Tarlatamab Earns UK Approval for Previously Treated ES-SCLC

The United Kingdom’s (UK) Medicines and Healthcare products Regulatory Agency (MHRA) has granted conditional marketing authorization to the bispecific T-cell engager tarlatamab (Imdelltra) for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) who experienced disease progression on or after 2 or more prior lines of therapy, including platinum-based chemotherapy.1

Findings from the open-label, multicenter phase 2 DeLLphi-301 study (NCT05060016) supported this regulatory decision; data showed an objective response rate (ORR) of 41% (95% CI, 32%-52%) among patients treated with tarlatamab at a dose of 10 mg every 2 weeks (n = 99). The median duration of response (DOR) was 9.7 months (range, 5.9-not estimable).

“The MHRA’s granting of a conditional marketing authorization for tarlatamab is a significant step forward for people living with SCLC. More than 34,000 people die from lung cancer in the UK each year. There is a vital need for novel treatments, particularly for the extensive stage of small cell lung cancer, where outcomes are especially poor,” Tony Patrikios, executive medical director of Amgen UK & Ireland, stated in a news release. “This license brings us one step closer to offering a new treatment option to eligible patients.”

In May 2024, data from the primary analysis of DeLLphi-301 also supported the FDA approval of tarlatamab-dlle for the treatment of patients with ES-SCLC who progressed on or after platinum-based chemotherapy.2

DeLLphi-301 Overview

The open-label phase 2 trial evaluated tarlatamab in patients with previously treated SCLC who had an ECOG performance status of 0 or 1 and measurable disease.3 The presence of treated or stable brain metastases was also permitted.

In the dose-evaluation phase, 176 patients were randomly assigned 1:1 to receive tarlatamab at either 10 mg (n = 88) or 100 mg (n = 88). The 10-mg schedule involved 1 mg administered on day 1, followed by 10 mg on days 8 and 15, and then once every 2 weeks. The 100-mg group received 1 mg on day 1, followed by 100 mg on days 8 and 15, and then once every 2 weeks. In the dose-expansion phase, 12 patients received tarlatamab on the 10-mg schedule. In part 3, 34 patients were treated with the 10-mg schedule under a reduced inpatient monitoring protocol.

The study’s primary end point was ORR per RECIST 1.1 criteria as assessed by blinded independent central review (BICR). Key secondary end points included DOR, disease control rate, progression-free survival (PFS) per RECIST 1.1 by BICR, overall survival (OS), treatment-emergent adverse effects (AEs), and serum concentrations of tarlatamab. The data cutoff for efficacy end points excluding OS was January 12, 2024; the cutoff for OS was May 16, 2024.

Additional Efficacy and Safety Data

Additional long-term data from the DeLLphi-301 trial were presented at the 2024 IASLC World Conference on Lung Cancer. At a median follow-up of 16.6 months, 3% of patients treated with the 10-mg dose (n = 100) achieved a complete response, 37% achieved a partial response, 30% had stable disease, 20% experienced progressive disease, and 10% were not evaluable or lacked a post-baseline scan. Sustained disease control lasting at least 52 weeks was observed in 26% of patients with a median duration of disease control of 6.9 months (95% CI, 5.4-8.6). Tumor shrinkage occurred in 72% of patients. At the data cutoff, 43% of responses (n = 40) were ongoing, and the median time to response was 1.4 months (IQR, 1.3-1.4).

Moreover, the median PFS was 4.3 months (95% CI, 2.9-5.6), and the 6- and 12-month PFS rates were 39.2% and 24.0%, respectively. At a median follow-up of 20.7 months, the median OS was 15.2 months, and the Kaplan-Meier estimated 18-month OS rate was 46%. In the chemotherapy-free interval cohorts, OS rates at 6, 12, and 18 months were 73.4%, 57.0%, and 46.0%, respectively.

Regarding safety, the most common AEs reported with tarlatamab were cytokine release syndrome (53.8%), pyrexia (36.9%), dysgeusia (30.0%), decreased appetite (29.4%), constipation (27.5%), fatigue (26.9%), anemia (25.0%) and asthenia (21.9%).1 Additional AEs of note included nausea, hyponatremia, and dyspnea.

References

1. Amgen’s Imdylltra (tarlatamab) granted a conditional marketing authorisation for third-line treatment of extensive-stage small cell lung cancer in the United Kingdom. News Release. Amgen. January 6, 2024. Accessed January 6, 2025. https://www.biospace.com/press-releases/amgens-imdylltra-tarlatamab-granted-a-conditional-marketing-authorisation-for-third-line-treatment-of-extensive-stage-small-cell-lung-cancer-in-the-united-kingdom
2. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. FDA. May 16, 2024. Accessed January 6, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer
3. Sands J, Cho BC, Ann MJ, et al. Tarlatamab sustained clinical benefit and safety in previously treated SCLC: DeLLphi-301 phase 2 extended follow-up. J Thor Oncol. 2024;19(10):S30-S31.doi:10.1016/j.jtho.2024.09.057