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Subcutaneous Tarlatamab Shows Promising Safety and Efficacy in Lung Cancer Trial

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Subcutaneous Tarlatamab Shows Promising Safety and Efficacy in Lung Cancer Trial

Introduction

A significant advancement in the treatment of extensive-stage small cell lung cancer (ES-SCLC) has emerged from the Phase 1b DeLLphi-308 study, presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC). The study investigated a subcutaneous (under-the-skin) formulation of tarlatamab, a bispecific T-cell engager (BiTE®) immunotherapy. This new delivery method was found to be well-tolerated, exhibiting low toxicity rates and demonstrating preliminary antitumor activity, offering a potentially more convenient option for patients with this challenging form of lung cancer.

Key Details

  • Drug: Tarlatamab, a bispecific T-cell engager (BiTE®) immunotherapy.
  • Indication: Previously treated extensive-stage small cell lung cancer (ES-SCLC).
  • Study Design: Open-label, multicenter Phase 1b trial (DeLLphi-308).
  • Administration Routes: Investigated subcutaneous versus established intravenous administration.
  • Key Findings (15 mg subcutaneous dose):
    • Treatment-related adverse events (TRAEs) occurred in 85% of patients.
    • Severe (Grade 3 or higher) TRAEs occurred in 10% of patients.
    • Most common TRAEs: injection-site reactions (50%), dysgeusia (45%), cytokine release syndrome (CRS) (38%), decreased appetite (20%).
    • No Grade 5 TRAEs were reported.
    • CRS events were predominantly Grade 1; no Grade 3 or higher CRS occurred, and no CRS required dose interruption or discontinuation.
    • Preliminary objective response rate (ORR) was 30%.
    • Pharmacokinetic profile showed serum exposures comparable to the approved 10 mg intravenous dose administered every two weeks.
  • Target Dose Selection: 15 mg subcutaneous tarlatamab every two weeks was selected based on comparable drug exposure to the intravenous regimen and a favorable safety profile.
  • Study Presentation: Findings presented at the IASLC 2026 World Conference on Lung Cancer (WCLC). Updated data to be presented on September 15.

Background

Small cell lung cancer (SCLC) is an aggressive form of lung cancer, and the extensive-stage (ES) subtype, meaning the cancer has spread widely, is particularly difficult to treat. Tarlatamab represents a novel therapeutic approach, functioning as a bispecific T-cell engager. This type of immunotherapy is designed to bridge T-cells (a type of immune cell) to cancer cells, thereby activating the immune system to attack the tumor. While tarlatamab has previously shown clinical activity when administered intravenously, the DeLLphi-308 study explored a subcutaneous formulation. This route of administration is often preferred for its convenience, potentially allowing patients to self-administer medication or receive it in an outpatient setting, reducing the need for frequent hospital visits. Furthermore, subcutaneous delivery can sometimes lead to slower absorption and lower peak drug concentrations in the blood compared to intravenous infusion, which may translate to a reduced incidence or severity of certain side effects, such as cytokine release syndrome (CRS).

“The findings from DeLLphi-308 suggest that 15 mg subcutaneous tarlatamab dose can achieve serum exposures comparable to the approved 10 mg intravenous dosing administered every two weeks while maintaining a favorable safety profile,” stated Pedro Rocha, MD, of Hospital Universitari Vall d Hebron in Barcelona, Spain, and the study’s primary author. “The predominantly low-grade CRS events and preliminary antitumor activity support continued investigation of this more convenient route of administration.”

Impact Analysis

The results from the DeLLphi-308 study are highly encouraging, particularly regarding the safety profile of subcutaneous tarlatamab. The incidence of treatment-related adverse events (TRAEs) was 85%, which is not uncommon for immunotherapies, but the critical finding is that only 10% experienced severe (Grade 3 or higher) events. This contrasts favorably with some other systemic treatments for ES-SCLC. The most frequently reported side effects were injection-site reactions and dysgeusia, which are generally manageable. Crucially, cytokine release syndrome (CRS), a potentially serious immune-related adverse event associated with T-cell engaging therapies, was predominantly low-grade (Grade 1) and did not lead to any dose interruptions or discontinuations. This suggests that the subcutaneous route may indeed mitigate the severity of CRS compared to intravenous administration, enhancing patient tolerability. The preliminary objective response rate of 30% indicates that the drug is eliciting a meaningful anti-tumor response in a significant portion of patients, aligning with the efficacy seen with the intravenous form. The comparable pharmacokinetic profile further solidifies the potential of this subcutaneous formulation to deliver equivalent therapeutic benefit.

Broader Context

The landscape of small cell lung cancer treatment has historically been limited, with chemotherapy forming the backbone for decades. While recent advances, including the addition of immunotherapy like atezolizumab or durvalumab to chemotherapy, have improved outcomes, ES-SCLC remains a disease with a high rate of relapse and significant unmet needs. Bispecific T-cell engagers like tarlatamab represent a promising next generation of therapies that harness the patient's own immune system in a more targeted manner. The development of a subcutaneous formulation is a strategic move to improve patient convenience and potentially broaden access to this innovative treatment. If proven effective and safe in larger trials, this administration route could significantly impact the patient experience, shifting treatment paradigms towards more accessible and less burdensome options, especially for patients with advanced disease who may already be frail.

Future Outlook

The positive findings from this Phase 1b study provide a strong rationale for the continued development of subcutaneous tarlatamab. The 15 mg dose, administered every two weeks, has been selected for further investigation, likely in Phase 2 and Phase 3 trials. These larger studies will be crucial to confirm the efficacy and safety of this formulation in a broader patient population and to compare it more definitively against existing standards of care. Updated data from the study are anticipated soon, which will provide further insights into the ongoing treatment responses and potential long-term effects. Success in these future trials could lead to regulatory approval, offering patients with ES-SCLC a new, potentially more convenient, and well-tolerated treatment option.

Conclusion

The DeLLphi-308 study represents a significant step forward in the management of extensive-stage small cell lung cancer. The subcutaneous administration of tarlatamab has demonstrated a favorable safety profile, characterized by low rates of severe adverse events and manageable side effects, including a notable reduction in the severity of CRS. Coupled with preliminary evidence of anti-tumor activity and comparable drug exposure to the intravenous form, this new delivery method holds considerable promise. The potential for improved patient convenience further enhances its appeal. These encouraging results warrant the continued investigation of subcutaneous tarlatamab in ongoing and future clinical trials, offering hope for a more accessible and effective treatment for patients battling this aggressive disease.

Source: news-medical.net

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