Lead Investigator: Alexander Drilon, Memorial Sloan Kettering Cancer Center (MSKCC)
Title of Proposal Research: Do patients with lung cancers positive for a RET gene alteration benefit from the addition of immunotherapy to chemotherapy?
Vivli Data Request: 10540
Funding Source: None
Potential Conflicts of Interest: The only direct COI is consulting/advisory Lilly/Loxo, all well below the the MSKCC Compliance cap and standard operating procedures, all will be declared in the publications/abstracts/presentations. No Lilly Funding. Dr. Alexia Iasonos reports: Stock and Other Ownership Interests – Bristol-Myers Squibb/Sanofi
Consulting or Advisory Role – Intelligencia; Mirati Therapeutics
Chapman and Hall – Intellectual Property Rights
Journal of Clinical Oncology – Professional Services and Activities (JCO deputy editor)
The COIs do not conflict with this project, but any conflicts that arise will be fully disclosed in subsequent publications or presentations.
Summary of the Proposed Research:
About 2 in 100 patients with lung cancer will have alterations for a gene called RET which makes an abnormal form of the RET protein. RET is a gene that makes a protein that plays an important role in cell growth and development in the body. Changes or alterations (also known as mutations or fusions) in the RET gene may cause the protein made by this gene to become overactive, which may cause abnormal cells, including cancer cells, to grow. These cancers are known as RET-positive (RET+) cancers.
Lung cancers can be treated with chemotherapy (which kills cancer cells by inhibiting their DNA and stopping cells from dividing and growing), RET targeted therapy (which directly targets the RET protein to decrease production of RET which helps fuel cancer growth), and immunotherapy (which helps the immune system to recognize and attack cancer cells). In patients with RET-positive lung cancer, chemotherapy has show activity, however, previous studies in small groups of patients have shown that immunotherapy by iteself does not work well in patients with the abnormal RET protein.
This project builds on that knowledge to ask the question: “Is immunotherapy helpful when added to chemotherapy for patients with RET+ cancers?”. This research is important as doctors do not yet know if it is beneficial to add immunotherapy to chemotherapy. This project will further analyze a phase 3 trial known as LIBRETTO-431. In this study, the activity of a RET targeted therapy was compared to the current standard of care (recommended treatment) in patients with RET+ lung cancer. There were two choices for the current standard of care, chemotherapy alone or chemotherapy with immunotherapy (chemoimmunotherapy). Our project will focus on the group of patients who received standard of care and compare the effectiveness to chemotherapy and to chemoimmunotherapy in the LIBRETTO-431 trial to see if there is a difference in how long treatment works and how much cancers shrink.
Requested Studies:
NCT04194944 (J2G-MC-JZJC, LIBRETTO-431)
Data Contributor: Lilly
Study ID: NCT04194944 (J2G-MC-JZJC, LIBRETTO-431)
Sponsor ID: NCT04194944 (J2G-MC-JZJC, LIBRETTO-431)