Innovent Biologics, Inc...is pleased to see that the National Medical Products Administration (NMPA) of China has approved the New Drug Application (NDA) for selpercatinib (40mg & 80mg capsules) for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion...

Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test

On March 11, the Ministry of Food and Drug Safety authorized the use of Lilly’s Retevmo in adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), adults and pediatric patients 12 years of age or older with advanced or metastatic RET-mutated medullary thyroid cancer requiring systemic therapy...The approval for Retevmo was based on the LIBRETTO-001 trial in RET-mutated advanced or metastatic solid cancer patients.

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has granted conditional marketing authorisation for Retsevmo® (selpercatinib) as monotherapy for several RET-driven advanced lung and thyroid cancers....The treatment was approved for...adults with advanced RET fusion positive non-small cell lung cancer (NSCLC) who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy

Retsevmo as monotherapy is indicated for the treatment of adults with...advanced RET fusion-positive non-small cell lung cancer (NSCLC) who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.

The UK's National Institute for Health and Care Excellence (NICE) on Thursday recommended Eli Lilly's Retsevmo (selpercatinib) be provided to treatment naïve RET fusion-positive advanced non-small cell lung cancer patients in England through the Cancer Drugs Fund.

Selpercatinib is recommended for use within the Cancer Drugs Fund as an option for treating RET fusion-positive advanced non-small-cell lung cancer (NSCLC) in adults who need systemic therapy after immunotherapy, platinum-based chemotherapy or both.

Treatment with selpercatinib led to significantly longer progression-free survival than platinum-based chemotherapy with or without pembrolizumab among patients with advanced RET fusion-positive NSCLC.

Eli Lilly and Company (NYSE: LLY) today announced topline results from the LIBRETTO-431 study evaluating Retevmo versus platinum-based chemotherapy plus pemetrexed – with or without pembrolizumab – as an initial treatment for patients with rearranged during transfection (RET) fusion-positive advanced or metastatic non-small cell lung cancer (NSCLC). The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS). This result was based on a pre-specified interim efficacy analysis conducted by an independent data monitoring committee (IDMC).

...Staging will be according to the Tumor, Node, Metastasis staging system for lung cancer-Must have an activating RET gene fusion in tumor based on polymerase chain reaction (PCR) or next generation sequencing (NGS)-Must have received definitive locoregional therapy with curative intent (surgery or radiotherapy) for Stage IB, II, or IIIA NSCLC-Patients must have completely recovered from definitive therapy (surgery or radiotherapy) as well as adjuvant therapy at the time of randomization-Must have Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1-Adequate hematologic, hepatic and renal function-Willingness of men and women of reproductive potential to observeconventional and effective birth control for the duration of treatment and for 2 weeks after. ...

...Identity of RET gene fusions, mutations, and concurrently activated oncogenic pathways in tumor biopsies and cfDNA. Cohorts 1 and 2: enrollment will be restricted to patients with evidence of a RET gene alteration in tumor...MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval...

Relative to patients in the comparator arm, patients in the selpercatinib arm had a longer TTD (HR: 0.26; 95% CI: 0.18, 0.38), TTNT-D (HR: 0.13; 95% CI: 0.07, 0.24), and TTP (HR: 0.42; 95% CI: 0.29, 0.61)….Findings from this post hoc case-matched effectiveness analysis using data from the LIBRETTO-001 trial suggest improved effectiveness associated with 1L use of selpercatinib versus 1L standard therapies in patients with RET fusion-positive aNSCLC.

In a large cohort with extended follow-up, selpercatinib continued to demonstrate durable and robust responses, including intracranial activity, in previously treated and treatment-naive patients with RET fusion–positive NSCLC.

Of the 169 RET fusion+ NSCLC pts who progressed per INV assessment, 120 (71%) continued selpercatinib post-progressive disease...In this posthoc analysis, a subset of pts with RET fusion+ NSCLC appear to derive ongoing clinical benefit from continuing selpercatinib treatment beyond PD.

In this open-label, multicenter, phase II study (NCT04280081), patients with advanced RET-altered solid tumors received selpercatinib….Efficacy against NSCLC was assessed in the primary analysis set (PAS; centrally confirmed RET status) and in all enrolled patients with NSCLC....ORR in the PAS (n = 26) was 69.2% [95% confidence interval (CI), 48.2-85.7] and 94.4% of responses were ongoing; the ORR was 87.5% and 61.1% in treatment-naïve and pre-treated patients, respectively. IRC-assessed ORR in all patients with NSCLC (n = 47) was 66.0% (95% CI, 50.7-79.1)....Selpercatinib, with potent and durable antitumor activity including intracranial activity, was well tolerated in Chinese patients with RET fusion-positive NSCLC...

The objective response rate was 55.3%(95% confidence interval: 38.3, 71.4; one confirmed complete response, 20 confirmed partial responses)in 38 evaluable patients in cohort 1 who could be followed for ≥2 post-baseline scans….Selpercatinib appeared to be effective in Japanese patients with RET fusion-positive NSCLC, and the safety profile was not substantially different from published results.

Among all NSCLC pts, 26 had measurable CNS metastases at baseline per IRC. Selpercatinib treatment resulted in a CNS ORR of 84.6% (95% CI: 65.1e95.6), with a CNSmDoR of 9.4 mo (95%CI: 7.4e15.3) at a median f/u of 25.8 mo. In the safety population (NSCLC pts with1 dose, N¼356)...With longer follow-up and additional patients, selpercatinib demonstrates durable efficacy and intracranial activity regardless of line of therapy.

Herein, we present results from LIBRETTO-321 (NCT04280081), the first study to evaluate the efficacy and safety of selpercatinib in Chinese patients with RET fusion-positive NSCLC….Among all response evaluable patients with NSCLC (n=45) after a median follow-up of 10.4 months the IRC-assessed ORR was 66.7% (95% CI, 51.0-80.0). Among five patients with measurable CNS metastasis at baseline, four (80%) achieved an IRC-assessed objective intracranial response and all of them had sustained responses at 9 months....Selpercatinib had robust and durable anti-tumor activity in Chinese patients with advanced RET fusion-positive NSCLC and was well-tolerated, consistent with previously reported results from LIBRETTO-001.

In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.

In this pre-planned analysis of RET fusion-positive NSCLC patients with baseline intracranial metastases...Among 22 patients with measurable intracranial disease at baseline, intracranial ORR was 82% (95%CI=60-95), including 23% with complete responses....In all 80 patients, median intracranial PFS was 13.7 months (95%CI=10.9-NE) at a median duration of follow-up of 11.0 months (IQR=7.4,16.5)....Selpercatinib has robust and durable intracranial efficacy in RET fusion-positive NSCLC patients.

The ORR with selpercatinib was 57% in the IAS, 64% in the PAS, and 85% in the treatment-naïve population...In both the IAS and PAS, the median DoR was 17.5 months, median PFS was 19.3 months at median follow-up of 12.0 and 15.7 months, respectively....In this updated data set, selpercatinib continued to demonstrate durable antitumor activity in pts with RET-fusion+ NSCLC.

In this heavily pretreated population of East Asian patients with RET fusion-positive NSCLC, treatment with selpercatinib resulted in a marked and durable tumor response…

...trial enrolled patients with advanced RET-altered solid tumors, including patients with RET fusion-positive advanced NSCLC with baseline CNS metastases. The selpercatinib recommended phase 2 dose was 160 mg twice daily, dosed orally in 28-day cycles....The intracranial ORR in the 14 patients was 93% (n = 13; 95% CI = 66.1 – 99.8), including 2 complete responses (14%) and 11 partial responses (79%)....Selpercatinib had marked intracranial anti-tumor activity in RET fusion-positive NSCLC patients with CNS metastases.

...RET fusion+ NSCLC and papillary thyroid cancer (PTC), RET-mutant medullary thyroid cancer (MTC)...The ORR in evaluable RET fusion+ pts was...65% (n = 17/26) in NSCLC and 83% (n = 5/6) in PTC.

Selpercatinib had durable efficacy, including intracranial activity, with mainly low-grade toxic effects in patients with RET fusion–positive NSCLC who had previously received platinum-based chemotherapy and those who were previously untreated.

We report a sixty-seven-old year man diagnosed with adenocarcinoma T1cN3M1a, stage IVA….After a recent bronchoscopic re-biopsy, RET fusion was detected by gene panel test. Subsequent administration of the molecular-targeted drug selpercatinib, was highly effective for the primary lesion and all metastatic lesions including brain metastases.