OncLive’s November Roundup of Key FDA Approvals in Oncology

FDA

Below is your guide to all therapeutic options greenlit by the FDA in November 2024. The recap consists of topline data supporting the approvals and features expert insights on what these decisions mean for clinical practice.

11/8: Obecabtagene Autoleucel in Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia

The regulatory agency approved obecabtagene autoleucel (Aucatzyl; obe-cel), a CD19-directed genetically modified autologous T-cell immunotherapy, for use in adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL) based on data from the phase 1/2 FELIX trial (NCT04404660). Of the 65 efficacy evaluable patients, 42% (95% CI, 29%-54%) achieved a complete remission (CR) within 3 months after infusion, and the median duration of CR was 14.1 months (95% CI, 6.1-not reached.

Michael R. Bishop, MD

Obe-cel features a distinct receptor compared with those in most other CAR T-cell therapies used in non-Hodgkin lymphoma and B-ALL, Michael R. Bishop, MD, professor of medicine and director of the Hematopoietic Stem Cell Transplantation Program, Hematology and Oncology (Cancer) Immunotherapy, at the University of Chicago Medicine, said in a past interview with OncLive®. Although this unique receptor targets the CD19 protein like other CAR T-cell therapies, it also exhibits a rapid on and off mechanism, mimicking the biological processes of physiological T-cell receptors, he added, explaining that this characteristic is believed to mitigate toxicity.

“This approval comes at a critical time and it’s a major milestone [for] patients with ALL,” Elias Jabbour, MD, said in another interview. “Splitting the dose allows us to deliver a safe CAR T-cell therapy [with] minimal complications and [it is] effective in the long run. [Obe-cel is also] an outpatient therapy, which will have a major impact on society and our patient’s lives. It’s a very important accomplishment that will fill a major unmet need.” Jabbour is a professor in the Department of Leukemia, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston.

In an episode of OncLive On Air, Paul J. Shaughnessy, MD, medical director of the Adult Blood and Marrow Stem Cell Transplant Program at Methodist Hospital in San Antonio, Texas, further discussed the significance of the obe-cel approval, highlighted key efficacy and safety findings from FELIX, and shed light on where the therapy fits into the treatment paradigm.

11/14: Nilotinib Tablets in Chronic Myeloid Leukemia

The FDA gave the green light to nilotinib (Danziten) tablets without mealtime restrictions for adult patients with newly diagnosed Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML) in chronic phase (CP), as well as adult patients with CP- and acute-phase CML that is resistant or intolerant to previous therapy that included imatinib (Gleevec).

The agent was initially approved with the trade name Tasigna in 2007 for use in the latter indication; it received approval for the former indication in 2010. With Tasigna, patients must avoid food for 2 hours before treatment and 1 hour after treatment, according to the prescribing information. If taken with food, the agent could result in significant prolonged QT interval. Data from the phase 3 ENESTnd (NCT00471497) and the phase 1/2 Study A2101 (NCT00109707) supported the respective approvals of Tasigna, and they are listed in the clinical trial evidence in the label for Danziten.

“Danziten offers a new nilotinib treatment option with the equivalent efficacy to Tasigna, but without the fasting requirements of Tasigna,” Richard Blackburn, chief executive officer of Azurity Pharmaceuticals, stated in a news release. “Unlike Tasigna, the boxed warning on the Danziten label has no requirement for patients to take their medication in a fasted state, liberating CML patients from mealtime restrictions.”

11/15: Revumenib in Relapsed/Refractory Acute Leukemia With KMT2A Translocation

The regulatory agency approved revumenib (Revuforj) for the treatment of adult and pediatric patients at least 1 year of age with relapsed or refractory acute leukemia and a KMT2A translocation based on findings from the phase 1/2 AUGMENT-101 trial (NCT04065399). In evaluable patients (n = 104), the menin inhibitor resulted in a CR plus CR with partial hematologic recovery (CRh; CR+CRh) rate of 21.2% (95% CI, 13.8%-30.3%) with a median duration of CR+CRh of 6.4 months (95% CI, 2.7-not estimable [NE]). In the those who achieved a CR or CRh with the agent (n = 22), the median time to response was 1.9 months (range, 0.9-5.6).

In a past interview with OncLive, Dan Pollyea, MD, MS, clinical director of Leukemia Services; Robert H. Allen Endowed Chair in Hematology Research; and associate professor of medicine in the Division of Hematology at the University of Colorado School of Medicine, explained the mechanism of action for revumenib in KMT2A-rearranged relapsed/refractory acute myeloid leukemia:

11/20: Zanidatamab in Previously Treated HER2+ Biliary Tract Cancer

The FDA awarded accelerated approval to zanidatamab-hrii (Ziihera) for use in adult patients with previously untreated, unresectable or metastatic HER2-positive (immunohistochemistry 3+) biliary tract cancer based on findings from the phase 2b HERIZON-BTC-01 trial (NCT04466891). In evaluable patients (n = 62), the agent elicited an objective response rate of 52% (95% CI, 39%-65%), including a complete response rate of 3.2% and a partial response rate of 48%. Among those who responded (n = 32), the median duration of response (DOR) was 14.9 months (95% CI, 7.4-NE); 59% had a DOR of at least 6 months and 44% experienced a DOR of at least 44%.

In a recent interview, James J. Harding, MD, associate attending physician at Memorial Sloan Kettering Cancer Center in New York, discusses the significance of the approval in this population:

Subsequently, the regulatory agency approved the PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Antibody test for use as a companion diagnostic to assess HER2-positive status in patients with biliary tract cancer who may be candidates to receive zanidatamab.

11/25: Oral Solution of Imatinib in Select Leukemias, Other Cancers

The FDA gave the green light to an oral solution of imatinib (Imkeldi) for use in the following indications: adult and pediatric patients with newly diagnosed Ph-positive CP-CML; those with Ph-positive CML in blast crisis, accelerated phrase, or chronic phase following failure of interferon-alpha therapy; adult patients with relapsed or refractory Ph-positive ALL plus chemotherapy; adult patients with myelodysplastic or myeloproliferative diseases linked with PDGFR gene rearrangements; adult patients with aggressive systemic mastocytosis without c-KIT D816V mutations or with unknown c-KIT mutational status; adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) with the FIP1L1-PDGFRα fusion kinase and those with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or have unknown status; adult patients with unresectable, recurrent, and/or metastatic dermatofibrosarcoma protuberans; patients with KIT CD117-positive unresectable and/or metastatic malignant gastrointestinal stromal tumor (GIST); and as adjuvant treatment in adult patients following resection of KIT CD117-positive GIST.

Sharon Cunningham

“We are thrilled to offer an oral solution option for patients with leukemia and other cancers, a meaningful advancement for thousands in need,” Sharon Cunningham, chief executive officer of Shorla, stated in a news release. “Oral solutions may ensure more precise and consistent dosing, offering a convenient alternative to compounding for patients who have difficulty swallowing or require dosing tailored to body surface area.”

Other Noteworthy Decisions:

• Under Project Renewal, the regulatory agency approved updated drug labeling for fludarabine phosphate. The injection is now approved as a component of a regimen for use in adult patients with B-cell chronic lymphocytic leukemia (CLL) and for adults with B-cell CLL who have not responded to or whose disease has progressed during treatment with at least 1 alkylating agent–containing regimen.
• The FoundationOne Liquid CDx was approved for use as a companion diagnostic to identify patients with metastatic non–small cell lung cancer and MET exon 14 skipping alterations who could be eligible to receive tepotinib (Tepmetko), which received full approval in February 2024.

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