Tarlatamab with carboplatin/etoposide and atezolizumab for EGFR‑mutant lung adenocarcinoma that changed into small cell lung cancer

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: Phase II Multicenter Clinical Trial

This trial tests whether adding tarlatamab to standard platinum‑etoposide chemotherapy and atezolizumab helps patients whose EGFR‑mutant lung adenocarcinoma has transformed into small cell lung cancer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: Samsung Medical Center (other)
• Drugs / interventions: tarlatamab, atezolizumab, chemotherapy, radiation, durvalumab
• Locations: 1 site (Seoul, Gangnam-gu)
• Trial ID: NCT06830694 on ClinicalTrials.gov

What this trial studies

This is a phase 2, single‑center, interventional trial combining tarlatamab (a DLL3‑directed bispecific T‑cell engager) with carboplatin and etoposide plus the PD‑L1 inhibitor atezolizumab in patients whose EGFR‑mutant lung adenocarcinoma has histologically transformed into small cell lung cancer after EGFR TKI failure. Eligible patients are adults with ECOG 0–1, no prior systemic therapy for the transformed SCLC, at least one measurable lesion, and adequate organ function. The regimen is given systemically with safety and clinical activity monitored by imaging and labs according to protocol schedules. The primary goals are to characterize safety and clinical benefit of the combination in this specific, post‑EGFR‑TKI transformed population.

Who should consider this trial

Good fit: Ideal candidates are adults (≥19 years) with confirmed SCLC transformation after prior EGFR TKI therapy for EGFR‑mutant adenocarcinoma, ECOG 0–1, no prior systemic SCLC treatment, measurable disease, and adequate blood, liver, and kidney function.

Not a fit: Patients with poor performance status (ECOG ≥2), significant organ dysfunction, prior systemic therapy for SCLC, or who cannot travel to the study site are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could offer improved tumor control and a new treatment option for patients whose EGFR‑mutant lung cancer has transformed into small cell disease.

How similar studies have performed: Early trials of tarlatamab and other DLL3‑directed agents have shown promising activity in de novo SCLC, but combining such agents with platinum‑based chemo and PD‑L1 blockade in transformed SCLC remains largely untested.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed SCLC and no prior systemic treatment for SCLC
2. Patient initially diagnosed with activating EGFR mutation (L858R, Del 19) and treated with any kind of EGFR TKI.
3. Confirmed SCLC transformation right after EGFR TKI treatment failure.
4. Age ≥19 years
5. ECOG performance status of 0 to 1
6. Had at least one measurable lesion.
7. Adequate organ function

   * Absolute neutrophil count ≥ 1.5 x 109/L
   * Platelet count ≥ 100 x 109/L
   * Hemoglobin ≥ 9 g/dL
   * Estimated glomerular filtration rate based on Modification of Diet in Renal Disease calculation \> 30 mL/min/1.73 m2
   * Aspartate aminotransferase and alanine aminotransferase ≤ 3 x upper limit of normal (ULN) (or ≤ 5 x ULN for subjects with liver involvement)
   * Total bilirubin ≤ 1.5 x ULN (or ≤ 2 x ULN for subjects with liver metastases)
   * Prothrombin time (PT)/international normalized ratio and partial thromboplastin time or activated partial thromboplastin time ≤ 1.5 x institutional ULN Note: Subjects on stable anticoagulation therapy are allowed.
8. Pulmonary function: No clinically significant pleural effusion at the timepoint of screening. Pleural effusion with no significant symptom is allowed for enrollment.
9. Cardiac function: Cardiac ejection fraction ≥ 50%
10. Female subjects must either be of non-reproductive potential
11. Female subject with reproductive potential can be enrolled with agreement to following guidance.

    * subject uses contraception during treatment and through 60 days after receiving last dose of tarlatamab or for 6 months after last dose of carboplatin and/or etoposide and 5 months after last dose of atezolizumab.
12. Subject is willing and able to comply with the protocol
13. Signed written informed consent

Exclusion Criteria:

1. Treated with additional chemotherapy after confirmed with transformed SCLC.
2. Previously exposed to the immune checkpoint inhibitor treatment.
3. Untreated symptomatic brain metastases or leptomeningeal disease.

   * Asymptomatic brain metastases can be enrolled per investigator decision
4. Uncontrolled systemic illness including uncontrolled hypertension, active bleeding, or active infection.
5. Past medical history of interstitial lung disease, drug induced interstitial lung disease, radiation pneumonitis which required steroid treatment, active non- infectious pneumonitis
6. Active or prior documented autoimmune or inflammatory disorders
7. Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association \> class II) within 6 months prior to first dose of study treatment
8. History of solid organ transplant.
9. Major surgical procedures within 28 days prior to first dose of study treatment.
10. History of allergic reactions or acute hypersensitivity reactions to antibody therapies, platinum chemotherapy, or etoposide.
11. Disagree to the guidance of contraception during the study.

Where this trial is running

Seoul, Gangnam-gu

• Samsung Medical Center — Seoul, Gangnam-gu, South Korea (RECRUITING)

Study contacts

• Study coordinator: Myung-Ju Ahn, MD, PhD

Conditions: Small Cell Carcinoma of Lung