Tarlatamab Earns FDA Priority Review in Advanced Small Cell Lung Cancer

Supporting data for the BLA came from the phase 2 DeLLphi-301 trial (NCT05060016), which investigators presented at the 2023 European Society for Medical Oncology (ESMO) Congress and subsequently published in The New England Journal of Medicine.

The FDA has granted priority review to a biologics license application (BLA) for tarlatamab as a treatment for those with advanced small cell lung cancer (SCLC) who have progressed during or following platinum-containing chemotherapy, according to a press release from Amgen.¹

The regulatory agency has set a Prescription Drug User Fee Act date of June 12, 2024, for their its decision on approving tarlatamab in the aforementioned population.

Supporting data for the BLA came from the phase 2 DeLLphi-301 trial (NCT05060016), which investigators presented at the 2023 European Society for Medical Oncology (ESMO) Congress² and subsequently published in The New England Journal of Medicine.³

Findings from the DeLLphi-301 trial highlighted an objective response rate (ORR) of 40.0% (97.5% CI, 29.1%-51.7%) in patients treated with tarlatamab at the 10 mg dose level (n = 100) as well as an ORR of 31.8% (97.5% CI, 21.1%-44.1%) in those who received the 100 mg dose (n = 88).² In each respective dose cohort, the median overall survival (OS) was 14.3 months (95% CI, 10.8-not evaluable [NE]) and NE (95% CI, 12.4-NE), and the median progression-free survival (PFS) was 4.9 months (95% CI, 2.9-6.7) and 3.9 months (95% CI, 2.6-4.4). The median duration of response (DOR) was NE in the 10 mg (95% CI, 5.9-NE) and the 100 mg (95% CI, 6.6-NE) dose groups.

The most frequent treatment-emergent adverse effect (TEAE) in the 10 mg and 100 mg cohorts, respectively, was cytokine release syndrome (51.1% vs 60.9%). Treatment discontinuation following treatment-related AEs were reported in 3.0% and 3.4% of patients in each respective dose cohort.

“The FDA's priority review designation for this application underscores the urgency to provide new treatment options for patients with advanced SCLC who have progressed following treatment with platinum-based chemotherapy,” David M. Reese, MD, executive vice president of Research and Development at Amgen, said in the press release.¹ “…For patients who relapse, there are limited treatment options, emphasizing the importance of bringing new therapies to this patient population with advanced disease.”

In the DeLLphi-301 trial, patients with SCLC were randomly assigned to receive 10 mg or 100 mg of tarlatamab intravenously every 2 weeks.

The trial’s primary end point was ORR as assessed by blinded independent central review. Secondary end points included DOR, PFS, OS, and TEAEs.

Patients 18 years and older with histologically or cytologically confirmed relapsed/refractory SCLC that has progressed after 1 platinum-based combination and 1 or more other lines of therapy were able to enroll on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks or more weeks, and measurable lesions based on RECIST v1.1 criteria.

Those with untreated or symptomatic brain metastases and leptomeningeal disease or interstitial lung disease were not able to enroll on the trial. Patients were also unsuitable for enrollment if they had unresolved toxicity following a prior line of anti-cancer therapy.

References

1. FDA grants priority review to Amgen's tarlatamab application for advanced small cell lung cancer. News release. Amgen. December 13, 2023. Accessed December 14, 2023. https://prn.to/47X7yu7
2. Paz-Ares L, Ahn M, Felip E, et al. Tarlatamab for patients (pts) with previously treated small cell lung cancer (SCLC): Primary analysis of the phase II DeLLphi-301 study. Presented at: European Society for Medical Oncology Congress 2023; October 20-24, 2023; Madrid, Spain. Abstract LBA92.
3. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for patients with previously treated small-cell lung cancer. N Engl J Med. 2023;389:2063-2075. doi:10.1056/NEJMoa2307980