Evaluation of Safety and Efficacy of Serplulimab Plus Chemotherapy in Patients With Histological Transformation From EGFR-mutated NSCLC to SCLC After Treatment: a Single-arm, Multicenter, Open-label Phase II Study

Plain English Summary

Safety and Efficacy Evaluation of Serplulimab Plus Chemo in SCLC Transformed From EGFR-mutated NSCLC After Treatment is a Phase 2 clinical trial sponsored by Guangdong Association of Clinical Trials studying Small-cell Lung Cancer. This trial tests a combination of Serplulimab (an immunotherapy drug) and chemotherapy. It is for patients whose non-small cell lung cancer (NSCLC) with an EGFR mutation has transformed into small-cell lung cancer (SCLC). Patients will receive the study drugs intravenously. Participation involves regular clinic visits for treatment and monitoring. Standard chemotherapy is the current alternative for this condition. The trial aims to enroll 36 participants.

Official Summary

This investigator-initiated, open-label, prospective Phase II clinical trial, planned to take place across multiple centers in China. We design this trial to evaluate the safety and efficacy of Serplulimab plus chemotherapy in SCLC transformed from EGFR-mutated NSCLC after treatment.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18-75 who have a confirmed diagnosis of lung cancer that started as EGFR-mutated NSCLC and has now transformed into SCLC. Patients must not have received systemic therapy or anti-PD-1/L1/CTLA-4 therapy after their cancer transformed. Must have at least one measurable tumor and good organ function. Patients with stable brain metastases may be eligible. Individuals with severe allergies to study drugs, active infections, or certain heart conditions may not be eligible. This trial is studying Small-cell Lung Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

Progression-free survival (PFS) measures how long patients live without their cancer getting worse, indicating how well the treatment controls the disease. The specific primary outcome measures are: Progression free survival (PFS) (From date of first dosing to first documented progression or death from any cause, whichever came first, assessed up to 2 years.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical unmet need for patients whose lung cancer changes type after initial treatment, offering a new combination therapy approach. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Small-cell Lung Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a specific, difficult-to-treat lung cancer subtype, potentially offering a new treatment option and representing an investment in novel combination therapies. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific chemotherapy drugs used and potential side effects. Understand the schedule of clinic visits for infusions and monitoring. Discuss any other medical conditions or medications you are taking with the study team. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 36 participants

Interventions

• DRUG: Serplulimab — serplulimab 300mg, d1, q3w, iv. etoposide 100 mg/m2, d1-3, q3w, iv. carboplatin AUC 5 (up to 750mg), d1, q3w, iv.
• DRUG: SOC — the treatment recommended by the investigator

Primary Outcomes

• Progression free survival (PFS) (From date of first dosing to first documented progression or death from any cause, whichever came first, assessed up to 2 years.)

Secondary Outcomes

• Objective Response Rate (Up to 2 years)
• Overall survival (OS) (Up to approximately 2 years)

Full Eligibility Criteria

Inclusion Criteria:

* Volunteer to participate in clinical studies.
* Age 18-75 (including the cut-off value) when signing the Informed Consent Form (ICF)
* Patients must provide pathological diagnosis reports and genetic testing reports before transformation, and the reports clearly indicate that they were non-small cell lung cancer containing EGFR mutations before transformation.
* Patients must provide a pathological diagnosis report after transformation, as well as 10 unstained reports after transformation. The pathology of the patients after transformation was SCLC or high-grade neuroendocrine carcinoma or containing SCLC components.
* Patients who have not received systemic therapy and anti-PD-1/L1 and CTLA-4 therapy after tissue type transformation. Patients are allowed to receive immunotherapy before transformation, but the last line of therapy cannot contain immunotherapy.
* The end of previous anti-tumor treatment must be more than 2 weeks from the first medication in this study, and the treatment-related AE should be recovered to CTCAE 5.0 ≤ grade 1 (except for grade 2 alopecia).
* At least one measurable target lesion based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria identified within the four weeks leading up to the initial treatment dose
* ECOG PS 0 or 1
* Expected life expectancy of 12 weeks or more
* Adequate organ function
* The serum pregnancy test of female patients must be negative within 14 days before treatment, and effective contraceptive measures should be taken during treatment and within 6 months after treatment. Lactation is prohibited during treatment.
* Male patients must agree to abstinence (avoid heterosexual intercourse) or take contraceptive measures.

Exclusion Criteria:

* Patients cannot provide a pathology report after tissue type transformation.
* Patients with a known history of severe allergies to any monoclonal antibody ( NCI-CTCAE 5.0 grade greater than grade 3 ); or known hypersensitivity to carboplatin/etoposide components.
* Patients with known or screening findings of active central nervous system (CNS) metastases and/or cancerous meningitis (Exceptions will be made for patients with asymptomatic brain metastases or those who have had stable brain metastases for at least 4 weeks after treatment)
* Patients who have received systemic therapy or other immune checkpoint inhibitors after tissue type transformation; patients who are preparing for or have previously received organ or bone marrow transplantation.
* Any active infection requiring systemic anti-infectious therapy within 14 days before the first administration.
* Myocardial infarction or poorly controlled arrhythmia has occurred within 6 months before the first administration; or according to the NYHA standard III-IV cardiac insufficiency or echocardiography left ventricular ejection fraction \< 50 %; or pleural effusion, pericardial effusion or ascites requiring clinical intervention.
* Patients have uncontrolled or symptomatic hypercalcemia; Patients have poor blood pressure control; patients with deep vein thrombosis, being treated with anticoagulant or platelet therapy, or previous deep vein thrombosis or severe bleeding caused by the use of anti-angiogenic drugs; Patients with known active or suspected autoimmune diseases (Patients in a stable state who do not require systemic immunosuppressive therapy are allowed to be enrolled).
* Patients who have been and were screened and judged by the investigator to be likely to interfere with the detection and management of suspected drug-related lung toxicity; Patients who the investigator believes have any factors that are inappropriate for participating in this trial.
* Patients with hepatitis B; or hepatitis C patients; or syphilis screening positive; or known human immunodeficiency virus ( HIV ) positive history or HIV screening positive; known history of mental drug abuse or drug abuse.
* Other active malignancies tumors within 5 years or concurrently.
* Patients who were vaccinated with live or attenuated vaccines within 28 days before the first dose, or had plans to vaccinate such vaccines during the study period (but inactivated virus vaccines for seasonal influenza are allowed) or who underwent major surgery.
* Patients with spinal cord compression who have not been radically cured by surgery and/or radiotherapy. Received radical radiotherapy within 3 months before the first administration.
* Patients who were participating in other clinical studies, or who participated in any other clinical trials (including drugs and devices, etc.) and received intervention within 3 months or 5 half-lives (whichever is longer) before screening.

Trial Locations

• Guangdong Provincial Perople's Hospital, Guangzhou, Guangdong, China

Frequently Asked Questions

Related Conditions

• Small-cell Lung Cancer
• Non-small cell lung cancer
• EGFR-mutated lung cancer
• Lung cancer transformation
• Neuroendocrine tumors
• Chemotherapy
• Immunotherapy
• Targeted therapy
• Oncology
• Thoracic oncology

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