Safety and Tolerability Evaluation of Low-dose Radiation in Combination With CS1001 in Relapsed SCLC Patients

Relapsed Small Cell Lung Cancer Clinical Trial

Official title:

A Phase Ia/Ib, Open-Label, Multiple-Dose, Dose-Escalation and Expansion Study of the Anti-PD-L1 Monoclonal Antibody CS1001 in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04421352
• Other study ID #: CS1001-101-13
• Status: Completed
• Phase: Phase 1
• Start date: January 12, 2021
• Est. completion date: December 22, 2023

Study information

• Verified date: March 2024
• Source: CStone Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase Ia/Ib Safety and Tolerability Evaluation of Low-dose Radiation in Combination with CS1001 in relapsed SCLC patients

Description:

This is a dose-escalation study of Low-dose Radiation in combination with CS1001 in relapsed SCLC patients. Patients are assigned to 3 treatment groups received from 3 Gy to 15Gy, to determine the safety, tolerability and the maximal tolerant dose. Biomarkers and immunological markers are collected and analyzed as well.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: December 22, 2023
• Est. primary completion date: December 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Patients with histologically or cytologically confirmed LS-SCLC or ES-SCLC and experienced progression since first-line standard platinum containing dual-drug chemotherapy.

2. Patients whose initial diagnosis was limited must undergo radical chest radiotherapy and the time of tumor progression is not less than 3 months from the end of radiotherapy, or cannot receive radical chest radiotherapy due to specific reasons

3. At least one extracranial measurable lesion (RECIST v1.1), and for a lesion that has received radiotherapy, progression of the lesion after radiotherapy must be confirmed.

4. Patients with brain metastases are allowed to receive previous radiotherapy and their condition is stable, but the time to the end of radiotherapy must not be less than 3 months.

5. No radiotherapy contraindications were judged by the radiologist

6. ECOG performance status of 0 or 1.

7. Patients with life expectancy = 3 months.

8. Patients must have adequate organ function.

9. Fertile men and women of childbearing potential must agree to use an effective method of birth control from providing signed consent and for 6 months after last study drug administration.

Exclusion Criteria:

1. Subjects known to have primary CNS tumors or meningeal metastases or unstable CNS metastases.

2. Patients with active autoimmune diseases or history of autoimmune diseases should be excluded.

3. Patients who have received immune checkpoint proteins/antibody/medicine (including PD-1, PD-L1, etc) for treatment.

4. Known history of HIV infection.

5. Subjects with active chronic hepatitis B or active hepatitis C .

6. Patients who have serious hypersensitive reaction to monoclonal antibodies, and have history of uncontrolled allergic asthma.

7. Known history of alcoholism or drugs abuse.

8. Subjects with history of radiation pneumonitis of grade 3 or above, regardless of recovered or not.

Related Conditions & MeSH terms

• Relapsed Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• CS1001
low-dose radiation+CS1001 1200mg Q3W. In the dose escalation part, the dose levels will be escalated following a modified 3+3 dose escalation scheme. Dose A: 3Gy/1f; Dose B: 9Gy/3f; Dose C: 15Gy/5f; In the dose expansion part, more SCLC patients will be assigned.

Locations

Country	Name	City	State
China	West China Hospital, Sichuan University	Chendu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
CStone Pharmaceuticals

Country where clinical trial is conducted

China, 

References & Publications (5)

Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-Line At — View Citation

Li LY, Wang H, Chen X, Li WQ, Cui JW. First-line atezolizumab plus chemotherapy in treatment of extensive small cell lung cancer: a cost-effectiveness analysis from China. Chin Med J (Engl). 2019 Dec 5;132(23):2790-2794. doi: 10.1097/CM9.0000000000000536. — View Citation

Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H — View Citation

Ready N, Farago AF, de Braud F, Atmaca A, Hellmann MD, Schneider JG, Spigel DR, Moreno V, Chau I, Hann CL, Eder JP, Steele NL, Pieters A, Fairchild J, Antonia SJ. Third-Line Nivolumab Monotherapy in Recurrent SCLC: CheckMate 032. J Thorac Oncol. 2019 Feb; — View Citation

Yin L, Xue J, Li R, Zhou L, Deng L, Chen L, Zhang Y, Li Y, Zhang X, Xiu W, Tong R, Gong Y, Huang M, Xu Y, Zhu J, Yu M, Li M, Lan J, Wang J, Mo X, Wei Y, Niedermann G, Lu Y. Effect of Low-Dose Radiation Therapy on Abscopal Responses to Hypofractionated Rad — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the recommended radiation dose and preliminarily evaluate the anti-tumor efficacy of CS1001 in combination with low-dose radiotherapy in subjects with limited or extensive stage SCLC who failed the firstline treatment		From date of the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.
Secondary	Incidence of Adverse Events (AE) and Dose-Limiting Toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V4.03		From first dose to 30 days after last dose of CS1001, up to 2 years.
Secondary	Cmax: Peak concentration, the maximum drug concentration measured during one dosing cycle		From first dose to 30 days after last dose of CS1001, up to 2 years.
Secondary	The number and percentage of subjects with detectable Anti-drug Antibody (ADA)		From first dose to 30 days after last dose of CS1001, up to 2 years.