Tarlatamab is better than chemotherapy in second-line SCLC

Phase 3 data showed survival and symptom benefits with a delta-like ligand 3 (DLL3)-targeted bispecific T-cell engager tarlatamab in relapsed small-cell lung cancer (SCLC).

Having demonstrated promising activity in phase 1/2 trials (DeLLphi-300: NCT03319940, DeLLphi-301: NCT05060016) for participants with relapsed SCLC, tarlatamab moved into phase 3 in the multinational phase 3 DeLLphi-304 trial (NCT05740566). Prof. Charles Rudin (Memorial Sloan Kettering Cancer Center, NY, USA) presented the promising interim results, which were simultaneously published in the New England Journal of Medicine [1,2]. The open-label trial enrolled 509 participants whose disease had progressed during or after first-line platinum-based chemotherapy. Participants were randomised to receive either tarlatamab or the physician’s choice of chemotherapy (topotecan, lurbinectedin, or amrubicin).

Tarlatamab significantly prolonged overall survival (OS) compared with chemotherapy, with a median OS of 13.6 months versus 8.3 months (HR 0.60; 95% CI 0.47–0.77; P<0.001). “This is the first phase 3 study to show a survival benefit with an immunotherapy in second-line SCLC,” Prof. Rudin highlighted. “The magnitude of benefit and safety profile positions tarlatamab as a potential new standard of care in this setting.”

Also, the progression-free survival and participant-reported symptom relief favoured tarlatamab. Grade ≥3 adverse events were less frequent with tarlatamab (54%) than with chemotherapy (80%), and fewer participants discontinued treatment due to toxicity (5% vs 12%). “Taking the efficacy and safety data together, these data clearly support tarlatamab as a preferable therapy for patients in the second-line setting for SCLC,” Prof. Rudin concluded. “Beyond redefining the standard-of-care for these patients, this study also establishes a new paradigm for the use of bispecific, T-cell engager immunotherapies for our patients with lung cancer.”

1. Rudin C, et al. Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): primary analysis of Ph3 DeLLphi-304. Abstract LBA8008, ASCO Annual Meeting 2025, 30 May–3 June, Chicago, IL, USA.
2. Mountzios G, et al. N Engl J Med. 2025 Jun 2. DOI: 10.1056/NEJMoa2502099.

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Posted on 30 July 2025