Bispecific Tarlatamab Elicits Responses in Patients With Pretreated SCLC

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Tarlatamab induced a 40% objective response rate among patients with pretreated small cell lung cancer—including many patients who had already received 3 lines of therapy.

Luis Paz-Ares, MD, PhD

Luis Paz-Ares, MD, PhD

The phase 2 DeLLphi-301 (NCT05060016)study showed that patients with previously treated small cell lung cancer (SCLC) achieved encouraging responses with the bispecific T-cell engager tarlatamab. Findings were presented at the European Society for Medical Oncology Congress 2023.

Key Findings

Researchers conducting this study enrolled patients with extensive-stage SCLC whose disease relapsed after at least 2 prior lines of therapy, including a platinum-based regimen either with or without a checkpoint inhibitor. In Part 1 of this study, patients were randomly assigned to receive tarlatamab either at a 10-mg dose (n = 100) or a 100-mg dose (n = 88).

The objective response rate (ORR) for patients treated with the 10-mg dose was 40% (97.5% CI, 29-52) vs 32% (97.5% CI, 21-44) with the 100-mg dose. The rate of patients who responded to tarlatamab for at least 6 months was 58% in the 10-mg group and 61% in the 100-mg group.

“Tarlatamab has shown manageable safety profile and activity,” Luis Paz-Ares, MD, PhD, chair of the medical oncology department at the Hospital Doce de Octubre, associate professor at the Universidad Complutense, and head of the lung cancer unit at the CNIO in Madrid, Spain, said during the presentation of the data. “We have chosen 10 milligrams to go to further development.”

Behind The Numbers

As Paz-Ares explained, SCLC is an aggressive form of cancer and patients with this malignancy face poor survival outcomes. Specifically, there are no approved therapies in the third-line or beyond. However, tarlatamab showed manageable safety and encouraging efficacy data in a phase 1 study of pretreated patients with SCLC. Paz-Ares expressed optimism about targeting pretreated SCLC with this approach.

“Tarlatamab is a BiTE, bispecific T-cell engager, that binds to DLL3 on the small cell lung cancer cell, and also to the CD3 receptor on the T cell. In turn, it activates the T cells to produce the cancer cell lysis,” Paz-Ares said during the presentation.

The primary end point of this study was ORR, assessed by blinded independent central review. Other end points of interest included progression-free survival (PFS), median duration of response (mDOR), overall survival (OS) and treatment-emergent adverse events (TEAEs). Follow-up was conducted for a median of 10.6 months.

Regarding baseline characteristics, the median age of patients in the 10-mg group was 64 years (range, 35-82) and 62 years (range, 34-80) in the 100-mg group. The percentage of patients who had received at least 3 prior lines of therapy was 33% and 43%, respectively, and the rate of prior anti-PD-(L)1 treatment was 73% and 70%. In both arms, the rate of DLL3 expression was 96%.

“There was no difference in the tumor reduction based on DLL3 expression,” Paz-Ares said. “Indeed, most patients expressed DLL3.”

Secondary Outcomes

The median time to objective response was 1.4 months (range, 1.1-9.6) in both groups, and the mDOR was not reached. Of the 68 patients who responded to treatment, the duration of response was 6 months or longer in 40 patients (59%). Of note, 56% of the responses to treatment were ongoing at the data cutoff.

In patients treated with either the 10-mg or 100-mg dose, the median PFS was 4.9 months (95% CI, 2.9-6.7) and 3.9 months (95% CI, 2.6-4.4), respectively, and the median OS was 14.3 months (95% CI, 10.8-not estimable [NE]) and NE (95% CI, 12.4-NE).

Paz-Ares noted that the OS data were not mature, but at the last follow-up, 57% of patients in the 10-mg group and 51% of those in the 100-mg group were still alive.

The most common TEAE was cytokine release syndrome (CRS), which occurred in 49% of patients in the 10-mg group and 61% of those in the 100-mg group. CRS primarily occurred during cycle 1 and was mostly considered grade 1 or 2. Although low, there were some instances of grade 3 CRS; these were reported by 5.7% of those treated with the 100-mg dose.

TEAEs that led to either dose interruption or reduction occurred in 14% of patients treated with the 10-mg dose and 29% in those treated with the 100-mg dose.

Immune effector cell-associated neurotoxicity syndrome (ICANS), which included associated neurologic events, occurred infrequently and were primarily observed with the 100-mg dose of tarlatamab.

“Tarlatamab represents a new immunotherapeutic approach for small-cell lung cancer, a tumor type that is characterized by an immunosuppressive microenvironment,” the researchers wrote in the simultaneous publication of the findings in The New England Journal of Medicine.

In the paper, the researchers concluded that longer follow-up of patients in this study will provide more information about the long-term durability of response to the treatment, in addition to long-term survival benefits.

References

  1. Paz-Ares L, Ahn M, Felip E, et al. Tarlatamab for patients (pts) with previously treated small cell lung cancer (SCLC): Primary analysis of the phase II DeLLphi-301 study. Presented at: European Society for Medical Oncology Congress 2023; October 20-24, 2023; Madrid, Spain. Abstract LBA92.
  2. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. Published online October 20, 2023. doi:10.1056/NEJMoa2307980
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