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MADRID -- Patients with previously treated small-cell lung cancer (SCLC) obtained durable responses with either of two doses of the bispecific T cell-engaging (BiTE) antibody tarlatamab, according to a study reported here.

Overall, 36% of patients had objective responses, including 40% of those treated with the lower dose of the BiTE, selected for continued clinical evaluation. An additional 30% of patients had stable disease. A majority of responses to either dose of the drug lasted 6 months or longer.

About a third of patients had grade ≥3 treatment-related adverse events (TRAEs), but only 3% of patients discontinued treatment because of TRAEs, reported Luis Paz-Ares, MD, of Hospital Universitario 12 de Octubre in Madrid, at the European Society for Medical Oncology (ESMO) congress. The results were published simultaneously in the .

"On the basis of the safety-risk ratio, we have chosen 10 mg of tarlatamab to go to further development," he said. "At that dose, 40% of patients do have a response. At 6 months, 58% of the patients continued to be in response. Safety has been quite manageable. CRS [cytokine release syndrome] has been the main side effect, but only 1% being grade 3."

"I think these results support the use of tarlatamab in the setting of previously treated patients. There is a phase III trial ongoing that is comparing this regimen against standard-of-care chemotherapy," Paz-Ares stated.

The lower dose of tarlatamab "demonstrated encouraging results in a highly selected population and with durable anticancer activity and manageable safety in a setting of huge clinical need," said ESMO invited discussant Pilar Garrido-Lopez, MD, of Hospital Universitario Ramón y Cajal in Madrid. "But there are key challenges ahead."

Garrido-Lopez cited three areas of uncertainty:

• Applicability to real-world patients: A third of patients had received three or more prior lines of therapy and the study population had a median age of 64, whereas the proportion of patients >70 with SCLC is approaching 50%
• Toxicity issues: Inpatient-only administration is challenging for organizations and patients and many centers have limited experience with managing CRS
• Efficacy: Need for data on central nervous system activity, limited duration of follow-up, and need for relevant biomarkers

"Despite the many challenges, the emerging data offer renewed hope to patients ... with a high unmet need," she concluded.

SCLC currently has no approved therapies for third line and beyond, Paz-Ares noted. Tarlatamab binds to the delta-like ligand 3 (DLL3) on SCLC cells and to CD3 on T cells, leading to cancer-cell lysis. The BiTE demonstrated a manageable safety profile and antitumor activity in a of previously treated SCLC, leading to the phase II involving patients who had received two or more prior lines of therapy.

The trial consisted of three parts. During the first part, 176 patients were randomized to tarlatamab 10 mg or 100 mg, administered by 30-minute infusion. The second part included 12 patients who received the lower dose of tarlatamab. During part three, 34 patients received tarlatamab 10 mg but had a reduced inpatient monitoring period. Paz-Ares reported data from the first two parts of the study.

The primary outcome was objective response rate. The data showed responses in 40 of 100 patients treated with the lower dose of tarlatamab in parts one and two, including one complete response (CR). Among 88 patients treated with the higher dose, 28 (32%) had objective responses, including eight CRs. Additionally, 30 patients in the 10-mg arm and 27 in the 100-mg arm had stable disease.

Responses had a duration of 6 months or longer in 23 of 40 (58%) patients in the 10-mg arm and 17 of 28 (61%) in the 100-mg arm. The vast majority of patients in both groups had some degree of tumor shrinkage.

The median progression-free survival (PFS) was 4.9 months with tarlatamab 10 mg and 3.9 months with the higher dose. The 6-month PFS was 40.4% with 10 mg and 34.1% with 100 mg. Median overall survival (OS) was 14.3 months with the 10-mg dose and not yet reached with the 100-mg dose. OS data remain immature, but as of last follow-up (June 27, 2023), 57% of patients in the 10-mg group remained alive as were 51% of those treated with 100 mg.

Grade ≥3 TRAEs occurred in 29% of the tarlatamab 10 mg cohort and 33% of the 100-mg group. The most common treatment-emergent AE (TEAE) was CRS, which occurred in 49% of the 10-mg group and 61% of the 100-mg group. Grade ≥3 CRS occurred in five patients treated with 100 mg tarlatamab and none of those treated with 10 mg. Other all-grade TEAEs occurring in ≥20% of patients in either group were decreased appetite, pyrexia, constipation, anemia, asthenia, dysgeusia, and fatigue.

CRS occurred primarily during the first or second cycle of treatment. Immune effector cell-associated neurotoxicity occurred infrequently and was observed mostly in the 100-mg group, said Paz-Areas. Seven patients in the 10-mg group and nine in the 100-mg group received tocilizumab (Actemra) for CRS.

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