Study to Confirm Efficacy and Feasibility of Tarlatamab Treatment in Patients With Extensive Stage Small-cell Lung Cancer With Poor Performance Status

The SPACE-T study is a phase II clinical trial investigating the treatment tarlatamab in people with advanced small-cell lung cancer (SCLC). The study focuses specifically on patients whose cancer has returned or spread after previous treatment and whose general health and ability to carry out everyday activities are reduced (ECOG performance status 2). This patient group is often underrepresented in clinical trials, although it represents an important part of patients treated for SCLC in routine clinical practice.

A total of 57 patients are planned to participate at approximately 15 study sites in Germany. To take part, patients must be at least 18 years old and have confirmed small-cell lung cancer that has returned or spread to other parts of the body. They must have received at least one previous treatment for recurrent or metastatic disease. In general, previous treatment should have included platinum-based chemotherapy, etoposide and a PD-L1 inhibitor. Patients must also have cancer that can be measured on imaging examinations.

Patients with brain metastases may also participate in the study. However, patients cannot take part if brain metastases are causing new or worsening neurological symptoms. There are also other eligibility requirements relating, for example, to blood counts, liver and kidney function, breathing problems and previous cancer treatments. Patients who have previously received a treatment targeting DLL3 cannot participate.

All participants in the study will receive tarlatamab; there is no placebo or comparison group. Tarlatamab is a type of immunotherapy designed to bring the body's T cells into contact with cancer cells that carry a protein called DLL3. This is intended to help the immune system recognize and attack the cancer cells.

Tarlatamab is given through a vein. To reduce the risks associated with starting treatment, patients first receive a lower dose of 1 mg on the first day of treatment. They then receive the full 10 mg dose one week later and again one week after that. Afterwards, tarlatamab is generally given every two weeks.

The main aim of the SPACE-T study is to determine how effective tarlatamab is in this patient population. The main measure used for this assessment is the proportion of patients who are alive 12 months after starting the study. Other assessments will look at how long patients live overall, how long the cancer remains under control, how many patients have a reduction in the size of their cancer, and how long it takes before another cancer treatment is needed. For patients with brain metastases, the study will also examine how well the treatment controls cancer in the brain.

Another important aim is to understand whether tarlatamab can be given safely and practically to patients whose general health is reduced. The study will therefore closely assess side effects and how well patients tolerate treatment. It will also evaluate patients' quality of life and symptoms using questionnaires completed by the patients themselves. In addition, the study will investigate whether palliative radiotherapy, for example for symptomatic cancer lesions, can be incorporated into treatment with tarlatamab.

Blood samples and, where available as part of routine care, tumor tissue samples will also be collected for research. These samples will be used to study changes in the immune system during treatment and to investigate whether early immune responses may be related to how well a patient's cancer responds to tarlatamab.

Tarlatamab can cause specific immune-related side effects. These include cytokine release syndrome (CRS), an inflammatory reaction caused by activation of the immune system, and neurological side effects such as immune effector cell-associated neurotoxicity syndrome (ICANS). One reason for conducting the SPACE-T study is to obtain more information about the feasibility, safety and effectiveness of tarlatamab in patients with poorer general health, for whom there is currently limited clinical evidence.

Overall, the SPACE-T study aims to determine whether tarlatamab is an effective and feasible treatment option for patients with advanced small-cell lung cancer and reduced performance status, a population that more closely reflects many patients seen in everyday clinical practice.