Pralsetinib Shows Durable Anti-Tumor Activity in Study Update for RET+ Solid Tumors


Pralsetinib was well tolerated, while demonstrating robust and durable anti-tumor activity when treating heavily pretreated patients with multiple RET fusion–positive advanced solid tumors.

Pralsetinib (Gavreto) was well tolerated, while demonstrating robust and durable anti-tumor activity when treating heavily pretreated patients with multiple RET fusion–positive advanced solid tumors, according to an update of the ARROW trial (NCT03037385) presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

More than half of the patients on this trial achieved objective tumor responses. Of the evaluable patients, 89% experienced tumor shrinkage irrespective of their RET fusion partner. Furthermore, pralsetinib’s safety profile was consistent with previously reported data in the overall safety population and showed no new safety signals.

“These data highlight the need for broad RET testing to identify candidates who may benefit from pralsetinib,” Vivek Subbiah, MD, an associate professor in the Investigational Cancer Therapeutics department and director of the Clinical Center for Targeted Therapy, Cancer Medicine division at The University of Texas MD Anderson Cancer Center, said in his presentation.

This open-label, first-in-human trial investigated pralsetinib, a highly potent, selective RET inhibitor, at 30 to 600 mg by mouth daily or twice daily in the phase 1 dose escalation arm, which has been completed. The phase 2 dose expansion arm looked at 400 mg of pralsetinib by mouth daily. The primary end points in the expansion arm were overall response rate (ORR) by RECIST v1.1 and safety. Secondary end points included duration of response, progression-free survival, overall survival, clinical benefit rate (CBR), and disease control rate (DCR).

In the 19 evaluable patients, there was an ORR of 53% (95% CI, 29%-76%), with a complete response rate of 11% and partial response rate of 42%. There were 5 patients (26%) with stable disease and 4 patients (21%) with progressive disease. The CBR was 68% (95% CI, 43%-87%) and DCR was 79% (95% CI, 54%-94%).

Responses were observed across multiple tumor types, including 3 patients with pancreatic cancer. One of these patients had a CR at 20.8 months on pralsetinib. Two patients with unknown primary tumors, 2 with cholangiocarcinoma, 1 with a mesenchymal tumor, 1 with a salivary duct tumor, and 1 with a lung carcinoid tumor achieved response.

For the 21 patients evaluable for safety, most treatment-related adverse events (TRAEs) were grade 1 or 2. The most common any grade AEs were increased alanine aminotransferase at 43%, increased aspartate aminotransferase at 38%, and neutropenia and anemia both at 33%. Grade 3 or more AEs were most commonly neutropenia at 29%, anemia at 19%, and thrombocytopenia and hypertension both at 10%. TRAEs led to 1 patient discontinuing pralsetinib and 8 patients (38%) having dose reductions.

The median age on ARROW was 55 years (range, 31-71) and 62% were female. The ECOG performance status was either 0 in 33% or 1 in 67%. There were 19% of patients with a history of central nervous system metastases. The most common tumor type was lung cancer in 19% of patients.

“Of note, 9 patients had treatment refractory gastrointestinal cancers with limited therapy options that included pancreatic, cholangiocarcinoma, and colon cancer—3 of each,” Subbiah said. “The most common RET fusion partner was CCDC6 and KIF5B in 5 patients each. [Thirty-three percent of] patients received a prior multikinase inhibitor, 86% of patients received prior chemotherapy, and 10% of patients received prior immune checkpoint inhibitors.”

There were 8 patients each who received prior radiation therapy or prior cancer-related surgery. The median prior lines of therapy was 2 (range, 1-9). There were 13 patients (62%) who received 1 or 2 lines, 29% who received 3 or more, and 10% who received none.

The FDA approved pralsetinib based on results of the ARROW trial for adult and pediatric patients 12 years old or more, with advanced or metastatic RET-mutant medullary thyroid cancer or RET fusion–positive thyroid cancer.2 This trial is still enrolling patients with other RET fusion–positive solid tumors.1


1. Subbiah V, Cassier PA, Siena S, et al. Clinical activity and safety of the RET inhibitor pralsetinib in patients with RET fusion–positive solid tumors: update from the ARROW trial. Presented at: American Society of Clinical Oncology Annual Meeting; June 4-8, 2021; Virtual. Abstract 3079.

2. FDA approves pralsetinib for RET-altered thyroid cancers. FDA. Published December 1, 2020. Accessed June 4, 2021.

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