The PERLA trial results demonstrated that Dostarlimab plus chemotherapy achieved better overall survival (OS) compared to pembrolizumab plus chemotherapy in advanced non-small cell lung cancer (NSCLC), with a median OS of 20.2 months vs. 15.9 months.

PERLA Trial Overview

The PERLA trial, a Phase II study (NCT04581824), presented its latest findings at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting. The trial enrolled 243 patients with advanced NSCLC, randomized 1:1 to receive either:

• Dostarlimab (500 mg IV) + chemotherapy (Q3W) (n=121), or

• Pembrolizumab (200 mg IV) + chemotherapy (Q3W) (n=122).

The primary endpoint was objective response rate (ORR) as assessed per RECISTv1.1 by blinded independent central review. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety.

Patient Characteristics:

• Median age: 64 years (Dostarlimab) vs. 65 years (Pembrolizumab).

• Majority were male: 70% vs. 63%.

• ECOG performance status of 1: 69% vs. 59%.

• Brain metastases: 18% vs. 12%.

• Majority enrolled from Europe: 51% vs. 53%.

OS Outcomes

Dostarlimab plus chemotherapy showed a numerical advantage in OS compared to pembrolizumab plus chemotherapy.

• Median follow-up: 31.1 months (Dostarlimab) vs. 31.9 months (Pembrolizumab).

• Median OS:

o 20.2 months (95% CI: 14.5–27.3) for Dostarlimab.

o 15.9 months (95% CI: 11.6–19.3) for Pembrolizumab.

o HR=0.74 (95% CI: 0.54–1.00).

Survival Rates:

• 12-month OS: 63% (Dostarlimab) vs. 58% (Pembrolizumab).

• 18-month OS: 51% vs. 43%.

• 24-month OS: 46% vs. 33%.

• 30-month OS: 40% vs. 27%.

OS by PD-L1 Status

PD-L1 Tumor Proportion Score (TPS) analysis revealed:

1. TPS <1%:

o Dostarlimab: 20.8 months (95% CI: 11.4–NR).

o Pembrolizumab: 16.1 months (95% CI: 11.5–20.1).

2. TPS ≥1%:

o Dostarlimab: 19.4 months (95% CI: 10.6–31.2).

o Pembrolizumab: 15.9 months (95% CI: 7.8–22.2).

3. TPS 1–49%:

o Dostarlimab: 17.1 months (95% CI: 9.5–27.3).

o Pembrolizumab: 14.5 months (95% CI: 6.5–NR).

4. TPS ≥50%:

o Dostarlimab: Not Reached (NR) (95% CI: 9.9–NR).

o Pembrolizumab: 17.6 months (95% CI: 6.2–32.3).

Treatment Status and Safety

• Patients continuing treatment: 36% (Dostarlimab) vs. 21% (Pembrolizumab).

• Patients completing treatment: 64% vs. 79%.

• Deaths from any cause: 61% (Dostarlimab) vs. 73% (Pembrolizumab).

• Withdrawals: 2% vs. 6%.

Adverse Events (AEs):

• Any-grade AEs: 98% (both groups).

• Treatment-related AEs: 85% (Dostarlimab) vs. 81% (Pembrolizumab).

• Grade ≥3 AEs: 65% vs. 66%.

• Fatal AEs: 12% vs. 10%.

“Updated OS analyses reinforce earlier observations, demonstrating comparable efficacy and safety data between Dostarlimab plus chemotherapy and pembrolizumab plus chemotherapy,” said Dr. Solange Peters, Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV). “Notably, the Dostarlimab combination continued to show a numerical OS advantage.”

The results highlight Dostarlimab’s potential as a viable first-line option for advanced NSCLC patients, supporting ongoing research into its broader clinical application.