The alkylating agent lurbinectedin (Zepzelca – Jazz) has received accelerated approval from the FDA for treatment of metastatic small-cell lung cancer (SCLC) in adults with disease progression on or after platinum-based chemotherapy. Accelerated approval was based on the overall response rate and duration of response. About 13-15% of lung cancers are small-cell cancers. Most SCLCs occur in patients who are current or former smokers.

Tarlatamab-dlle (Imdelltra – Amgen), a first-in-class bispecific delta-like ligand 3 (DLL3)-directed CD3 T-cell engager, has received accelerated approval from the FDA for treatment of extensive-stage small cell lung cancer (SCLC) in adults who had disease progression on or after platinum-based chemotherapy. It is the first bispecific DLL3-directed CD3 T-cell engager to be approved in the US for this indication. Most patients with SCLC have a response to initial treatment, but progression generally occurs within a few months and overall survival is usually less than 8 months....

Mobocertinib (Exkivity – Takeda), an oral kinase inhibitor, has received accelerated approval from the FDA for treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations in adults whose disease has progressed on or after platinum-based chemotherapy. Accelerated approval was based on the overall response rate and duration of response. Mobocertinib is the second drug to become available in the US for this indication; the IV EGFR-MET bispecific antibody amivantamab (Rybrevant) was approved...

Amivantamab-vmjw (Rybrevant – Janssen), an EGFR-MET bispecific antibody, has received accelerated approval from the FDA for IV treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations in adults whose disease has progressed on or after platinum-based chemotherapy. It is the first bispecific antibody to become available in the US for this indication. Accelerated approval of the drug was based on the overall response rate and duration of response.

The FDA has approved ensartinib (Ensacove – Xcovery), an oral kinase inhibitor, for treatment of anaplastic lymphoma kinase (ALK)-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) in adults who have not previously received an ALK inhibitor (e.g, crizotinib [Xalkori], certinib [Zykadia], alectinib [Alecensa], brigatinib [Alunbrig], lorlatinib [Lorbrena]). All previously approved ALK inhibitors are also approved for first-line use.

The FDA has approved the oral tyrosine kinase inhibitor repotrectinib (Augtyro – BMS) for treatment of locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) in adults. Repotrectinib is the third oral tyrosine kinase inhibitor to be approved for this indication in the US; crizotinib (Xalkori) and entrectinib (Rozlytrek) were approved earlier.

Lazertinib (Lazcluze – Janssen Biotech), an oral kinase inhibitor, has been approved by the FDA for use in combination with the EGFR-MET bispecific antibody amivantamab (Rybrevant) for first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in adults with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations. This is the first approval for Lazcluze; amivantamab was previously approved for use alone and in combination with carboplatin and pemetrexed for treatment of NSCLC with EGFR exon 20 insertion...

The oral kinase inhibitor osimertinib (Tagrisso – AstraZeneca), which has been available for years for treatment of non-small cell lung cancer (NSCLC) in adults with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, has now been approved for treatment of unresectable stage III EGFR-mutated NSCLC. About 20-30% of patients with NSCLC have locally advanced stage III NSCLC, and 60-90% of these patients have unresectable disease. Osimertinib is the first targeted therapy to be approved for the new indication.

The FDA has granted regular approval to the oral kinase inhibitor tepotinib (Tepmetko – EMD Serono) for treatment of adults with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations. MET exon 14 skipping mutations occur in 3-4% of NSCLC cases and are associated with advanced disease and a poor prognosis. Tepotinib received accelerated approval for the same indication in 2021 based on initial overall response rates and duration of response.

Atezolizumab (Tecentriq – Genentech), an immune checkpoint inhibitor, has been approved by the FDA for treatment of unresectable or metastatic alveolar soft part sarcoma (ASPS) in patients ≥2 years old. It was previously approved for treatment of non-small cell lung cancer, small cell lung cancer, hepatocellular cancer, and melanoma (see Table 1). Atezolizumab is the first drug to be approved in the US for treatment of ASPS. ASPS is a rare disorder that affects mostly adolescents and young adults; <1% of soft tissue sarcomas are ASPS.