Clinical Trial for Safety and Effectiveness Evaluation of Tarlatamab (AMG757) With Etoposide, Carboplatin and Atezolizumab in Transformed Small Cell Lung Cancer Patients From Adenocarcinoma After EGFR TKI Treatment

Sponsor
Se-Hoon Lee
Study ID
NCT06830694
Phase
PHASE2
Status
Recruiting
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Conditions

  • Small Cell Carcinoma of Lung

Eligibility Criteria

Sex
ALL
Age
19 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

The primary treatment option for non-small cell lung cancer (NSCLC) adenocarcinoma (ADC) with activating epidermal growth factor receptor (EGFR) mutation is EGFR tyrosine kinase inhibitor (TKI). After a certain period of treatment with EGFR TKI, acquired resistance emerges most frequently with a secondary mutation, p.T790M (36-50%), followed by MET amplification (10-19%). Interestingly, up to 3-5% of patients experience histological transformation into small cell lung cancer (SCLC). As an underlying mechanism, ADC with a predisposed clonally inactivated Rb and p53 mutation and APOBEC mutation signature is known to be associated with SCLC transformation. The transformed SCLC harbors similar morphological and immunohistochemical (IHC) characteristics as those observed in de novo SCLC, including high expression of chromogranin and synaptophysin. However, little is known about the clinical outcomes of transformed SCLC, with limited studies arguing that their outcomes are similar to those of de novo SCLC, where the median overall survival is approximately 9 to 10 months after the transformation. As the first line treatment of SCLC, atezolizumab or durvalumab with four cycles of conventional chemotherapy followed by maintenance therapy demonstrated prolonged overall survival (OS) and placed as the standard treatment option. However, median progression-free survival (PFS) of both study was only 5.2 months and 5.1 months, despite the objective response rate showing 60.2% and 79%. This finding suggest further development of maintenance treatment strategy to prolonged longer duration of response to the treatment. In addition to the conventional treatment, Tarlatamab (AMG757), bispecific t-cell engager (BiTE), designed to engage DLL3 on SCLC and CD3 on T-cell has been tested in SCLC. DLL3 is expressed in more than 80% of patients with SCLC, regardless of disease stage and researched for the potential target protein for the antibody based treatment in SCLC. By targeting DLL3 using Tarlatamab, engagement of tumor antigen and CD3 lead to cytotoxic synapse formation, triggering the release of proinflammatory cytokines, perforin, and granzymes from activated T-cells, potentially resulting apoptosis. The first clinical outcome of Tarlatamab was reported from the DeLLphi-300 study, phase 1 dose exploration study, showing confirmed partial response in 23% of the heavily treated SCLC and 37% of the patients showed decrease in tumor burden. Median duration of response was 13.0 months (95% confidential interval CI: 6.2 - 14.9 months), median PFS of 3.7 months and median OS was 13.2 months. In the treatment naïve SCLC, DeLLphi-303 study, phase 1b study combining tarlatamab + PD-L1 inhibitor + carboplatin and etoposide, is ongoing to evaluate the clinical efficacy in the front line setting which include only histologically confirmed extensive disease SCLC population (NCT05361395). Based on previous clinical and pre-clinical outcomes, showing similar disease characteristics between transformed SCLC from the adenocarcinoma who treated with EGFR TKI with de novo SCLC, this study is designed to evaluate the clinical efficacy of tarlatamab with currently standard treatment in transformed SCLC.

Key Dates

Start date
May 13, 2025
Status verified
Feb 2026
Primary completion
Mar 31, 2027
Completion
Jun 30, 2027

Study Design

Enrollment
50 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Single arm
    * Concomitant Chemotherapy Phase: for 4 cycles Q3W Cycle 1 (21-day cycle): Atezolizumab 1200 mg IV followed by carboplatin to match AUC 5.0 IV on day 1 and then etoposide 100 mg/m2 IV on day 1- day 3. * Maintenance Tarlatamab Q2W plus Atezolizumab Q4W Cycle 5 (28-day cycle): Atezolizumab 1200 mg IV Q4W on day 1 followed by tarlatamab 1mg IV on day 1 and 10mg IV on day 8 and Day 15 in the maintaining setting. From C6 Atezolizumab 1200 mg IV Q4W on day 1 followed by tarlatamab 10mg IV on day 1 and day 15 will be applied.

Primary Outcome Measure

Progression-free survival(PFS) [ Time Frame: Up to 6months ]

Central Contacts

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