Dostarlimab Extends PFS and Elicits Better Responses vs Pembrolizumab in NSCLC

Frontline treatment with dostarlimab and chemotherapy reduced the risk of disease progression and led to better objective response rates and progression-free survival vs pembrolizumab in patients with metastatic non-squamous non–small cell lung cancer.

Dostarlimab (Jemperli) plus chemotherapy achieved a positive confirmed objective response rate (ORR) and median progression-free survival (mPFS) vs pembrolizumab (Keytruda) and chemotherapy as a first-line treatment for patients with metastatic non-squamous non–small cell lung cancer (NSCLC), according to findings from the phase 2 PERLA trial (NCT04581824).1

Patients treated with the dostarlimab combination elicited a confirmed ORR of 46% vs 37% with the pembrolizumab combination. For the key secondary end point of mPFS, rates were 8.8 months with dostarlimab and 6.7 with pembrolizumab.

“Understanding the role of immuno-oncology treatments in the NSCLC patient population is a significant goal we’re committed to in the oncology community. Despite advancements in treatment options, unmet need persists for health care providers and their patients. The data results presented at [the European Society for Medical Oncology [ESMO] Immuno-Oncology Congress 2022] add to the body of evidence of immuno-oncology agents such as dostarlimab and enhance our knowledge in this important area of research,” said Solange Peters, MD, PhD, professor and chair of medical oncology at the University Hospital of Lausanne, Switzerland, and ESMO president, in the press release.

The randomized, double-blind, phase 2 PERLA trial enrolled 243 patients, making it the largest global head-to-head trial of PD-1 inhibitors in this patient population. Investigators evaluated the efficacy and safety of the combination of dostarlimab and chemotherapy vs pembrolizumab plus chemotherapy in patients with metastatic non-squamous NSCLC.2

Those enrolled did not have a known sensitizing EGFR, ALK, ROS-1, or BRAF V600E mutation or other genomic aberration for which an approved targeted therapy is available. Patients must have had measurable disease presenting with at least 1 measurable lesion RECIST v1.1 as determined by the local site Investigator/radiology assessment, documented PD-L1 status, an ECOG performance status score of 0 or 1, a life expectancy of at least 3 months, adequate organ function, and had recovered to grade 1 or less from any prior treatment-related toxicities at the time of randomization.

The primary end point of the trial was ORR with secondary end points including investigator-assessed PFS, overall survival, and safety.

In the experimental arm, patients were given dostarlimab at 500 mg on day 1 of every 21-day cycle followed by pemetrexed, and cisplatin or carboplatin on cycles 1 to 4 only. Patients in the active comparator arm were administered pembrolizumab on day 1 of every 21-day cycle followed by pemetrexed, and then followed by cisplatin or carboplatin on cycles 1 to 4 as well.

Findings revealed that the primary endpoint of ORR was 46% in 56 of 121 patients treated with dostarlimab vs 37% in 45 of 122 patients given pembrolizumab, creating a difference of 9.32% (80% CI, 1.46%-17.18%).

For the key secondary end point, mPFS was 8.8 months (95% CI, 6.7-10.4) in the dostarlimab treatment arm compared with 6.7 months (95% CI, 4.9-7.1) in the pembrolizumab treatment arm (HR 0.70; 95% CI, 0.50-0.98).

Patients with a PD-L1 tumor proportion score (TPS) of <1% had an ORR of 28% with dostarlimab and chemotherapy (n = 50) and 33% for pembrolizumab plus chemotherapy (n = 51). The PFS rates were 7.0 months and 6.9 months, respectively (HR, 0.77; 95% CI, 0.46-1.28). For those with a PD-L1 TPS of 1% or greater, the ORR was 59% with the dostarlimab combination (n = 71) and 39% with the pembrolizumab combination (n = 71). Here, the PFS was 10.4 months vs 6.1 months, respectively (HR, 0.66; 95% CI, 0.41-1.03).

For patients with a PD-L1 TPS of 1%-49%, the ORR was 50% with dostarlimab (n = 44) vs 34% with pembrolizumab (n = 44) and the PFS was 9.0 months vs 5.4 months (HR, 0.67; 95% CI, 0.38-1.19). Additionally, patients who had a TPS of 50% or more had an ORR of 74% with dostarlimab and chemotherapy (n = 27) vs 48% with pembrolizumab and chemotherapy (n = 27). In this group, the PFS was 10.4 months with dostarlimab and 6.7 months with pembrolizumab (HR, 0.60; 95% CI, 0.27-1.29).

Regarding safety, treatment-emergent adverse events (TEAEs) seen with dostarlimab were consistent with previous trials which evaluated similar regimens. For both the dostarlimab and pembrolizumab treatment arms, the rate of TEAEs was 97%. The rate of grade 3 or higher TEAEs was 59% with dostarlimab and 60% with pembrolizumab. Further, the most common TEAEs included anemia, asthenia, nausea, constipation, cough, dyspnea, vomiting, decreased appetite, and neutropenia.

“The head-to-head data from the PERLA trial showed that dostarlimab combined with chemotherapy provided robust anti-tumor activity in patients with previously untreated metastatic non-squamous non–small cell lung cancer. The positive results from this trial inform our future development plans and highlight the potential for dostarlimab to be our foundational immuno-oncology therapy as a single-agent and in combination with standards of care and novel therapies within our pipeline,” said Hesham Abdullah, senior vice president, global head of oncology development at GSK, in the press release.

REFERENCES:
PERLA phase II trial of Jemperli (dostarlimab) plus chemotherapy shows positive results in first-line metastatic non-squamous non-small cell lung cancer. News release. GSK. December 7, 2022. Accessed December 8, 2022. https://bit.ly/3W5Bm1v
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 December 8, 2022. https://clinicaltrials.gov/ct2/show/NCT04581824