FDA Grants Priority Review to Tarlatamab for Small Cell Lung Cancer

The FDA has accepted and granted priority review to the biologics license application (BLA) seeking the approval of tarlatamab for the treatment of patients with advanced small cell lung cancer (SCLC).¹

The designation is based on findings from the phase 2 DeLLphi-301 trial (NCT05060016), which were presented at the 2023 ESMO Congress and simultaneously published in the New England Journal of Medicine.^2,3 Results showed that tarlatamab led to a median progression-free survival (PFS) of 4.9 months (95% CI, 2.9-6.7) in the 10-mg cohort and 3.9 months (95% CI, 2.6-4.4) in the 100-mg cohort of patients with advanced SCLC and disease progression on or after platinum-based chemotherapy. Median overall survival (OS), though not yet mature with over 50% of patients in both cohorts still alive at last follow-up, was 14.3 months (95% CI, 10.8-not evaluable [NE]) and NE (95% CI, 12.4-NE) in the 10-mg and 100-mg cohorts, respectively.

The target action date is June 12, 2024, under the Prescription Drug User Fee Act.¹

“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, stated in a news 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 is a potential first-in-class, investigational DLL3-targeting bispecific T-cell engager (BiTE) designed for the treatment of adult patients with advanced SCLC with disease progression on or after platinum-based chemotherapy.

In October 2023, the FDA granted breakthrough therapy designation to tarlatamab.

The DeLLphi-301 trial enrolled patients with extensive-stage SCLC who had received at least 2 lines of prior therapy, including platinum-doublet chemotherapy. An ECOG performance status of 2 or less and measurable disease was also required. Patients with treated and stable brain metastases were allowed to enroll.²

In part 1, patients were randomly assigned 1:1 to received 10 mg (n = 88) or 100 mg (n = 88) of tarlatamab. In both arms, patients received 1 mg of the agent on day 1, followed by their assigned dose on days 8, 15, and every 2 weeks thereafter. In parts 2 (n = 12) and 3 (n = 34), the dose-expansion and reduced inpatient monitoring periods, respectively, patients received 10 mg of tarlatamab in the same dosing schedule as in part 1.

The primary end point was objective response rate (ORR) per RECIST v1.1 criteria by blinded independent central review (BICR), treatment-emergent adverse effects, and serum concentrations of tarlatamab. Secondary end points included duration of response (DOR), disease control rate (DCR), PFS per RECIST v1.1 criteria by BICR, and OS.

Additional results showed that in the 10-mg arm (n = 100), the ORR was 40% (97.5% CI, 29%-52%), with a DCR of 70% (95% CI, 60%-79%). In the 100-mg arm (n = 88), the ORR was 32% (97.5% CI, 21%-44%), with a DCR of 63% (95% CI, 52%-73%). Notably, responses were recorded irrespective of DLL3 expression or availability of tumor tissue.

The median time to response was 1.4 months (range, 1.1-9.6), and the median DOR was not reached. Of the 68 responders, 59% (n = 40) remained in response for 6 months or more.

Regarding safety, the adverse effect (AE) profile of tarlatamab in DeLLphi-301 was consistent with that from the phase 1 DeLLphi-300 trial (NCT03319940).^1,4 In both DeLLphi-300 and DeLLphi-301, the most common treatment-related AEs were cytokine release syndrome (52% to 55%), pyrexia (31% to 37%), and dysgeusia (22% to 26%), which were primarily grade 1/2. AEs leading to treatment discontinuation occurred in 3% to 4% of patients in both trials.

Tarlatamab, 10 mg every 2 weeks is currently under investigation in the phase 3 DeLLphi-304 trial (NCT05740566) vs standard chemotherapy in patients with relapsed SCLC following treatment with 1 line of platinum-based chemotherapy.²

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://www.amgen.com/newsroom/press-releases/2023/12/fda-grants-priority-review-to-amgens-tarlatamab-application-for-advanced-small-cell-lung-cancer
2. Paz-Ares L, Ahn MJ, 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. Ann Oncol. 2023;34(suppl 2):S1333-S1334. doi:10.1016/j.annonc.2023.10.094
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
4. Paz-Ares L, Champiat S, Lai WV, et al. Tarlatamab, a first-in-class DLL3-targeted bispecific T-cell engager, in recurrent small-cell lung cancer: an open-label, phase I study. J Clin Oncol. 2023;41(suppl 16):2893-2903. doi:10.1200/JCO.22.02823