Tarlatamab Shows Significant OS Improvement in Post-Platinum SCLC
Tarlatamab outperformed chemotherapy when used for the treatment of patients with small cell lung cancer in the phase 3 DeLLphi-304 trial.
Human lung illness model: © IDoPixBox - stock.adobe.com
Tarlatamab-dlle (Imdelltra) showed a statistically significant and clinically meaningful improvement in overall survival (OS) vs local standard-of-care (SOC) chemotherapy when used for the treatment of patients with small cell lung cancer (SCLC) who progressed on or after a single line of platinum-based chemotherapy, meeting the primary end point of the phase 3 DeLLphi-304 trial at a planned interim analysis.1
Tarlatamab’s safety profile in this study was consistent with its known profile. Full findings from the global, phase 3 DeLLphi-304 will be presented at an upcoming medical meeting.
"Small cell lung cancer is one of the most aggressive malignancies, with a high unmet need for more effective therapies. The topline results from DeLLphi-304 demonstrate overwhelming clinical benefit for people living with this devastating disease and affirm [tarlatamab] as standard of care," said Jay Bradner, MD, executive vice president, research and development, at Amgen, in a press release. "We look forward to sharing these results with the scientific community and health authorities as we continue our efforts to bring [tarlatamab] to patients worldwide."
DeLLphi-304, a global, randomized, open-label, phase 3 trial, is evaluating the efficacy and safety of tarlatamab when used for treating patients with SCLC who progressed on or after a single line of platinum-based chemotherapy. Enrollment was open to patients aged 18 years and older with histologically or cytologically confirmed SCLC with demonstrated progression or relapse. Patients were required to have progressed or recurred after 1 platinum-based regimen, have measurable disease, an ECOG performance status of 0 or 1, a minimum life expectancy of 12 weeks or longer, and adequate organ function.2
The study enrolled 509 patients. Once enrolled, patients were randomly assigned to receive either tarlatamab or local SOC chemotherapy, which consisted of topotecan in all countries except Japan; lurbinectedin in the US, Canada, Australia, Singapore, Korea; and amrubicin in Japan.1
OS serves as the primary end point of the trial, and secondary end points include progression-free survival (PFS), overall response, disease control, duration of response (DOR), quality-of-life, and safety.2
The estimated study completion date is July 31, 2027.
Beyond DeLLphi-304
In addition to DeLLphi-304, tarlatamab is currently under evaluation in the phase 2 DeLLphi-301 study (NCT05060016). Recent data has shown tarlatamab’s positive benefit-risk profile for the treatment of previously treated patients with SCLC, according to patient-reported outcomes from the phase 2 trial.3
Extended follow-up from the DeLLphi-301 study also demonstrated tarlatamab to lead to sustained anticancer activity and manageable safety in patients with extensive-stage SCLC (ES-SCLC) previously treated with platinum-based chemotherapy.4 Data presented at the 2024 World Conference on Lung Cancer specifically showed that at a median follow-up of 13.6 months (range, 0.1-20.9) for efficacy evaluation, the overall response rate was 40.4% and the median DOR was not estimable among those treated with the 10 mg dose. Responses were ongoing in 47.5% (n = 19) of responders and the median PFS was 4.3 months. Further, the median OS was 15.2 months, and the estimated OS rates at 6 and 12 months were 73.4% and 56.7%, respectively.
Additional clinical trials investigating tarlatamab include the phase 1b DeLLphi-303 study of tarlatamab in combination with SOC therapies in first-line ES-SCLC (NCT05361395); the phase 3 DeLLphi-305 trial of tarlatamab in combination with durvalumab vs durvalumab alone as first-line maintenance treatment in ES-SCLC (NCT06211036); the phase 3 DeLLphi-306 study of tarlatamab following concurrent chemoradiotherapy in limited-stage SCLC (NCT06117774); the phase 1b DeLLphi-308 study of subcutaneous tarlatamab in second line or later ES-SCLC (NCT06598306); and the phase 2 DeLLphi-309 trial of alternative intravenous dosing regimens with tarlatamab in second-line ES-SCLC (NCT06745323).
In May 2024, the FDA approved the bispecific T-cell engager (BiTE) tarlatamab for patients with SCLC that progressed on or after platinum-based chemotherapy, based on findings from the DeLLphi-301 study.5 This marked the first BiTE therapy to be approved for the treatment of a major solid tumor. Findings from the primary analysis of the trial were published in The New England Journal of Medicine and presented at the 2023 European Society of Medical Oncology Congress.
