08 May VITRAKVI® (larotrectinib) in Patients with Cancer and NTRK Gene Fusions

MedicalResearch.com Interview with:

Dr. Hong

David S Hong, M.D
Department of Investigational Cancer Therapeutics
Division of Cancer Medicine
MD Anderson, University of Texas

MedicalResearch.com: What is the background for this study?

Response: Larotrectinib is a first-in-class, CNS active, oral TRK inhibitor exclusively designed to treat tumors with an NTRK gene fusion and does not have secondary targets.

In previous presentations and published in The Lancet Oncology, larotrectinib demonstrated tumor-agnostic efficacy in an integrated dataset of 159 adult and pediatric patients with TRK fusion cancer across three clinical trials (Feb 2019 data cut-off date). In these studies, the objective response rate (ORR), according to investigator assessment, was 79% (95% confidence interval [CI], 72 – 85%), with a complete response rate of 16%.

A variety of NTRK genes have been identified in various tumor types including fusions and non-fusions (e.g., amplifications, rearrangements, deletions, slice variants). In the analysis presented at AACR 2020, we sought to evaluate this pooled data to determine the efficacy of larotrectinib in patients with non-fusion alterations in NTRK genes. 

MedicalResearch.com: What are the main findings?

Response: The ORR in patients treated with larotrectinib who have NTRK gene fusions was 79% (95% CI 72-85); with 24 patients achieving a complete response, 97 patients a partial response and 19 patients stable disease.

The ORR in patients treated with larotrectinib who do NOT have NTRK gene fusions was 1% (95% CI 0-7); with no patients achieving a complete response, 1 patient a partial response and 17 patients stable disease.

Across both fusion and non-fusion groups, larotrectinib was well tolerated with adverse events being primarily Grade 1 or 2.

MedicalResearch.com: What should readers take away from your report?

Response: The new analysis presented at AACR 2020 further illustrate larotrectinib is efficacious and durable in patients with TRK fusion cancer and highly selective towards NTRK gene fusions.

These data demonstrate the importance of proper patient identification and treatment with larotrectinib for patients with NTRK gene fusions and further underscore the urgency to implement genomic cancer testing following a cancer diagnosis. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: This analysis brings valuable insights into the selectivity of larotrectinib and the role of inhibiting active TRK signaling, which results from NTRK gene fusions.

As the only method to uncover NTRK gene fusions is through genomic cancer testing, future research focusing on the benefits of introducing genomic testing earlier in a cancer diagnosis would help guide treatment approach and implement the shift towards precision medicine in oncology in day-to-day practice. 

David S. Hong Disclosures (last 36 months)

• Research/Grant Funding: AbbVie, Adaptimmune, Aldi-Norte, Amgen, Astra-Zeneca, Bayer, BMS, Daiichi-Sankyo, Eisai, Fate Therapeutics, Genentech, Genmab, GSK, Ignyta, Infinity, Kite, Kyowa, Lilly, LOXO, Merck, MedImmune, Mirati, miRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pfizer, Seattle Genetics, Takeda, Turning Point Therapeutics
• Travel, Accommodations, Expenses: Bayer, LOXO, miRNA, Genmab, AACR, ASCO, SITC
• Consulting or Advisory Role: Alpha Insights, Amgen, Axiom, Adaptimmune, Baxter, Bayer, eCancer, Genentech, GLG, Group H, Guidepoint, Infinity, Medscape, Numab, Oncology Education Project Association, Pfizer, Prime Oncology, Takeda, Trieza Therapeutics, WebMD
• Other ownership interests: Molecular Match (Advisor), OncoResponse (Founder), Presagia Inc (Advisor)

Citation:

AACR Virtual Meeting 2020

CT062 – Efficacy and safety of larotrectinib in patients with cancer and NTRK gene fusions or other alterations
April 28, 2020

David S. Hong, Afshin Dowlati, Howard Burris, Edward Chu, Marcia S. Brose, Anna F. Farago, Cornelis M. Van Tilburg, Shivaani Kummar, Leo Mascarenhas, John A. Reeves, Marion Rudolph, Patricia Maeda, Barrett H. Childs, Theodore W. Laetsch, Alexander Drilon

https://www.abstractsonline.com/pp8/#!/9045/presentation/10962

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Last Updated on May 8, 2020 by Marie Benz MD FAAD