LOXO-260 / Eli Lilly - LARVOL DELTA

Review and analysis of clinical trials of selective RET inhibitors for the treatment of thyroid cancer. (PubMed, Front Oncol) - "Selpercatinib and pralsetinib are the most frequently studied RET inhibitors. Notably, research on next-generation RET inhibitors as monotherapy approaches (e.g., LOXO-260, enbezotinib, SY-5007 and TY-1091) is currently underway...While selective RET inhibitors have demonstrated therapeutic potential, concerns regarding drug resistance and toxicity persist. Therefore, future strategies should prioritize the development of next-generation inhibitors and the optimization of combination regimens to improve outcomes for RET-altered thyroid cancer patients."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma • RET

LOXO-NGR-21001: A Study of LOXO-260 in Cancer Patients With a Change in a Particular Gene (RET) That Has Not Responded to Treatment (clinicaltrials.gov) - P1 | N=70 | Active, not recruiting | Sponsor: Eli Lilly and Company | N=110 ➔ 70

Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

LOXO-NGR-21001: A Study of LOXO-260 in Cancer Patients With a Change in a Particular Gene (RET) That Has Not Responded to Treatment (clinicaltrials.gov) - P1 | N=110 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Endocrine Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

First-in-human, phase 1 study of a selective RET inhibitor, LOXO-260, in patients with RET inhibitor refractory, RET-altered cancers (EORTC-NCI-AACR 2024) - P1 | "LOXO-260 demonstrated a manageable safety profile but clinical activity was limited to patients with acquired SF mutations. The rarity of SF mutations and the diversity of bypass mutations may limit the clinical impact of next-generation RET inhibitors for selpercatinib resistance."

Clinical • P1 data • Endocrine Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Thyroid Gland Papillary Carcinoma • RET

A Study of LOXO-260 in Cancer Patients With a Change in a Particular Gene (RET) That Has Not Responded to Treatment (clinicaltrials.gov) - P1 | N=110 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial primary completion date: Jun 2025 ➔ Sep 2024

Trial primary completion date • Endocrine Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

A Study of LOXO-260 in Cancer Patients With a Change in a Particular Gene (RET) That Has Not Responded to Treatment (clinicaltrials.gov) - P1 | N=110 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2026 ➔ Jun 2025 | Trial primary completion date: Apr 2026 ➔ Jun 2025

Enrollment closed • Trial completion date • Trial primary completion date • Endocrine Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET

Eli Lilly axes next-generation, resistance-busting RET inhibitor (FierceBiotech) - "Eli Lilly has axed its next-generation RET inhibitor. The Big Pharma pushed the candidate, LOXO-260, into the clinic to overcome acquired resistance to existing drugs such as its own Retevmo but has now pulled it from the pipeline before clearing phase 1...While the government website, which was last updated in August, still lists the trial as enrolling, Lilly removed (PDF) the RET inhibitor from its pipeline as part of its fourth-quarter results this morning. LOXO-260 was the only new drug removed from the pipeline. Lilly also dropped Verzenio in prostate cancer."

Discontinued • Trial termination • Metastatic Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer • Solid Tumor

A first-in-human phase 1 study of the next-generation RET inhibitor, LOXO-260, in RET inhibitor refractory patients with RET-altered cancers (trial in progress). (ASCO 2022) - P1 | "Selpercatinib was the first selective RET inhibitor approved by the FDA and is indicated for patients (pts) with RET fusion-positive NSCLC and thyroid cancer, and RET mutant MTC. Pts must be ≥18 years old and have an ECOG PS of 0-2. Key exclusion criteria include presence of serious cardiac conditions, interstitial lung disease, symptomatic CNS metastases, or carcinomatous meningitis."

Clinical • P1 data • CNS Disorders • Endocrine Cancer • Infectious Disease • Interstitial Lung Disease • Lung Adenocarcinoma • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • Thyroid Gland Papillary Carcinoma • RET

Improving Outcomes for Patients With NSCLC and RET Alterations (Targeted Oncology) - "Nathan A. Pennell, MD...discusses the importance of developing new RET inhibitors for patients with non–small cell lung cancer (NSCLC)....There are no next-line options for these patients besides standard chemotherapy regimens for advanced NSCLC, which have limited efficacy in later lines of therapy."

Video

Trial of New RET Inhibitor Aims to Overcome Resistance in NSCLC and MTC (Target Oncol) - "Nathan Pennell, MD, PhD, discusses a first-in-human trial of a novel RET inhibitor for patients with non-small cell lung cancer and medullary thyroid cancer...The dose expansion part will measure the antitumor activity and pharmacokinetics of this agent based on progression-free survival, time to response, and duration of response."

Video

A Study of LOXO-260 in Cancer Patients With a Change in a Particular Gene (RET) That Has Not Responded to Treatment (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Medullary Carcinoma • RET