trial comparing cobolimab, an investigational selective anti–TIM-3 monoclonal antibody, plus dostarlimab plus docetaxel with dostarlimab plus docetaxel and docetaxel alone in 750 patients with advanced nonsquamous NSCLC who have progressed on prior anti–PD-L1 therapy and platinum doublet–based chemotherapy.

The study does not include patients with a known sensitizing EGFR, ALK, or ROS1 mutation, for which an approved targeted therapy is available. The primary end point is OS.

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. GSK. October 5, 2022. Accessed October 5, 2022. https://bit.ly/3CBV12e
2. Efficacy comparison of dostarlimab plus chemotherapy versus pembrolizumab plus chemotherapy in participants with metastatic non-squamous non-small cell lung cancer (NSCLC). ClinicalTrials.gov. Updated June 28, 2022. Accessed October 5, 2022. https://clinicaltrials.gov/ct2/show/NCT04581824
3. Efficacy comparison of cobolimab + dostarlimab + docetaxel to dostarlimab + docetaxel to docetaxel alone in participants with advanced non-small cell lung cancer who have progressed on prior anti-programmed death-ligand 1 (PD-[L]1) therapy and chemotherapy (COSTAR Lung). ClinicalTrials.gov. Updated April 19, 2022. Accessed October 5, 2022. https://clinicaltrials.gov/ct2/show/NCT04655976