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FDA Pipeline: Recent Designations in NSCLC, Leukemia, and Lymphoma


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Recently, the U.S. Food and Drug Administration (FDA) issued regulatory decisions related to treatments for non–small cell lung cancer (NSCLC), acute leukemia, and mantle cell lymphoma.

Breakthrough Therapy Designation for Adagrasib in Advanced NSCLC With KRAS G12C Mutation

On June 24, 2021, the FDA granted Breakthrough Therapy designation to adagrasib (MRTX849) for the potential treatment of patients with NSCLC who harbor the KRAS G12C mutation following prior systemic therapy.

Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRAS G12C that is optimized to sustain target inhibition. Studies of adagrasib have shown that the drug has a long half-life, extensive tissue distribution, and is well tolerated. Adagrasib has also shown single-agent responses in NSCLC, colorectal cancer, pancreatic cancer, and other solid tumors with KRAS G12C mutations. 

The designation for adagrasib is supported by preliminary results from the registrational phase I/II KRYSTAL-01 trial in patients with advanced NSCLC, whose cancer had progressed following prior treatment with immunotherapy and/or chemotherapy.

Fast Track Designation for SNDX-5613 for Relapsed/Refractory Acute Leukemias With Certain Mutations

On June 28, 2021, the FDA granted Fast Track designation to SNDX-5613 for the treatment of adult and pediatric patients with relapsed or refractory acute leukemias harboring a mixed lineage leukemia (MLL) rearranged or nucleophosmin (NPM1) mutation.

SNDX-5613 is a potent, selective, small-molecule inhibitor of the menin-MLL binding interaction that is being developed for the treatment of MLL rearranged acute leukemias including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and NPM1-mutant AML. In preclinical models of MLL rearranged acute leukemias, SNDX-5613 demonstrated robust, dose-dependent inhibition of tumor growth, resulting in a marked survival benefit.

The novel agent is currently being evaluated in the AUGMENT-101 phase I/II open-label clinical trial for the treatment of relapsed/refractory acute leukemias (ClinicalTrials.gov identifier NCT04065399). SNDX-5613 had previously been granted Orphan Drug designation by the FDA for the treatment of patients with AML. There are currently no approved therapies indicated for MLL rearranged leukemias or NPM1-mutant AML.

Breakthrough Therapy Designation for Orelabrutinib for Relapsed/Refractory Mantle Cell Lymphoma

Also on June 28, the FDA granted Breakthrough Therapy designation to the Bruton's tyrosine kinase (BTK) inhibitor orelabrutinib for the treatment of relapsed or refractory mantle cell lymphoma.

Orelabrutinib is a highly selective BTK inhibitor targeting both B-cell malignancy and autoimmune diseases. A phase II study of single-agent orelabrutinib in 106 Chinese patients with relapsed or refractory mantle cell lymphoma demonstrated an objective response rate of 87.9%, the primary endpoint, at a median follow-up of 16.4 months, and a favorable safety profile.

On December 25, 2020, orelabrutinib was approved by the China National Medical Products Administration in two indications: treatment of patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma and treatment of patients with relapsed/refractory mantle cell lymphoma.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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