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FDA Pipeline: Designations and Applications Granted in Lymphoma, Small Cell Lung Cancer, Multiple Myeloma, and More

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Recently, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to a phospholipid-drug conjugate in diffuse large B-cell lymphoma; granted Orphan Drug designation to an immunotherapy for small cell lung cancer (SCLC); accepted supplemental biologics license applications (sBLAs) in multiple myeloma, melanoma, and several other solid tumors/hematologic malignancies; and approved a companion diagnostic.

Fast Track Designation for CLR 131 in Diffuse Large B-Cell Lymphoma

The FDA has granted Fast Track designation for CLR 131 in relapsed or refractory diffuse large B-cell lymphoma (DLBCL). CLR 131 is a small-molecule, cancer-targeting radiotherapeutic phospholipid-drug conjugate designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. It is currently being evaluated in the ongoing phase II CLOVER-1 clinical study in patients with relapsed or refractory select B-Cell lymphomas.

CLOVER-1 is being conducted in approximately 10 centers in the United States in patients with relapsed or refractory B-cell hematologic cancers. The malignancies being studied in the trial include multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, mantle cell lymphoma, and DLBCL.

The study will enroll up to 80 patients. Its primary endpoint is clinical benefit response, with additional endpoints of overall response rate, progression-free survival, median overall survival, and other markers of efficacy following a fractionated dose of 37.5 mCi/m2 of CLR 131 administered in two 30-minute infusions of 18.75 mCi/m2 of CLR 131 on day 1 and day 8, with the option for a second dose cycle approximately 75 to 180 days later. Topline data are expected later in 2019.

CLR 131 was granted Orphan Drug designation for the treatment of multiple myeloma and was granted Orphan Drug and Rare Pediatric Disease designations for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma, and osteosarcoma.

Orphan Drug Designation for Durvalumab in SCLC

The FDA has granted Orphan Drug designation to durvalumab for the treatment of SCLC. Durvalumab is a monoclonal antibody that binds to programmed cell death ligand 1 (PD-L1) and blocks the interaction of PD-L1 with programmed cell death protein 1 (PD-1) and CD80, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.

In June 2019, the phase III CASPIAN trial met its primary endpoint with durvalumab by showing a statistically significant and clinically meaningful improvement in overall survival for patients with extensive-stage SCLC. These patients were treated with durvalumab in combination with standard-of-care etoposide and platinum-based chemotherapy vs chemotherapy alone. Results will be shared at a forthcoming medical meeting. 

Durvalumab is currently approved for unresectable, stage III non–small cell lung cancer after chemotherapy and radiation therapy.

Isatuximab sBLA Accepted for Relapsed or Refractory Multiple Myeloma

The FDA has accepted and will review an sBLA for isatuximab for the treatment of patients with relapsed or refractory multiple myeloma. The target action date for the FDA decision is April 30, 2020. Isatuximab is an investigational monoclonal antibody that targets a specific epitope on the CD38 receptor of plasma cells. 

The sBLA is based on positive results from ICARIA-MM, an open-label, pivotal phase III clinical trial of isatuximab in patients with relapsed or refractory multiple myeloma. ICARIA-MM is the first positive randomized phase III trial to evaluate an antibody in combination with pomalidomide and dexamethasone. Results from this trial were presented at the 2019 ASCO Annual Meeting and the 2019 European Society of Hematology Annual Meeting.  

FDA Accepts sBLAs for Pembrolizumab 6-Week Dosing Schedule for Melanoma and Multiple Other Indications

The FDA has accepted for review six sBLAs to update the dosing frequency for pembrolizumab, a programmed cell death protein 1 inhibitor, to include an every-6-week dosing schedule option. The sBLA is seeking FDA approval of a 400 mg every-6-week dose infused over 30 minutes for pembrolizumab indications in melanoma, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, gastric cancer, hepatocellular carcinoma, and Merkel cell carcinoma. 

If approved by the FDA, the every-6-week dose would be available for use in adults in addition to the currently approved dose of pembrolizumab at 200 mg every 3 weeks infused over 30 minutes. The FDA has set a target action date of February 18, 2020.

Expanded Indication for FoundationOne CDx as a Companion Diagnostic for Olaparib

The FDA approved FoundationOne CDx to be used as a companion diagnostic for olaparib for first-line maintenance therapy in BRCA-mutated advanced ovarian cancer. FoundationOne CDx is an FDA-approved comprehensive genomic-profiling test for all solid tumors that incorporates multiple companion diagnostics. FoundationOne CDx detects BRCA1 and BRCA2 mutations, including both germline and somatic mutations.

In December of 2018, the FDA approved olaparib for use as maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy.

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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