Efficacy and safety of pralsetinib in <i>RET</i> fusion-positive solid tumors: Data from the TAPISTRY trial.

Abstract

184 Background: Pralsetinib is an oral tyrosine kinase inhibitor that selectively and potently targets oncogenic RET fusion and mutation proteins, present in multiple tumor types. We report results from the phase 2 TAPISTRY study (NCT04589845), a global, open-label, multicohort study evaluating the efficacy and safety of pralsetinib in a cohort of patients with RET fusion-positive solid tumors, including pancreatic, colorectal, and hepatobiliary cancers. Methods: Eligible patients were ≥12 years old with unresectable, locally advanced or metastatic RET fusion-positive solid tumors. Patients received 400mg pralsetinib QD until disease progression, loss of clinical benefit, or unacceptable toxicity. Independent review committee (IRC)-assessed objective response rate (ORR) was the primary endpoint. Key secondary endpoints included IRC-assessed duration of response (DOR) and progression-free survival (PFS), and overall survival (OS). Results: Forty-six patients were enrolled and received ≥1 pralsetinib dose; 78% had received ≤1 prior line of therapy in the metastatic setting. Median age was 56 y (range: 12-79); 61% were male. Median treatment duration was 14.3 mo (range: 0.7-31.5). Cancers included thyroid (n=18, 39%); colorectal (n=9, 20%); head and neck (n=4, 9%); pancreatic (n=4, 9%); hepatobiliary (n=3, 7%); CNS, neuroendocrine and adrenal, and sarcoma (n=2, 4% each); gastroesophageal (n=1, 2%); and unknown primary origin (n=1, 2%). ORR for the efficacy evaluable population (n=39) was 67% (95%CI: 50, 81), with 5 (13%) CRs (including 1 patient with colorectal cancer) and 21 (54%) PRs. Table shows efficacy outcomes for pancreatic, colorectal, and hepatobiliary tumors. All patients experienced treatment-related adverse events (TRAEs); 33/46 (72%) reported TRAEs grade ≥3. The most common TRAEs included anemia (n=18; 39%), increased AST (n=16; 35%), and decreased neutrophil count (n=13; 28%). Hypertension was reported in 11 (24%) patients, with 3 (7%) reporting grade ≥3. Safety results were consistent with the known profile for pralsetinib, with no new signals identified. Conclusions: Pralsetinib demonstrated robust and durable activity against RET fusion-positive solid tumors, including GI tumors, with an ORR of 67%. These data validate RET fusions as a tissue-agnostic target with sensitivity to RET inhibition, suggesting the potential therapeutic utility of pralsetinib in these patients. Clinical trial information: NCT04589845 . Efficacy summary. Overall(N=39) Pancreatic tumors(n=3) Colorectal tumors(n=8) Hepatobiliary tumors (n=3) ORR, % (95% CI) 67 (50, 81) 67 (9, 99) 38 (9, 76) 33 (1, 91) DOR, median, mo (95% CI) 26.7 (14.7, NE) 3.9 (3.7, NE) 12.2 (5.7, NE) 14.9 (NE) PFS, median, mo (95% CI) 16.5 (7.2, NE) 5.6 (1.9, NE) 6.5 (1.6, 12.9) 8.3 (1.4, NE) OS, median, mo (95% CI) 30.8 (16.3, NE) 21.7 (12.7, NE) 10.2 (5.7, NE) 13.8 (8.3, NE) Follow-up, median, mo (range) 14.5 (2, 32) 12.6 (2, 31) 9.2 (2-19) 8.3 (2, 19) NE, not evaluable.