The UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted conditional marketing authorization to Amgen's Imdylltra (tarlatamab) for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has progressed following at least two prior lines of therapy, including platinum-based chemotherapy. This decision marks a significant advancement in the treatment landscape for this aggressive cancer. The approval was granted on December 31, 2024.
Clinical Efficacy and Safety
The MHRA's decision was primarily based on the results of the Phase 2 DeLLphi-301 trial (NCT05060016), an open-label, multicenter study that evaluated tarlatamab in patients with ES-SCLC who had failed two or more prior lines of treatment. The study demonstrated an objective response rate (ORR) of 41% (95% Confidence Interval [CI]: 32 to 52) and a median duration of response (DoR) of 9.7 months (range: 5.9, not estimable [NE]) with the 10 mg every two weeks (Q2W) dose (N=99).
Tony Patrikios, Executive Medical Director, Amgen UK & Ireland, stated, "The MHRA’s granting of a conditional marketing authorisation for tarlatamab is a significant step forward for people living with small cell lung cancer... There is a vital need for novel treatments, particularly for the extensive stage of small cell lung cancer, where outcomes are especially poor."
Mechanism of Action
Tarlatamab is a bispecific T-cell engager (BiTE) designed to target the delta-like ligand 3 (DLL3) protein, which is expressed on the surface of tumor cells. By simultaneously binding to DLL3 on tumor cells and CD3 on T cells, tarlatamab triggers T-cell activation, leading to the release of inflammatory cytokines and cytotoxic proteins, ultimately resulting in the lysis of tumor cells. This mechanism harnesses the body's own immune system to fight cancer.
Disease Burden and Unmet Need
Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases and is characterized by rapid tumor growth and early metastasis. ES-SCLC, in particular, has a poor prognosis, with a median survival of approximately 9-12 months. While initial responses to platinum-based chemotherapy are often high, most patients relapse within months, highlighting the urgent need for more effective treatment options. Current second-line treatments offer limited survival benefits, and third-line options are scarce.
Regulatory Context and Future Outlook
The MHRA's conditional marketing authorization signifies that further evidence on tarlatamab is awaited. The decision was made under Project Orbis, a collaborative program among international regulatory bodies aimed at accelerating the approval of promising cancer treatments. The U.S. Food and Drug Administration (FDA) had previously approved tarlatamab (marketed as Imdelltra in the US) in May 2024 for ES-SCLC.
While Imdylltra has demonstrated promising efficacy, it is associated with side effects, including cytokine release syndrome (CRS) and neurologic toxicity. Healthcare professionals are advised to closely monitor patients for adverse reactions and report any suspected side effects to the MHRA Yellow Card scheme.
With this approval, Imdylltra is projected to generate $217 million this year and is expected to achieve blockbuster status by 2029, according to GlobalData’s Pharma Intelligence Centre.
