FDA Approves First Bispecific T-Cell Engager for Solid Tumors and Expands Indications for Immunotherapies
核心洞察
The FDA granted accelerated approval to tarlatamab (Imdelltra), the first bispecific T-cell engager for extensive-stage small cell lung cancer (搜索) (ES-SCLC) that has progressed after chemotherapy.
Nogapendekin alfa inbakicept-pmln (Anktiva), a first-in-class IL-15 receptor agonist, was approved in combination with Bacillus Calmette-Guérin (BCG) for non-muscle invasive bladder cancer (搜索) (NMIBC) unresponsive to BCG alone.
The FDA expanded the use of CAR T-cell therapies, approving lisocabtagene maraleucel (Breyanzi) for relapsed or refractory follicular lymphoma (搜索) and mantle cell lymphoma (搜索) after multiple lines of systemic therapy.
The U.S. Food and Drug Administration (FDA) has approved several new oncology therapies and expanded indications for existing treatments between April and June 2024, marking significant advancements in immunotherapy and targeted cancer care.
First Bispecific T-Cell Engager for Solid Cancer
Tarlatamab (Imdelltra) received accelerated approval for treating patients with extensive-stage small cell lung cancer (搜索) (ES-SCLC) that progressed during or after prior chemotherapy. ES-SCLC is an aggressive form of lung cancer with a high mortality rate. Tarlatamab is the first bispecific T-cell engager approved for a solid tumor, representing a significant milestone in cancer immunotherapy. It simultaneously binds to the delta-like ligand 3 (DLL3) protein on cancer cells and the CD3 protein on T cells, bringing them together to facilitate cancer cell killing. DLL3 is often expressed on the surface of cancer cells, making it an ideal target.
Bispecific T-cell Engagers Approved for Additional Patients with Blood Cancer
Blinatumomab (Blincyto) was approved as an early treatment for certain adult and pediatric patients with B-cell acute lymphoblastic leukemia (搜索) (B-ALL) as part of consolidation therapy. This approval expands the use of blinatumomab to patients whose B-ALL expresses CD19 but does not harbor the Philadelphia chromosome mutation, regardless of confirmed residual disease or relapse. Blinatumomab binds to CD3 on T cells and CD19 on leukemia cells.
Epcoritamab (Epkinly) received accelerated approval for adult patients with relapsed or refractory follicular lymphoma (搜索) who have received at least two prior lines of systemic therapy. Epcoritamab is the second bispecific T-cell engager approved for this patient population.
First-in-Class Therapeutics Make Their Debut
Nogapendekin alfa inbakicept-pmln (Anktiva), in combination with Bacillus Calmette-Guérin (BCG), was approved for certain patients with non-muscle invasive bladder cancer (搜索) (NMIBC) that has not responded to BCG alone. Nogapendekin alfa inbakicept-pmln activates the IL-15 receptor on immune cells, boosting their proliferation and activation to fight cancer. This is the first FDA approval for an IL-15 receptor agonist.
Imetelstat (Rytelo) was approved for certain myelodysplastic syndromes (搜索) (MDS) that are unresponsive to or ineligible for medications that stimulate blood cell production. Imetelstat inhibits telomerase, a protein that promotes cancer by elongating telomeres, allowing cancer cells to proliferate beyond normal limits. This is the first direct inhibitor of telomerase to receive FDA approval.
Antibody-Drug Conjugates Extend Their Reach
Fam-trastuzumab deruxtecan-nxki (Enhertu), also known as T-DXd, received a tissue-agnostic accelerated approval for patients with previously treated, unresectable or metastatic HER2 (搜索)-positive solid tumors. T-DXd targets cells expressing HER2, found at high levels in breast and gastric cancers, and less frequently in other tissues.
The accelerated approval of tisotumab vedotin-tftv (Tivdak) for recurrent or metastatic cervical cancer (搜索) after progression on prior chemotherapy was converted to a full approval. Tisotumab vedotin-tftv targets tissue factor, often highly expressed on cervical cancer cells.
New Indications for Additional Targeted Therapies
Selpercatinib (Retevmo) was approved for adults and children aged 2 years or older with certain advanced RET-mutated thyroid cancers (搜索). It also received accelerated approval for pediatric patients 2 years and older with certain locally advanced or metastatic RET-mutated solid tumors, regardless of origin. Selpercatinib inhibits mutant forms of the RET tyrosine kinase.
Tovorafenib (Ojemda) was approved for patients 6 months or older with relapsed or refractory low-grade glioma (搜索) (brain cancer) harboring certain BRAF (搜索) mutations. Tovorafenib inhibits RAF family kinases, including BRAF, and can cross the blood-brain barrier. This is the first systemic therapy approved for BRAF-mutated low-grade glioma in children.
Lutetium Lu 177 dotatate (Lutathera) was approved to treat children aged 12 or older with gastroenteropancreatic neuroendocrine tumors (搜索) (GEP-NETs) expressing the somatostatin receptor (SSTR). Lutetium Lu 177 dotatate targets SSTR, highly expressed on GEP-NET cells, and delivers radiation to kill the cells.
Repotrectinib (Augtyro) was approved for adult and pediatric patients aged 12 years or older with solid tumors that are locally advanced, metastatic, or ineligible for surgical removal; have progressed after prior treatment; and harbor NTRK gene fusions. Repotrectinib inhibits NTRK and other kinases and may be effective against tumors resistant to other NTRK inhibitors.
Alectinib (Alecensa) was approved for the postsurgical treatment of adults with non-small cell lung cancer (搜索) (NSCLC) that either overexpresses or has a mutation in the ALK (搜索) protein. Alectinib inhibits ALK activity.
Adagrasib (Krazati) in combination with cetuximab (Erbitux) received accelerated approval to treat KRASG12C (搜索)-mutated locally advanced or metastatic colorectal cancers (搜索) in adult patients who have received prior chemotherapy. Adagrasib inhibits the KRASG12C mutant protein, and cetuximab blocks epidermal growth factor receptor (EGFR) activity. The approval was based on the KRYSTAL-1 clinical trial results.
CAR T-cell Therapy for Additional B-cell Cancers
Lisocabtagene maraleucel (Breyanzi) received accelerated approval to treat patients with relapsed or refractory follicular lymphoma (搜索) who have already received at least two lines of systemic therapy. It was also approved for patients with relapsed or refractory mantle cell lymphoma (搜索) who previously received two or more lines of systemic therapy, including a Bruton’s tyrosine kinase inhibitor. Lisocabtagene maraleucel targets the CD19 protein on malignant B cells.
Immune Checkpoint Inhibitors for Endometrial Cancer
Durvalumab (Imfinzi) plus chemotherapy, followed by durvalumab alone, was approved for patients with advanced or recurrent endometrial cancers (搜索) that have defects in mismatch repair. Durvalumab binds the PD-L1 protein to prevent it from engaging with the PD-1 protein on T cells.