Last Month in Oncology: FDA Cancer News Roundup
Last month, the US Food and Drug Administration (FDA) approved three new drugs, changed the indication for one, lifted a clinical trial hold, and began a probe into blood cancer risk from bluebird’s gene therapy, among other things. Here’s a snapshot of what happened in November. New drugs 1. The FDA has approved obecabtagene autoleucel
Last month, the US Food and Drug Administration (FDA) approved three new drugs, changed the indication for one, lifted a clinical trial hold, and began a probe into blood cancer risk from bluebird’s gene therapy, among other things.
Here’s a snapshot of what happened in November.
New drugs
1. The FDA has approved obecabtagene autoleucel, or obe-cel (AUTO1, Autolus Therapeutics), to treat relapsed or refractory adult B-cell acute lymphoblastic leukemia (ALL).
Approval of the CD19-targeted chimeric antigen receptor (CAR) T-cell therapy was based on efficacy and safety findings from the open-label, single-arm FELIX study. Among the 65 patients evaluable for efficacy, 27 patients (42%) achieved a complete response within 3 months, and the median duration of the complete response achieved within 3 months was 14.1 months.
The prescribing information includes a boxed warning for cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and T-cell malignancies. Cytokine release syndrome occurred in 75% of patients overall, 3% of which were grade 3, and neurologic toxicities occurred in 64% of patients, 12% of which were grade 3 or higher.
2. The FDA has approved revumenib (Revuforj, Syndax Pharmaceuticals) to treat relapsed or refractory acute leukemia with a KMT2A gene translocation in adult patients and pediatric patients aged 1 year or older. Approval for the oral small-molecule menin inhibitor was based on a single-arm open-label trial with 1src4 adult and pediatric patients with the mutation. The rate of complete remission plus complete remission with partial hematologic recovery was 21.2% and had a median duration of 6.4 months.
3. The FDA has approved zanidatamab (Ziihera, Jazz Pharmaceuticals, Inc) as monotherapy for previously treated, unresectable or metastatic HER2-positive biliary tract cancer, as detected by an FDA-approved test. This approval makes the bispecific antibody the first HER2-targeted treatment to carry the indication.
Approval was based on an open-label, single-arm study that found an objective response rate of 52% and a median duration of response of 14.9 months in the population of 62 patients. The prescribing information contains a boxed warning for embryo–fetal toxicity.
New Formulations
The FDA has approved a liquid formulation for imatinib (Imkeldi, Shorla Oncology) to treat leukemia and other cancers. The tyrosine kinase inhibitor was first approved in a tablet formulation under the brand name Gleevec (Novartis) in May 2srcsrc1. The new strawberry-flavored liquid formulation doesn’t require refrigeration and should help patients who have “difficulty swallowing or require dosing tailored to body surface area,” Shorla Oncology said in a press release. Imatinib carries indications for numerous cancer types, including Philadelphia chromosome–positive chronic myeloid leukemia and ALL as well as myelodysplastic syndrome/myeloproliferative disease and gastrointestinal tumors.
Changed Label
Drug labeling for fludarabine phosphate will be updated to reflect new and revised indications and dosage information. The new labeling — approved by the FDA under the Project Renewal initiative, which updates labeling for certain older oncology drugs — will note that fludarabine phosphate injection is approved as part of a treatment combination for adults with B-cell chronic lymphocytic leukemia (CLL) as well as for adults with B-cell CLL who don’t respond or whose disease progresses during treatment with at least one alkylating agent–containing regimen. The recommended dosage for use in combination with cyclophosphamide and rituximab will be included. And the boxed warning, citing a risk for central nervous system toxicity, hemolytic anemia, and pulmonary toxicity, will be removed and incorporated into the Warnings and Precautions section.
FDA Probe
The FDA is considering regulatory action on bluebird bio’s gene therapy Skysona (elivaldogene autotemcel, or eli-cel), as more reports of blood cancers have emerged in patients who received the therapy as part of clinical trials.
Skysona was approved in 2src22 for the treatment of cerebral adrenoleukodystrophy, a rare neurological disorder that typically occurs in boys aged 3-12 years. Prescribing information already includes a warning for blood cancers, but in a November 27 notice, the FDA said additional reports of hematologic malignancies prompted an evaluation of the need for further action. Alternative therapies should be considered, the agency noted.
Clinical Trial Holds
The FDA has lifted manufacturing facility–related clinical holds on trials for three autologous CAR T-cell products being developed by CARsgen Therapeutics Holdings Limited to treat hematologic malignancies and solid tumors. The CAR T-cell products are zevorcabtagene autoleucel (zevor-cel, CTsrc53), satricabtagene autoleucel (satri-cel, CTsrc41), and CTsrc71.
An inspection of the company’s Durham, North Carolina facility in December 2src23 led to the holds. At the time, the company promised a comprehensive review and resolution of manufacturing concerns.
Clinical Trial Setbacks
The phase 3 SKYSCRAPER-src1 study assessing tiragolumab (Genentech) plus atezolizumab (Tecentriq, Roche) vs atezolizumab alone to treat advanced or metastatic non–small cell lung cancer did not reach its primary endpoint of overall survival at the final analysis, Roche announced.
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