Rigel

Critical safety signal detected for pralsetinib in NSCLC trial

October 28, 2024

According to the DHCP letter, an ad hoc analysis for the currently active phase 3 AccelRET-Lung trial demonstrated a disproportionate risk for severe and fatal infection, including severe opportunistic infections, between the pralsetinib and standard-of-care (SOC) arms.

The ad hoc analysis was triggered by an observation of an imbalance in fatal adverse events between the two treatment arms, primary infections. Fatal adverse events were reported in 13% (14/108) of patients in the pralsetinib group vs. 4.8% (5/104) in the SOC group. Of these fatal events, fatal infection events occurred in 5 patients (4.6%) in the pralsetinib arm, and none in the SOC arm.

Additionally, the rate of severe (grade 3-5) infection events was significantly higher in the pralsetinib group vs. SOC (25.9% vs. 7.7%, respectively; P =.0004). The risk of severe infection was also significantly higher among pralsetinib recipients vs. those receiving SOC (risk ratio 3.33; 95% CI, 1.57-7.06).

Half of the severe infections reported in the pralsetinib group were lung infections and occurred in the first 66 days of treatment. Severe opportunistic infections (pneumocystis jirovecii pneumonia, cytomegalovirus pneumonia, legionella pneumonia, and esophageal candidiasis) were seen in 7 (6.5%) pralsetinib patients vs. 0 patients treated with SOC.

The letter is available on the Gavreto Healthcare Provider website.

Pralsetinib is approved for treating adults with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) and for adults and children ≥12 years with advanced or metastatic RET fusion-positive thyroid cancer requiring systemic therapy and refractory to radioactive iodine.

Source:

Rigel. (2024, October 24). Rigel Pharmaceuticals Issues Dear Healthcare Provider Letter for GAVRETO (pralsetinib). [Press release]. https://www.rigel.com/investors/news-events/press-releases/detail/398/rigel-pharmaceuticals-issues-dear-healthcare-provider