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

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

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

Study Overview

• Status: Completed
• Conditions: Relapsed Small Cell Lung Cancer
• Intervention / Treatment: Drug: CS1001

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chendu, Sichuan, China, 610041
      • West China Hospital, Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low-dose radiation+CS1001	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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.
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.
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.

Collaborators and Investigators

• Sponsor: CStone Pharmaceuticals
• Investigators: Principal Investigator: You Lu, MD, West China Hospital

Publications and helpful links

General Publications

• 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 Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. doi: 10.1056/NEJMoa1809064. Epub 2018 Sep 25.
• 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;14(2):237-244. doi: 10.1016/j.jtho.2018.10.003. Epub 2018 Oct 10.
• 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.
• 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, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. doi: 10.1016/S0140-6736(19)32222-6. Epub 2019 Oct 4.
• 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 Radiation Therapy and Anti-PD1 in Mice and Patients With Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2020 Sep 1;108(1):212-224. doi: 10.1016/j.ijrobp.2020.05.002. Epub 2020 May 15.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2021
• Primary Completion (Actual): December 22, 2023
• Study Completion (Actual): December 22, 2023

Study Registration Dates

• First Submitted: May 29, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: CS1001-101-13

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes