A single-arm phase II-study to confirm efficacy and feasibility of tarlatamab treatment in patients with extensive stage small-cell lung cancer with poor performance status (SPACE-T) [without IMPD-Q]

The primary objective of this study is to prospectively evaluate the efficacy of tarlatamab treatment in patients with extensive stage small-cell lung cancer and poor performance status. This objective addresses a clinically significant unmet need, as patients with compromised functional status often have limited therapeutic options and are underrepresented in clinical trials, making the assessment of tarlatamab efficacy in this vulnerable population critically important for informing treatment decisions.

The secondary objectives include:

• Evaluate efficacy, feasibility, quality of life, and toxicity of tarlatamab in patients with extensive stage small-cell lung cancer and poor performance status.

• Evaluate feasibility, intracranial efficacy, quality of life, and toxicity of tarlatamab in patients with brain metastases.

• Evaluate feasibility of embedding palliative radiation with tarlatamab treatment.

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population includes **adult** participants aged 18 years and older, with both **male** and **female** subjects eligible for enrollment. Participants are patients diagnosed with histologically confirmed **small-cell lung cancer**, specifically those with **extensive stage** disease and **poor performance status**, defined as an **ECOG performance status** of 2. The trial population consists of individuals with **recurrent** or **metastatic disease** who have received at least one prior line of treatment in the recurrent or metastatic setting, including prior therapy with **platinum**, **etoposide**, and a **PD-L1 antibody**. Patients with initial mixed histology or combined small-cell lung cancer are permitted if re-biopsy demonstrates small-cell lung cancer. The trial includes a vulnerable population and requires participants to have **measurable disease** according to **RECIST v1.1** criteria. Participants must have provided written informed consent prior to any protocol-related procedures.

This study is designed as a **single-arm phase II clinical trial** to evaluate the efficacy and feasibility of **tarlatamab** treatment in patients with **extensive stage small-cell lung cancer** who have a **poor performance status**. The trial investigates tarlatamab, a **protein-based investigational medicinal product** administered as a **powder for solution for infusion** via **intravenous infusion**, with a maximum daily dose of **10 mg** and a maximum total dose of **241 mg** over a treatment period of up to **12 months**. The primary objective is to prospectively assess the efficacy of tarlatamab in this specific patient population with **ECOG performance status 2**.

The trial employs a non-randomized, open-label design without blinding or control group comparison. Eligible participants must be adults aged 18 years or older with histologically confirmed small-cell lung cancer, recurrent or metastatic disease, and measurable disease according to **RECIST v1.1** criteria. Participants must have received at least one prior line of treatment in the recurrent or metastatic setting, including prior therapy with platinum, etoposide, and a **PD-L1 antibody**, or chemotherapy alone if contraindications to checkpoint inhibitor treatment existed. Written informed consent is required prior to any protocol-related procedures.

The primary endpoint is the **overall survival rate at 12 months**. Secondary endpoints include overall survival, **progression-free survival**, **objective response rate** according to RECIST v1.1, **intracranial objective response rate**, the rate of patients tolerating tarlatamab until first disease assessment, time to next-line systemic therapy, safety and tolerability, and quality of life assessed using **EORTC-QLQ-C30** and **PRO CTCAE** instruments. The study is scheduled to commence recruitment in January 2026 and is estimated to conclude in January 2030, representing an overall trial duration of approximately four years.

Participant involvement begins with a screening visit to confirm eligibility based on inclusion criteria. Following enrollment, participants receive tarlatamab treatment according to the protocol-specified dosing schedule and attend regular follow-up visits for disease assessment, safety monitoring, and quality of life evaluation. The first disease assessment occurs after initiation of treatment to evaluate tolerability and response. Subsequent follow-up visits are conducted at defined intervals throughout the treatment period to assess tumor response, monitor for disease progression, and evaluate adverse events. Participants may remain in the study for up to 12 months of active treatment, with continued follow-up for survival assessment. An end-of-study visit is conducted upon completion of the treatment period or upon early discontinuation. Early termination from the study may occur due to disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified reasons that prevent continuation of treatment or follow-up.

The experimental medication evaluated in this clinical trial is **Tarlatamab** (sponsor product code AMG 757), a **bispecific T-cell engager** protein therapeutic. Tarlatamab is supplied as a **powder for solution for infusion** and is administered via **intravenous infusion**. The active substance is tarlatamab, which is classified as a protein of non-recombinant origin. The maximum daily dose is **10 mg**, with a maximum total dose of **241 mg** administered over the course of treatment. The maximum treatment period is **12 months**. The dosing regimen involves systematic administration to patients with **extensive stage small-cell lung cancer** who have poor performance status, with the objective of evaluating the efficacy and feasibility of this therapeutic approach in this specific patient population.

Efficacy will be assessed through multiple parameters in this clinical trial. The primary endpoint is the overall survival rate at 12 months. Secondary efficacy endpoints include overall survival, progression-free survival, objective response rate according to RECIST v1.1, intracranial objective response rate according to RECIST v1.1, rate of patients tolerating tarlatamab until first disease assessment, and time to next-line systemic therapy. Quality of life will be evaluated using the EORTC-QLQ-C30 questionnaire and PRO CTCAE patient-reported outcomes. Disease response will be measured using RECIST version 1.1 criteria for both systemic and intracranial assessments.