FDA Grants Priority Review to Tarlatamab in Advanced SCLC


The FDA has granted priority review approval to tarlatamab for advanced small cell lung cancer based on encouraging results in a phase 2 clinical trial.

  • Encouraging results from DeLLphi-301 trial (NCT05060016) demonstrated antitumor activity, durable response, and promising survival outcomes in patients with previously treated small cell lung cancer (SCLC) when given tarlatamab (AMG 757), supporting the priority review approval of tarlatamab.
  • A Prescription Drug User Fee Act (PDUFA) target action date was set for June 12, 2024, based on this designation.
  • With this FDA acceptance, there is potential for a quicker approval process, highlighting the urgency and unmet need for new treatment options in advanced SCLC.

FDA logo

The FDA has granted priority review approval for the biologics license application (BLA) for tarlatamab for patients with advanced small cell lung cancer with disease progression on or after platinum-based chemotherapy.1

The basis of this BLA comes from results from the phase 2 DeLLphi-301 trial which showed among patients with previously treated SCLC given tarlatamab, antitumor activity was observed along with a durable response and encouraging survival outcomes. The safety profile observed in the phase 2 study was in line with findings reported from a phase 1 trial.

Based on these data, a PDUFA date for tarlatamab has been set for June 12, 2024.

"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," said David M. Reese, MD, executive vice president of research and development at Amgen, in a press release. "While first-line treatments often show strong responses, patients can experience aggressive recurrences and long-term survival remains a challenge. Unfortunately, for patients who relapse, there are limited treatment options, emphasizing the importance of bringing new therapies to this patient population with advanced disease."

Tarlatamab, a potential first-in-class, investigational delta-like ligand 3 (DLL3) targeting agent is a bispecific T-cell engager (BiTE) therapy developed for adult patients with advanced SCLC with disease progression on or after platinum-based chemotherapy. A breakthrough therapy designation was previously granted to the agent by the FDA in October, and the application is being reviewed by the FDA under the Project Orbis framework and real-time oncology review.

Image of small cell lung cancer cells - stock.adobe.com

Image of small cell lung cancer cells - stock.adobe.com

About the DeLLphi-301 Trial of Tarlatamab in SCLC

The DeLLphi-301 trial is a phase 2 study where investigators evaluated the antitumor activity and safety of tarlatamab when given every 2 weeks via intravenous infusion at a dose of 10 mg or 100 mg, in patients with previously treated SCLC.2

The primary end point was objective response as assessed by blinded independent central review according to the RECIST v1.1.

According to findings, 220 patients received tarlatamab and in the study, the median prior lines of therapy received among patients was 2.3 In the 10 mg group of patients evaluated for antitumor activity and survival, the median follow-up was 10.6 months and in the 100-mg group, the median follow-up was 10.3 months. In the 10-mg vs 100-mg groups, an objective response occurred in 40% (97.5% CI, 29%-52%) of the patients vs 32% (97.5% CI, 21%-44%) of patients. Of the patients with an objective response, the duration of response was at least 6 months in 40 of the 68 patients (59%), and at the time of the data cutoff, objective responses were ongoing in 22 of 40 patients (55%) in the 10-mg group vs 16 of 28 patients (57%) in the 100-mg group.

Further, the median progression-free survival was 4.9 months (95% CI, 2.9-6.7) among patients treated at the 10-mg dose vs 3.9 months (95% CI, 2.6-4.4) at the 100-mg dose, and the overall survival estimates at 9 months were 68% vs 66% of patients, respectively.

For safety in the 10-mg vs 100-mg groups, cytokine-release syndrome (CRS; 51% vs 61%), decreased appetite (29% vs 44%), and pyrexia (35% vs 33%) were the most commonly observed adverse events (AEs). CRS was primarily observed within cycle 1 of treatment. Most AEs were grade 1 or 2 in severity.3

In addition to the DeLLphi-301 trial, a phase 1b study titled DeLLphi-302 is evaluating tarlatamab in combination with an anti-PD-1 therapy in second-line or later SCLC, the phase 1b DeLLphi-303 trial is assessing tarlatamab combined with standard of care therapies in first-line SCLC, the phase 3 DeLLphi-304 trial is comparing tarlatamab monotherapy with standard of care chemotherapy in second-line treatment of SCLC and currently enrolling patients, the phase 3 DeLLphi-306 is evaluating tarlatamab following chemoradiotherapy in earlier settings of SCLC, and the phase 1b DeLLpro-300 study is assessing tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer. Additionally, there are plans to initiate an additional phase 3 study of tarlatamab in first-line treatment of SCLC.

1. FDA grants priority review to Amgen's tarlatamab application for advanced small cell lung cancer. News release. Amgen. December 13, 2023. Accessed December 13, 2023. http://tinyurl.com/mr3afdya
2. A phase 2 study of tarlatamab in patients with small cell lung cancer (SCLC) (DeLLphi-301). ClinicalTrials.gov. Updated October 18, 2023. Accessed December 13, 2023. https://www.clinicaltrials.gov/study/NCT05060016
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(22):2063-2075. doi:10.1056/NEJMoa2307980
Related Videos
Related Content