Abstract

3094 Background: Selpercatinib, a first-in-class highly selective and potent RET kinase inhibitor, is approved in multiple countries for the treatment of lung and thyroid cancer with RET fusions and medullary thyroid cancer with RET mutations. We provide an efficacy and safety update with more patients (pts) and longer follow-up (data cut-off: 24Sep2021) in RET fusion+ solid tumors with histologies other than lung/thyroid. Methods: The phase 1/2 LIBRETTO-001 trial (NCT03157128) enrolled pts with locally advanced/metastatic RET fusion+ solid tumors. Following dose escalation, pts received the recommended dose of 160 mg orally twice daily. The efficacy analysis set consisted of pts enrolled ≥6 months (mo) prior to the cut-off date. If a pt achieved response, an additional ≥6 mo follow-up from the initial response was required. There was no additional follow-up required for non-responders. Response was assessed per RECIST 1.1. Primary endpoint was objective response rate (ORR) by independent review committee (IRC). Secondary endpoints included ORR by investigator (INV), duration of response (DoR), progression-free survival (PFS), time to response (TTR), and safety. Results: Forty-five pts with 14 unique RET fusion+ tumor types received ≥1 dose of selpercatinib: 12 pancreatic, 10 colon, 4 salivary, 3 unknown primary, 3 sarcoma, 2 each of breast, carcinoma of the skin, xanthogranuloma, and cholangiocarcinoma, and 1 each of lung carcinoid, rectal neuroendocrine, small intestine, ovarian, and pulmonary carcinosarcoma. Median age was 53 years (range 21-85). Forty-one pts received prior systemic therapy (median prior lines: 2, range 0-9); 31% received ≥3 lines. In 41 efficacy-evaluable pts, confirmed ORR by IRC was 44% (18/41, 95% CI: 29-60). Clinical benefit was observed in 63% (26/41) of pts: 2 complete responses (breast, small intestine), 16 partial responses, and stable disease ≥16 weeks in 8 pts by IRC. Responses were observed across a variety of fusion partners. Median TTR was 1.9 mo by IRC. Median DoR was 24.5 mo (95% CI: 9.2-NE) with 50% (9/18) of responses ongoing at a median follow-up of 14.9 mo by IRC. Median PFS by IRC was 13.2 mo (95% CI: 7.4-26.2), with 34.1% alive and progression-free at a median follow-up of 16.4 mo. No new safety signals were identified in this cohort compared to broader safety database. Three grade 5 AEs were observed (unrelated to treatment by INV), and 4 pts discontinued treatment due to AEs (1 deemed related to treatment by INV). Conclusions: Selpercatinib continued to demonstrate durable antitumor activity in pts with RET fusion+ cancers across multiple tumor types. No new safety signals were identified. These results emphasize the importance of comprehensive genomic profiling to identify actionable oncogenic drivers, including RET fusions. The LIBRETTO-001 study continues to enroll pts. Clinical trial information: NCT03157128.