The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.

Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.

The research was presented at the European Lung Cancer Congress 2024 on March 22.

Tarlatamab targets cancer cells that express the delta-like ligand 3 (DLL3), which occurs infrequently on normal cells but on most SCLC cells. 

Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Hummel.

The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.

At the meeting, Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as 10 mg.

The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients and 25.0% had brain metastases.

Doses varied among participants, with 76 patients (50%) receiving 100 mg, 32 (21%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.

The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10 mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.

Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.

Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage 30 and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.

In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Hummel concluded in his presentation.

No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses over 10 mg and 100% of patients with 10 mg doses). Overall, 67.4% of the total cohort experienced cytokine release syndrome of any grade and 12.6% developed immune effector cell-associated neurotoxicity syndrome. 

Discontinuation due to treatment-related adverse events occurred in patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall. 

“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the Oncology Department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Menis noted, because the study only included patients with stable, treated brain metastases.

And given the high rates of adverse events, Menis cautioned that adverse event management “will be a challenge.”

On X (Twitter), Tom Newsom-Davis, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatumab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.

“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ,” he added.

DeLLphi-300, 301, and 304 funded by Amgen Inc. Hummel declared relationships with several companies, including Amgen Inc, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, Roche. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, Novartis.

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