Pralsetinib, an oral tyrosine kinase inhibitor, selectively and potently targets oncogenic RET fusion and mutation proteins. Pralsetinib (GAVRETO) is FDA approved to treat adults with metastatic RET-altered NSCLC. Blueprint  entered into an agreement in 2020 with Roche (through Genentech in the US and its international division outside the US and Greater China) to develop GAVRETO for RET-altered cancers. But Roche’s decision to end its GAVRETO partnership in February 2023, effective February 2024. Roche handed all global rights back to Blueprint Medicines in February 2024, and Blueprint subsequently transferred the US commercial rights for GAVRETO to Rigel Pharmaceuticals.

At ASCO 2026, results from the Phase III (AcceleRET-Lung) study positioned Blueprint Medicines' pralsetinib as a potential new standard of care for first-line RET fusion–positive advanced or metastatic NSCLC. The trial demonstrated significant improvements in progression-free survival, objective response rate, and duration of response compared with platinum-based standard-of-care therapy, further reinforcing the value of precision-targeted treatment in this molecularly defined patient population. 

Key Efficacy Highlights (AcceleRET-Lung):

• Primary endpoint met: Pralsetinib significantly improved progression-free survival (PFS) versus platinum-based standard-of-care (SOC).

• Median PFS: 18.7 months vs. 9.0 months (HR = 0.59; p = 0.003), nearly doubling disease control duration.

• Objective Response Rate (ORR): 65.5% vs. 41.6% (p < 0.001).

• Median Duration of Response (DoR): 20.6 months vs. 9.7 months (HR = 0.48; p = 0.004).

• Overall Survival (OS): Not reached vs. 39.8 months.

Safety: Favorable Efficacy Profile with Important Infection Considerations:

• Safety profile was generally consistent with the known profile of pralsetinib.

• Higher infection rates were observed with pralsetinib (71.3% vs. 51.9%).

• Increased rates of Pneumonia (19.4% vs. 5.8%); Urinary tract infections (17.6% vs. 7.7%)

• Infection-related deaths: 8 cases in the pralsetinib arm versus none in the SOC arm.

• Most common Grade ≥3 treatment-related adverse events included: Hypertension (11.1%); Neutropenia (10.2%); Anemia (8.3%); Decreased neutrophil count (7.4%).

KOL insights

“The AcceleRET-Lung findings validate and extend the evidence generated by the ARROW study, further supporting pralsetinib as a first-line standard-of-care option for patients with RET fusion–positive advanced NSCLC, in alignment with current precision oncology treatment guidelines” –Expert Opinion

“Higher response rates and more durable responses observed with pralsetinib highlight its clinical value and reinforce the benefits of targeted RET inhibition over conventional chemotherapy”–Expert Opinion

Conclusion:

NSCLC is increasingly becoming a biomarker-driven market. RET rearrangements account for a small (~1-2% of NSCLC) but clinically significant proportion of NSCLC cases and have emerged as an important biomarker for targeted therapy. 

Pralsetinib (GAVRETO) was approved by the FDA in 2020 shortly after selpercatinib for RET fusion–positive NSCLC, with both agents demonstrating comparable overall response rates and activity in this biomarker-defined population. However, selpercatinib has generally shown a more robust and better-characterized clinical profile, particularly with respect to central nervous system (CNS) activity, making it a preferred option in patients with brain metastases. Despite its early clinical promise, GAVRETO’s commercial and development trajectory has been more limited, with declining sales in 2024 following the termination of Roche’s collaboration with Blueprint Medicines and subsequent restructuring of its global development strategy. As a result, its availability has become more restricted, with US access continuing through prescription channels via Rigel Pharmaceuticals, reflecting a narrowed but ongoing presence in the RET inhibitor landscape.

At ASCO 2026, the Phase III AcceleRET-Lung study demonstrated that pralsetinib significantly improved progression-free survival, response rates, and response durability compared with standard chemotherapy, reinforcing its potential as a frontline treatment option for RET fusion–positive advanced NSCLC. While careful monitoring for infections remains important, the study reinforces a critical message: comprehensive molecular testing is essential to identify eligible patients and ensure access to the most effective biomarker-driven therapies.