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

3144 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. Methods: Eligible patients ≥12 years old with unresectable, locally advanced or metastatic RET fusion-positive solid tumors received 400 mg pralsetinib QD until disease progression, loss of clinical benefit, or unacceptable toxicity. Independent review committee (IRC)-assessed objective response rate (ORR) was the primary end point. Key secondary end points 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 ≤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, sarcoma, and neuroendocrine and adrenal (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; Table), with 5 (13%) CRs and 21 (54%) PRs. Intracranial response was observed in 1/2 (50%) patients with baseline CNS metastases. 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 pralsetinib profile, with no new signals. Conclusions: Pralsetinib demonstrated robust and durable activity against RET fusion-positive solid tumors, with an ORR of 67%. These data validate RET fusions as a tissue-agnostic target with sensitivity to RET inhibition, suggesting therapeutic utility of pralsetinib. Clinical trial information: NCT04589845 . Efficacy summary by tumor type. Overall(N=39) Thyroid (n=16) Pancreatic (n=3) Colorectal (n=8) Hepatobiliary (n=3) Head and Neck (n=3) ORR, % (95% CI) 67(50, 81) 81(54, 96) 67(9, 99) 38(9, 76) 33(1, 91) 100(29, 100) DOR, median, mo (95% CI) 26.7(14.7, NE) 26.7(26.7, NE) 3.9(3.7, NE) 12.2(5.7, NE) 14.9(NE) NE PFS, median, mo (95% CI) 16.5(7.2, NE) 30.3(16.3, NE) 5.6(1.9, NE) 6.5(1.6, 12.9) 8.3(1.4, NE) NE OS, median, mo (95% CI) 30.8(16.3, NE) NE(NE) 21.7(12.7, NE) 10.2(5.7, NE) 13.8(8.3, NE) NE Follow-up, median, mo (range) 14.5(2, 32) 19.4(10, 32) 12.6(2, 31) 9.2(2, 19) 8.3(2, 19) 14.3(14, 27) NE, not evaluable.