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PMID
Authors Vivek Subbiah, Mimi I-Nan Hu, Justin F. Gainor, Aaron Scott Mansfield, Guzman Alonso, Matthew H. Taylor, Viola Weijia Zhu, Pilar Garrido Lopez, Alessio Amatu, Robert C Doebele, Philippe Alexandre Cassier, Bhumsuk Keam, Martin H. Schuler, Hui Zhang, Corinne Clifford, Michael Palmer, Jennifer Green, Christopher D. Turner, Giuseppe Curigliano
Title Clinical activity of the RET inhibitor pralsetinib (BLU-667) in patients with RET fusion+ solid tumors.
Journal Journal of Clinical Oncology
Vol 38
Issue 15_suppl
Date
URL https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.109
Abstract Text Background: RET gene fusions are targetable oncogenic drivers in multiple tumor types, including up to 20% of papillary thyroid cancers (PTC). Pralsetinib is an investigational, highly potent, selective inhibitor of oncogenic RET alterations. In the registration-enabling Phase 1/2 ARROW study (NCT03037385), pralsetinib demonstrated an overall response rate (ORR; response-evaluable patients [REP], central review) of 73% (19/26) in treatment-naïve patients and 61% (49/80; 2 pending confirmation) in platinum-exposed patients with RET fusion+ non-small cell lung cancer (NSCLC) and was well tolerated (data cut-off November 18, 2019). We provide an update on the clinical activity of pralsetinib in other RET fusion+ solid tumor types. Methods: ARROW consists of a phase 1 dose escalation (30–600 mg once [QD] or twice daily) followed by a phase 2 expansion (400 mg QD) in patients with advanced RET-altered solid tumors. Primary objectives were ORR and safety. Results: As of November 18, 2019, 29 patients with metastatic solid tumor types other than NSCLC (16 PTC, 1 undifferentiated thyroid, 3 pancreatic, 3 colon, 6 other) bearing a RET fusion have received pralsetinib. Efficacy data are presented for REP enrolled by July 11, 2019. In patients with thyroid cancer that is RET fusion+, ORR (investigator assessment) was 75% (9/12; all confirmed). Median (range) duration of response (DOR) was 14.5 (3.7+, 16.8) months (mo), with 67% of responding patients continuing treatment. Two patients with stable disease were continuing treatment at 11.5+ and 19.3+ mo. In other RET fusion+ cancers, ORR was 60% (3/5; all confirmed) with partial responses in 2/2 patients with pancreatic cancer (DOR 5.5, 7.4+ mo) and 1 patient with intrahepatic bile duct carcinoma (DOR 7.5 mo). Two patients with colon cancer had stable disease for 7.3 and 9.3 mo. Responses were observed across multiple fusion genotypes. In the entire safety population (all patients treated with 400 mg QD pralsetinib, regardless of diagnosis; n = 354), most treatment-related adverse events (TRAEs) were grade 1-2, and included increased aspartate aminotransferase (31%), anemia (22%), increased alanine aminotransferase (21%), constipation (21%) and hypertension (20%). Only 4% of patients in the safety population discontinued due to TRAEs. Conclusions: Pralsetinib demonstrated broad and durable antitumor activity across multiple advanced solid tumor types, regardless of RET fusion genotype, and was well tolerated. The study is ongoing and still enrolling patients in this cohort. Clinical trial information: NCT03037385.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET fusion colon cancer predicted - sensitive Pralsetinib Case Reports/Case Series Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated, resulted in stable disease in 2 patients with RET fusion-positive colon cancer, with a duration of response of 7.3 and 9.3 months, respectively (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 109-109; NCT03037385). detail...
RET fusion Advanced Solid Tumor predicted - sensitive Pralsetinib Phase Ib/II Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated, resulted in an objective response rate of 60% (3/5) in patients with RET fusion positive advanced solid tumors other than thyroid cancer and non-small cell lung cancer (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 109-109; NCT03037385). detail...
RET fusion thyroid gland papillary carcinoma sensitive Pralsetinib Phase Ib/II Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated, resulted in an objective response rate of 75% (9/12) and a median duration of response of 14.5 months in patients with RET fusion positive papillary thyroid cancer (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 109-109; NCT03037385). detail...
RET fusion intrahepatic cholangiocarcinoma sensitive Pralsetinib Case Reports/Case Series Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated, resulted in a partial response in a patient with RET fusion-positive intrahepatic cholangiocarcinoma, with a duration of response of 7.5 months (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 109-109; NCT03037385). detail...
RET fusion pancreatic cancer predicted - sensitive Pralsetinib Case Reports/Case Series Actionable In a Phase I/II trial (ARROW), Gavreto (pralsetinib) treatment was well-tolerated, resulted in a partial response in 2 of 2 patients with RET fusion positive pancreatic cancer, with a duration of response of 5.5 and 7.4 months, respectively (J Clin Oncol 38, no. 15_suppl (May 20, 2020) 109-109; NCT03037385). detail...