Tarlatamab Demonstrates Preliminary Antitumor Efficacy in Heavily Pretreated SCLC

Hossein Borghaei, DO, MS

Tarlatamab (AMG 757), a DLL3-targeted immunotherapy, showed anti-tumor activity with promising response duration in patients with heavily pretreated small cell lung cancer (SCLC), according to interim phase 1 study findings presented during the 2022 World Conference on Lung Cancer.¹

The confirmed objective response rate (ORR) observed with tarlatamab treatment in the study was 23%. Out of 106 patients, there were notably 2 complete responses and 22 partial responses. Thirty-seven percent of the study population had target lesion shrinkage of ≥ 30. Stable disease was seen in 31 patients, and progressive disease occurred in 8 patients. The disease control rate was 52%.

The median duration of response was 13.0 months (95% CI, 6.2-14.9 months). Of the patients who responded to treatment with tarlatamab, 11 patients were continuing treatment at the time of data cutoff. The median time to response was 1.8 months (range, 1.2-7.4 months).

“Finding treatments that are effective in metastatic small cell lung cancer has been challenging, just because this is a very, very aggressive disease,” said Hossein Borghaei, DO, MS, chief of Thoracic Medical Oncology and a professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, in a press release.² “So, this drug, if successful, would address a significant unmet need.”

The open-label, multicenter study of tarlatamab (DELLphi-300, NCT03319940) is primarily evaluating the safety and tolerability of the agent in patients with SCLC and determining its maximum-tolerated dose and recommended phase 2 dose. The secondary end points of the study include pharmacokinetics and preliminary antitumor activity. As exploratory end points, the study is assessing the immunogenicity of tarlatamab and biomarker utility.¹

DELLphi-300 included patients with histologically or cytologically confirmed disease that progressed or recurred following at least 1 platinum-based chemotherapy, an ECOG performance status of 0-1, and ≥ 2 measurable lesions. At baseline, the population had a median age of 64 years (32-80 years) and a median of ≥ 3 prior lines of therapy.

In addition to antitumor activity, tarlatamab achieved a median overall survival of 13.2 months (95% CI, 8.8 to not reached. The median progression-free survival was 3.7 months (95% CI, 2.1-5.3 months).

Treatment-related adverse events (TRAEs) of any grade occurred in 92% of patients in the study. Thirty-one percent of the TRAEs observed in the study were grade ≥ 3. The most common any-grade TRAEs included cytokine release syndrome (CRS; 53%), pyrexia (38%), dysgeusia (23%), fatigue (22%), and nausea (20%). Come grade ≥ 3 events including fatigue (3%), pyrexia (2%), and CRS (1%).

Four percent of patients in the study discontinued treatment with tarlatamab because of TRAEs including pneumonitis (n = 2), encephalopathy (n =1), neurotoxicity (n = 1), and pneumonitis (n = 2).

TRAES of interest included CRS, neurologic events, and neutropenia. Cases of CRS were largely grade 1 and rarely recurred. There were no events of grade 4 or 5 CRS during the study. Neurologic events were also predominantly low grade, but 5 patients experienced grade ≥ 3 confusion. Grade 4 neutropenia occurred in 4 patients. There were no febrile neutropenia events.

Across all dose levels assessed, tarlatamab displayed a manageable safety profile.

Based on the positive phase 1 results, a phase 3 registrational study of tarlatamab (DELLphi-201; NCT05060016) has been initiated in patients with SCLC who have received ≥ 2 prior lines of therapy.

_REFERENCES:

_{1. Borghaei H, Paz-Ares L, Johnson M, et al. Phase 1 updated exploration and first expansion data for DLL3-targeted t-cell engager tarlatamab in small cell lung cancer. Presented at: International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria. Abstract OA12.05}

_{2. Tarlatamab shows efficacy against metastatic small cell lung cancer in phase 1 study. News release. Fox Chase Cancer Center. August 8, 2022. Accessed August 10, 2022. https://bit.ly/3Qh7JaY}