Adding pegargiminase to standard frontline chemotherapy improves outcomes in patients with nonepithelioid pleural mesothelioma, according to study results presented at the AACR Annual Meeting 2023. 

Pegargiminase improved progression-free survival (PFS) and overall survival (OS) in this study, said presenter Peter W. Szlosarek, MD, PhD, of Barts Cancer Institute at Queen Mary University of London in the UK.

The phase 2/3 study (ATOMIC-Meso; Identifier: NCT02709512) enrolled 249 patients with nonepithelioid pleural mesothelioma. The patients’ median age was 71 (range, 28-86) years, and 82.7% were men. None of the patients had received prior systemic therapy, and most had received no prior surgery (85.1%) or radiation (94.8%). 

Patients were randomly assigned to receive pegargiminase plus chemotherapy (n=125) or placebo plus chemotherapy (n=124). Chemotherapy consisted of pemetrexed and cisplatin or carboplatin every 3 weeks for up to 6 cycles. Pegargiminase was given weekly at 36 mg/m2 with chemotherapy and as maintenance for up to 2 years.

The objective response rate was similar between the arms — 13.8% in the pegargiminase arm and 13.5% in the placebo arm. The disease control rate was numerically higher in the pegargiminase arm than in the placebo arm — 85.1% and 76.4%, respectively (P =.15).

The median OS was 9.3 months in the pegargiminase arm and 7.7 months in the placebo arm (hazard ratio [HR], 0.71; 95% CI, 0.55-0.93; P =.0234). The median PFS was 6.2 months and 5.6 months, respectively (HR, 0.65; 95% CI, 0.46-0.90; P =.0193).

Grade 3 or higher treatment-related adverse events (AEs) were reported in 28.8% of patients in the pegargiminase arm and 16.9% of those in the placebo arm.

The most common grade 3 or higher treatment-emergent AEs were blood and lymphatic system disorders, which occurred in 9.6% of patients in the pegargiminase arm and 4.0% of patients in the placebo arm.

Four patients in the pegargiminase arm had grade 3 or higher immune system disorders, which included 3 anaphylactic reactions.

“Pegargiminase-based chemotherapy represents the first new anti-metabolite regimen based on arginine deprivation for the treatment of cancer, and further studies of pegargiminase are warranted in arginine-dependent cancers,” Dr Szlosarek concluded.

Disclosures: This research was supported by Polaris Pharmaceuticals, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Szlosarek PW, Creelan B, Sarkodie T, et al. Phase 2-3 trial of pegargiminase plus chemotherapy versus placebo plus chemotherapy in patients with non-epithelioid pleural mesothelioma. AACR 2023. April 14-19, 2023. Abstract CT007.

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