Sevabertinib Receives Accelerated FDA Approval
The US Food and Drug Administration (FDA) has granted accelerated approval to sevabertinib as a treatment for locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain (TKD) activating mutations. The approval, announced on November 19, applies to patients who have already received systemic therapy and whose tumors test positive using an FDA-approved diagnostic test.
The decision is supported by data from the SOHO-01 trial, an open-label, single-arm, multicenter, multi-cohort clinical trial, which showed clinically meaningful response rates in patients with and without prior HER2-directed antibody-drug conjugate (ADC) treatment.1
In the cohort of 70 patients who had received prior systemic therapy but had not been exposed to HER2-targeted ADCs, sevabertinib yielded an objective response rate (ORR) of 71% (95% CI: 59, 82). The median duration of response (DOR) was 9.2 months (95% CI: 6.3, 15), and 54% of responders maintained their response for at least 6 months.1
In a separate cohort of 52 patients whose previous treatment included a HER2-directed antibody drug conjugate, the ORR was 38% (95% CI: 25, 53). The median DOR reached 7 months (95% CI: 5.6, not evaluable), with 60% of patients experiencing a response lasting 6 months or longer.1
Tarlatamab-dlle is FDA-Approved for ES-SCLC
On November 19, the FDA granted traditional approval to tarlatamab-dlle for extensive-stage small cell lung cancer (ES-SCLC) whose disease progressed on or after platinum-based chemotherapy, with or without an anti-PD-(L)1 antibody. The FDA’s action reflects data from DeLLphi-304, a multicenter, randomized, open-label study.2
In the trial, 509 patients were randomly assigned in a 1:1 ratio to receive either tarlatamab-dlle or standard-of-care (SOC) chemotherapy (topotecan, lurbinectedin, or amrubicin) until disease progression or unacceptable toxicity. Overall survival (OS) served as the primary endpoint, with progression-free survival (PFS) and patient-reported outcomes included as secondary measures.2
Tarlatamab-dlle demonstrated a median OS of 13.6 months (95% CI: 11.1, not evaluable) compared with 8.3 months (95% CI: 7, 10.2) in the SOC arm (hazard ratio [HR] 0.60 [95% CI: 0.47, 0.77]; p value < 0.001). Median PFS was 4.2 months (95% CI: 3.0, 4.4) and 3.2 months (95% CI: 2.9, 4.2) in the respective arms (HR 0.72 [95% CI: 0.59, 0.88]; p value < 0.001).2> The trial also demonstrated a statistically significant improvement in dyspnea at week 18 for patients who were randomly assigned to tarlatamab-dlle compared to SOC.2
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