MedPath

Entrectinib

Generic Name
Entrectinib
Brand Names
Rozlytrek
Drug Type
Small Molecule
Chemical Formula
C31H34F2N6O2
CAS Number
1108743-60-7
Unique Ingredient Identifier
L5ORF0AN1I
Background

Entrectinib is a tropomyosin receptor tyrosine kinase (TRK) TRKA, TRKB, TRKC, proto-oncogene tyrosine-protein kinase ROS1, and anaplastic lymphoma kinase (ALK) inhibitor. It was approved by the FDA in August 2019 for use in the treatment of ROS1-positive metastatic non-small cell lung cancer and NTRK gene fusion positive solid tumors. Entrectinib's approved use is meant as a last line of therapy due to its accelerated approval based on early trial data. This therapy offers benefit over similar ALK inhibitors such as alectinib, ceritinib, and lorlatinib due to a wider range of targets.

Indication

Entrectinib is indicated for the treatment of metastatic ROS1-positive non-small cell lung cancer in adults. Entrectinib is also indicated in adults and children over 12 years old for the treatment of NTRK gene fusion-positive solid tumors which have metastasized or for which surgical resection is likely to result in severe morbidity and for which has progressed on previous therapies or for which no comparable alternative therapies are available.

FoundationOne®Liquid CDx is the only FDA-approved test for the detection of ROS1 rearrangement(s) in NSCLC for selecting patients for treatment with entrectinib.

Associated Conditions
Metastatic Non-Small Cell Lung Cancer, Metastatic Solid Neoplasm, Solid Tumors
Clinical Trials
Related News

ROSALINE Trial: Neoadjuvant Letrozole/Entrectinib Shows Limited Efficacy in Invasive Lobular Breast Cancer

• The phase 2 ROSALINE trial found that combining entrectinib with letrozole failed to meet its primary endpoint, with no efficacy-evaluable patients achieving residual cancer burden (RCB) of 0 or 1 in invasive lobular breast cancer. • Despite the primary endpoint failure, the treatment showed a 49% objective response rate by MRI assessment, with 10% complete responses and 39% partial responses among the 41 evaluable patients. • ROSALINE represents the first neoadjuvant endocrine therapy trial dedicated exclusively to invasive lobular breast cancer, demonstrating the feasibility of subtype-specific trials while researchers continue biomarker analyses.

US Orphan Drug Market Set to Exceed $190 Billion by 2030 as FDA Designations Accelerate

• The US orphan drug market is projected to surpass $190 billion by 2030, with over 7,300 molecules receiving FDA Orphan Drug Designation to date, of which approximately 17.9% have gained approval. • Since 2020, more than half of all new drug approvals by the FDA's Center for Drug Evaluation and Research have been granted orphan status, highlighting the growing importance of rare disease treatments in pharmaceutical development. • Despite criticism over high pricing, exemplified by Abeona Therapeutics' Zevaskyn at $3.1 million per treatment, the orphan drug model has evolved into a sound business strategy offering fewer competitors, faster approvals, and seven-year market exclusivity.

Bayer's Vitrakvi Makes History as First Tumor-Agnostic Drug Approved in European Union

• The European Medicines Agency (EMA) has approved Vitrakvi (larotrectinib) as the first-ever tumor-agnostic therapy, treating cancers based on molecular signatures rather than tumor location. • The drug targets rare NTRK gene fusion cancers affecting several thousand European patients annually, particularly prevalent in sarcomas, brain, kidney, and thyroid cancers. • Bayer's Vitrakvi leads the European market ahead of competitor Roche's Rozlytrek, with approvals already secured in the US, Brazil, and Canada.

Experts Address Key Challenges in Implementation of Tumor-Agnostic Therapies and Genetic Testing

• The increasing adoption of tumor-agnostic therapies has highlighted the need for universal genetic testing in oncology practices, with eight drugs now holding FDA pan-tumor approvals as of January 2025. • Healthcare providers face complex decisions regarding genetic testing methodologies, including choices between tissue and liquid biopsies, timing of collection, and interpretation of results. • Clinical implementation challenges include establishing efficient testing workflows, securing genetic counseling resources, and determining appropriate treatment sequencing in cases with limited tumor-specific data.

Nuvation Bio's Taletrectinib Gains FDA Priority Review and Expanded Access Program for ROS1+ NSCLC

• The FDA granted priority review to Nuvation Bio's NDA for taletrectinib, a next-generation ROS1 inhibitor, for advanced ROS1+ non-small cell lung cancer, setting a PDUFA date of June 23, 2025. • Taletrectinib demonstrated promising efficacy and tolerability in the TRUST-I and TRUST-II trials, showing durable responses and prolonged progression-free survival in ROS1+ NSCLC patients. • Nuvation Bio has initiated an Expanded Access Program (EAP) in the U.S. for taletrectinib, offering access to eligible patients with advanced ROS1+ NSCLC outside of clinical trials. • The NDA is based on pooled data from the TRUST-I and TRUST-II studies, which included over 300 patients, representing the largest ROS1-positive NSCLC dataset supporting an NDA.

Zongertinib Shows Promise in HER2-Mutated NSCLC, Gains Breakthrough Therapy Designation

• Zongertinib (BI 1810631) receives breakthrough therapy designation from the FDA and China for HER2-mutated NSCLC, potentially filling a critical treatment gap. • Phase 1b Beamion LUNG-1 trial data reveals a 66.7% objective response rate in previously treated patients with HER2-mutated NSCLC at the 120mg dosage. • The TKI demonstrates activity against brain metastases, with objective response rates of 33% (120 mg) and 40% (240 mg) in patients with asymptomatic brain metastases. • Zongertinib shows a favorable tolerability profile, with low rates of dose reduction and treatment discontinuation in clinical trials.
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