The United Kingdom’s (UK) Medicines and Healthcare products Regulatory Agency (MHRA) has granted conditional marketing authorization to tarlatamab (Imdelltra) for the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) who have experienced disease progression on or after two or more prior lines of therapy, including platinum-based chemotherapy.
The decision is supported by findings from the open-label, multicenter phase 2 DeLLphi-301 study (NCT05060016). The data demonstrated 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).
Tony Patrikios, executive medical director of Amgen UK & Ireland, stated, “The MHRA’s granting of a conditional marketing authorization for tarlatamab is a significant step forward for people living with SCLC... This license brings us one step closer to offering a new treatment option to eligible patients.”
DeLLphi-301 Trial Details
The DeLLphi-301 trial evaluated tarlatamab in patients with previously treated SCLC who had an ECOG performance status of 0 or 1 and measurable disease. Patients with treated or stable brain metastases were also eligible. 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 primary endpoint of the study was ORR per RECIST 1.1 criteria as assessed by blinded independent central review (BICR). Key secondary endpoints 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 endpoints excluding OS was January 12, 2024; the cutoff for OS was May 16, 2024.
Efficacy and Safety Outcomes
Additional long-term data from the DeLLphi-301 trial presented at the 2024 IASLC World Conference on Lung Cancer showed that 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).
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.
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%). Additional AEs of note included nausea, hyponatremia, and dyspnea.
