AcceleRET-Lung Trial

Design - Phase 3, randomized, open-label: first-line pralsetinib (selective oral RET inhibitor) vs platinum-based standard-of-care chemotherapy (with optional IO) in advanced/metastatic RET fusion-positive NSCLC. Presented at ASCO 2026 (Abstract 8504, oral) by Prof. Sanjay Popat.

PFS (primary endpoint) - Median PFS 18.7 vs 9.0 months (p=0.003) - a more than 2x improvement over chemotherapy, and the first Phase 3 confirmation that selective RET inhibition outperforms chemotherapy in the 1L setting (Rigel press release, May 21, 2026).

Response and duration - ORR 65.5% vs 41.6%; median duration of response 20.6 vs 9.7 months - more than doubled, flagged by KOLs as the most clinically meaningful signal beyond the headline PFS result (ASCO 2026 Abstract 8504).

Safety - Generally well-tolerated, consistent with prior single-arm studies, but with a notable infection signal: 30 deaths (30.0%) on pralsetinib vs 26 (25.0%) on SOC, including 8 (7.4%) infection deaths on pralsetinib vs 0 on SOC. The presentation suggested increased monitoring can manage severe infection risk. OS data were immature at cutoff.

Regulatory / sponsor - Pralsetinib (Gavreto) holds regular (traditional) FDA approval for metastatic RET fusion-positive NSCLC - accelerated approval September 2020 (ARROW), converted to regular approval August 9, 2023 on expanded ARROW data. AcceleRET-Lung adds randomized Phase 3 first-line evidence (ASCO 2026, Abstract 8504). Registry lead sponsor: Hoffmann-La Roche; US rights now held by Rigel Pharmaceuticals (acquired from Blueprint Medicines).

Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated August 19, 2026.

Progression-Free Survival (Primary Endpoint)

First-line pralsetinib produced a more than 2× improvement in median progression-free survival vs platinum-based SOC: mPFS 18.7 vs 9.0 months (p=0.003) in treatment-naïve RET fusion-positive advanced NSCLC. This is the first Phase 3 confirmation that selective RET inhibition outperforms chemotherapy in the 1L setting, validating earlier accelerated-approval data and establishing pralsetinib as a 1L option for this oncogene-defined subgroup.

Response Rate & Duration

Pralsetinib delivered a substantially higher and far more durable response than chemotherapy. ORR 65.5% vs 41.6% (pralsetinib vs SOC) and median DOR 20.6 vs 9.7 months. KOLs flagged the magnitude of DOR improvement — more than doubling — as the most clinically meaningful signal beyond the headline PFS result.

Safety & Tolerability

Pralsetinib was generally well-tolerated with a profile consistent with prior single-arm studies. KOLs highlighted a notable infection signal: 30 deaths (30.0%) in the pralsetinib arm vs 26 (25.0%) in SOC, with 8 (7.4%) due to infection on pralsetinib vs 0 on SOC. The Rigel presentation suggested increased monitoring is sufficient to manage severe infection risk in practice. Overall survival data remained immature at the data cutoff.

What is the AcceleRET-Lung trial?

AcceleRET-Lung (NCT04222972) is a Phase 3, randomized, open-label trial comparing pralsetinib (Gavreto), a selective oral RET kinase inhibitor, against platinum-based standard-of-care chemotherapy (with optional immunotherapy) as first-line treatment of advanced or metastatic RET fusion-positive NSCLC. Results were presented at ASCO 2026 (Abstract 8504) by Prof. Sanjay Popat of the Royal Marsden.

What did AcceleRET-Lung show?

The trial met its primary endpoint: first-line pralsetinib more than doubled median progression-free survival versus chemotherapy - 18.7 vs 9.0 months (p=0.003). ORR was 65.5% vs 41.6%, and median duration of response was 20.6 vs 9.7 months. Overall survival data remained immature at the data cutoff.

Is pralsetinib (Gavreto) FDA approved?

Yes. Pralsetinib received FDA accelerated approval in September 2020 for metastatic RET fusion-positive NSCLC based on the Phase 1/2 ARROW study, and the FDA converted this to regular (traditional) approval on August 9, 2023 based on data from additional ARROW patients and longer follow-up. AcceleRET-Lung adds randomized Phase 3 evidence versus platinum-based chemotherapy in the first-line setting. Pralsetinib is marketed in the US by Rigel Pharmaceuticals.

What safety signal was seen in AcceleRET-Lung?

Pralsetinib was generally well-tolerated with a profile consistent with prior single-arm studies, but KOLs highlighted an infection signal: 30 deaths (30.0%) in the pralsetinib arm versus 26 (25.0%) with standard of care, including 8 deaths (7.4%) due to infection on pralsetinib versus 0 on chemotherapy. The presentation suggested increased monitoring is sufficient to manage severe infection risk in practice.

Why is AcceleRET-Lung important?

It is the first Phase 3 randomized confirmation that a selective RET inhibitor outperforms platinum-based chemotherapy in first-line RET fusion-positive NSCLC, adding randomized evidence on top of the ARROW data that earned pralsetinib accelerated (2020) and then regular (2023) FDA approval. The near-doubling of PFS and more-than-doubled duration of response solidify pralsetinib as a first-line option for this oncogene-defined subgroup.