Dostarlimab Plus Chemotherapy Shows Promise in Non-Small Cell Lung Cancer

Results from the largest head-to-head trial of programmed death receptor-1 inhibitors suggest that dostarlimab and chemotherapy could be an effective treatment option for patients with metastatic non-squamous non-small cell lung cancer.

Dostarlimab (Jemperli; GSK) showed positive headline results for first-line patients with metastatic non-squamous non-small cell lung cancer (NSCLC), according to a GSK press release. The drug was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

Dostarlimab met the trial’s primary endpoint of objective response rate for the combination treatment with chemotherapy. Key secondary endpoints were progression-free survival, overall survival (OS), and safety.

“These trials support the ambition for dostarlimab to become the backbone of our ongoing immuno-oncology-based research and development program(me) when used alone and in combination with standard of care and future novel cancer therapies, particularly in patients with currently limited treatment options,” said Hesham Abdullah, senior vice president, global head of Oncology Development, in the press release.

The trial’s goal was to evaluate the safety and efficacy of dostarlimab and chemotherapy in patients with metastatic non-squamous NSCLC. The researchers did not seek to determine superiority, but instead to compare the treatment combination against pembrolizumab plus chemotherapy.

PERLA was a double-blind, randomized 1:1 phase 2 trial that enrolled 243 patients with metastatic non-squamous NSCLC. It compared the programmed death receptor-1 (PD-1) inhibitors dostarlimab with pembrolizumab as combination treatments with chemotherapy. Eligible patients did not have known sensitizing epidermal growth factor receptor, anaplastic lymphoma kinase, or receptor tyrosine kinase-2 mutation, or other genomic mutations that already have therapy options.

Dostarlimab showed a safety and tolerability profile that matches the results of previous trials examining dostarlimab treatment combinations. The most common adverse events were anemia, asthenia, nausea, constipation, cough, dyspnoea, vomiting, decreased appetite, and neutropenia, according to the press release.

Dostarlimab binds to the PD-1 receptor and prevents it from interacting with PD-L1/2 ligands. As part of a combination therapy, dostarlimab is also being studied for patients with advanced endometrial cancer, stage 3 or 4 non-mucinous epithelial ovarian cancer, and in any patient who has metastatic cancer or a solid tumor.

Concurrently, GSK will progress with the 3-arm COSTAR Lung phase 3 trial. COSTAR is a randomized, open label trial that will compare cobolimab with dostarlimab, dostarlimab with docetaxel, and docetaxel monotherapy in 750 patients who have advanced NSCLC. Patients who are enrolled in the COSTAR phase 3 trial must have cancer progression after prior chemotherapy and anti-PD-L1 therapy, and the primary endpoint is OS.

Dostarlimab treatment is not approved anywhere as a first-line combination treatment with chemotherapy for patients with metastatic non-squamous NSCLC, nor is it approved to treat patients whose cancer has advanced following the combination therapy.

Reference

GSK. 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. GSK website. Octover 5, 2022. Accessed on October 5, 2022. https://www.gsk.com/en-gb/media/press-releases/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/