Study of Low-Dose Radiotherapy Concurrent Chemotherapy With Serplulimab for Patients With ES-SCLC

Phase 2

Recruiting

• Conditions: Extensive-stage Small-cell Lung Cancer
• Interventions: Drug: serplulimab; Drug: Cisplatin; Drug: Carboplatin; Drug: Etoposide; Radiation: Thoracic radiation therapy (TRT)

• Registration Number: NCT05765825
• Lead Sponsor: Sichuan University

Brief Summary

This is a Phase II, single arm, multicenter study designed to evaluate the safety and efficacy of low-dose radiotherapy (LDRT) concurrent cisplatin/carboplatin plus etoposide with serplulimab in participants who have extensive-stage small cell lung cancer (ES-SCLC) and are chemotherapy-navïe for their extensive-stage disease.

Detailed Description

Enrolled patients will receive the following treatment regimen: LDRT-concurrent cisplatin/carboplatin plus etoposide in combination with serplulimab. The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy at 15Gy/5f will be performed concurrently from Day 1 to Day 5 (D1-D5) of Cycle 1. An efficacy assessment will be performed at the end of Cycle 2 and one week before the start of Cycle 3. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD, low-dose radiotherapy at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 3. For subjects evaluated as PD/SD/PR with extrathoracic residual metastases, low-dose radiotherapy at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. Definition of extrathoracic lesions for radiotherapy: Metastases to liver, metastases to adrenals and metastases to lymph nodes (at the discretion of the investigator).

After the induction period, the subjects will continue to receive maintenance treatment with serplulimab. Prophylactic cranial irradiation (PCI) is allowed for treatment according to local standard of care. Patients will be treated until loss of clinical benefit, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurs first.

Study Timeline

• Study First Submitted: 2023-03-01
• Study First Submitted QC: 2023-03-01
• Study Start: 2023-03-07
• Study First Posted: 2023-03-13
• Status Verified: 2024-06
• Primary Completion: 2024-06
• Last Update Submitted: 2024-06-17
• Last Update Posted: 2024-06-20
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 61

Inclusion Criteria

1. Histologically or cytologically confirmed ES-SCLC
2. No prior treatment for ES-SCLC
3. Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.
4. ECOG performance status of 0 or 1
5. Life expectancy >= 3 months
6. Adequate hematologic and end-organ function
7. For participants receiving therapeutic anticoagulation: stable anticoagulant regimen
8. Negative human immunodeficiency virus (HIV) test at screening
9. Negative hepatitis B surface antigen (HBsAg) test at screening
10. Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: Negative total hepatitis B core antibody (HBcAb), or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test. The HBV DNA test will be performed only for participants who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test.
11. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for participants who have a positive HCV antibody test.
12. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception
13. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm

Main

Exclusion Criteria

1. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
2. Participants with pulmonary artery invasion
3. History of leptomeningeal disease
4. Uncontrolled tumor-related pain
5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
6. Uncontrolled or symptomatic hypercalcemia
7. Active or history of autoimmune disease or immune deficiency
8. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
9. Active tuberculosis
10. Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
11. History of malignancy other than small cell lung cancer (SCLC) within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab	Thoracic radiation therapy (TRT)	Participants will receive the following treatment regimens: The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy(LDRT) at 15Gy/5f will be performed concurrently from Day 1 to Day 5 (D1-D5) of Cycle 1. An efficacy assessment will be performed at the end of Cycle 2. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 3. For subjects evaluated as PD/SD/PR with extrathoracic residual metastases, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. After the induction period, the subjects will continue to receive maintenance treatment with serplulimab.
LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab	serplulimab	Participants will receive the following treatment regimens: The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy(LDRT) at 15Gy/5f will be performed concurrently from Day 1 to Day 5 (D1-D5) of Cycle 1. An efficacy assessment will be performed at the end of Cycle 2. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 3. For subjects evaluated as PD/SD/PR with extrathoracic residual metastases, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. After the induction period, the subjects will continue to receive maintenance treatment with serplulimab.
LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab	Cisplatin	Participants will receive the following treatment regimens: The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy(LDRT) at 15Gy/5f will be performed concurrently from Day 1 to Day 5 (D1-D5) of Cycle 1. An efficacy assessment will be performed at the end of Cycle 2. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 3. For subjects evaluated as PD/SD/PR with extrathoracic residual metastases, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. After the induction period, the subjects will continue to receive maintenance treatment with serplulimab.
LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab	Carboplatin	Participants will receive the following treatment regimens: The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy(LDRT) at 15Gy/5f will be performed concurrently from Day 1 to Day 5 (D1-D5) of Cycle 1. An efficacy assessment will be performed at the end of Cycle 2. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 3. For subjects evaluated as PD/SD/PR with extrathoracic residual metastases, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. After the induction period, the subjects will continue to receive maintenance treatment with serplulimab.
LDRT concurrent cisplatin/carboplatin + etoposide + serplulimab	Etoposide	Participants will receive the following treatment regimens: The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy(LDRT) at 15Gy/5f will be performed concurrently from Day 1 to Day 5 (D1-D5) of Cycle 1. An efficacy assessment will be performed at the end of Cycle 2. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 3. For subjects evaluated as PD/SD/PR with extrathoracic residual metastases, ldrt at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. After the induction period, the subjects will continue to receive maintenance treatment with serplulimab.

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	Baseline up to approximately 24 months	The time from the date of first dosing of serplulimab to the first appearance of objective disease progression (according to RECIST1.1) or death from any cause (if it occurs before disease progression).

Secondary Outcome Measures

Name	Time	Method
Disease control rate (DCR)	Baseline up to approximately 24 months	defined as the proportion of participants who have a best overall response of CR or PR or stable disease (SD), as determined by the investigator according to RECIST v1.1.
Overall Survival (OS)	Baseline up to approximately 24 months	The time from the date of first dosing of serplulimab to death from any cause.
OS Rate at 1 Year and 2 Years	Baseline to 2 years or death, whichever occurs first.	OS rate at 1 year and 2 years, defined as the proportion of patients who have not experienced death from any cause at 1 year and 2 years.
PFS Rate at 6 Months and 1 Year	Baseline up to 1 year	PFS rate at 6 months and 1 year, defined as the proportion of patients who have not experienced disease progression or death from any cause at 6 months and 1 year separately, as determined by the investigator according to RECIST v1.1.
Duration of response (DOR)	Baseline to disease progression or death from any cause (whichever occurs first)(up to approximately 24 months)	defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.
Percentage of Participants With Adverse Event	Baseline up to approximately 36 months	• The incidence and severity of adverse events, with severity determined according to the U.S. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAEv5.0)

Trial Locations

Locations (8)

GuiZhou Provincial People's Hospital; 🇨🇳 Guiyang, China

Cancer Hospital of Shantou University Medical College; 🇨🇳 Shantou, Guangdong, China

Chongqing University cancer hospital; 🇨🇳 Chongqing, Chongqing, China

Shandong Provincial Hospital; 🇨🇳 Jinan, Shandong, China

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China

China West Hospital; 🇨🇳 Chengdu, Sichuan, China

LiaoNing Cancer Hospital & Institute; 🇨🇳 Shenyang, Liaoning, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China