Safety and Tolerability Evaluation of Sintilimab in Combination With Radiation in Stage IV NSCLC Patients

NCT03812549 | Completed Phase 1 Results DMC

• 1 other identifier: IHC-001
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase I trial aims to investigate the safety and tolerability of anti-programmed cell death-1 (PD-1) monoclonal antibody Sintilimab (also called IBI308) in combination with concurrent stereotactic body radiation therapy (SBRT) and low dose radiotherapy (LDRT) in treating patients with stage IV non-small cell lung cancer (NSCLC). At least 29 participants will be enrolled in this study. All will take part at West China Hospital, Sichuan University.

Conditions

Stage IV NSCLC

Keywords

Immunotherapy;SBRT; PD-L1 positive; LDRT

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events and/or Dose Limiting Toxicities of Sintilimab in Combination With SBRT and LDRT

  Adverse Events and/or Dose Limiting Toxicity graded per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  from randomization through 30 days after last dosing, up to 24 months

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  up to 24 months after the enrollment

• Objective Response Rate (ORR)

  up to 24 months after the enrollment

• Overall Survival (OS)

  up to 24 months after the enrollment

Study Arms (1)

Sintilimab Combined with SBRT and LDRT

EXPERIMENTAL

Period 1-Dose escalation cohort. Dose Level 1: Stereotactic body radiation therapy (SBRT) dose at 30 Gy/3f + Low Dose Radiotherapy (LDRT, 2 Gy in 1 fraction) + anti-PD-1 inhibitor 200mg. Dose Level 2: Stereotactic body radiation therapy (SBRT) dose at 30 Gy/3f + Low Dose Radiotherapy (LDRT, 4 Gy in 2 fractions) + anti-PD-1 inhibitor 200mg. Dose Level 3: Stereotactic body radiation therapy (SBRT) dose at 30 Gy/3f + Low Dose Radiotherapy (LDRT, 10 Gy in 5 fractions) + anti-PD-1 inhibitor 200mg. Period 2 - Expansion cohort. SBRT dose at 30 Gy/3f + LDRT + anti-PD-1 inhibitor 200mg, LDRT dose at RDE determined in Period 1.

Drug: Sintilimab; Radiation: stereotactic body radiation therapy; Radiation: Low Dose Radiotherapy

Interventions

Sintilimab DRUG

Patients will receive treatment with Sintilimab 200mg every 3 weeks for a maximum of 24 months.

Also known as: IBI308

Sintilimab Combined with SBRT and LDRT

stereotactic body radiation therapy RADIATION

Radiation treatment utilized in this trial consists of SBRT with a standard doses to 30 Gy/3f

Also known as: SBRT

Sintilimab Combined with SBRT and LDRT

Low Dose Radiotherapy RADIATION

LDRT at dose escalation levels: 2 Gy/1f, 4 Gy/2f, 10 Gy/5f with conventional external beam radiation.

Also known as: LDRT

Sintilimab Combined with SBRT and LDRT

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically or cytologically confirmed stage IV NSCLC.
• Enough tumor tissue samples.
• No previous radiation, chemotherapy, immunotherapy. Patients who have received neoadjuvant or adjuvant chemotherapy 12 months before enrollment is permitted.
• At least three measurable disease according to RECIST 1.1 that meet SBRT and LDRT radiation requirement as protocol defined
• PD-L1 expression positive (TPS \>1%)
• Be ≥18 years of age on day of signing informed consent and ≤75 years old.
• ECOG 0-1.
• Patients must have normal organ and marrow function as defined below: Total bilirubin \</= 1.5 mg/dL. Aminotransferase (AST) Serum Glutamic Oxaloacetic Transaminase (SGOT)/ Alanine Aminotransferase (ALT) Serum Glutamic-Pyruvic Transaminase (SGPT) \<2.5 X institutional upper limit of normal (patients with liver involvement will be allowed \</= 5.0 X institutional upper normal limit) \*WBC \>/= 3500/uL, ANC \>/= 1500/uL \*Platelets \>/= 90K \*Hemoglobin \>/= 9g/dL \*Creatinine \</= 1.5 x ULN.
• Be willing and able to provide written informed consent/assent for the trial.
• Patients should be able to tolerate a course of radiotherapy as assessed by the investigator.
• No contradiction to radiation per radio-oncologists' judgments
• Life expectancy of \> 6 months.

You may not qualify if:

• EGFR/ALK/ROS-1 mutation or mutation status unknown.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Subjects with coronary bypass operation.
• Subjects with insufficient heart function, liver function and kidney function.
• Subjects with severe uncontrollable psychotic symptoms.
• Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor agents) within 4 weeks prior to enrollment or anticipated requirement for systemic immunosuppressive medications during the trial.
• Subjects with active, known or suspected autoimmune disease such as interstitial pneumonia, uveitis, Crohn's disease, autoimmune thyroiditis. Subjects with cured childhood asthma, type I diabetes mellitus only requiring hormone replacement.
• Known history of allogeneic organ or allogeneic hemopoietic stem cell transplantation.
• Known hypersensitivity or allergy to monoclonal antibody.
• Subjects with a history of interstitial lung disease.
• Uncontrolled concomitant disease, including but not limited to :
• )Active or poorly controlled severe infection 2)Human Immunodeficiency Virus (HIV) infection (HIV antibody positive) 3)Known acute or chronic active hepatitis B (HBV DNA positive) infection or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive) infection 4)Active tuberculosis 5)Symptomatic congestive heart failure (New York Heart Association grade III-IV) or symptomatic, poorly controlled arrhythmia 6)Uncontrolled hypertension (SBP ≥ 160mmHg or DBP ≥ 100mmHg) 7)Prior arterial thromboembolism event, including myocardial infarction, unstable angina, stroke and transient ischemic attack, within 6 months of enrollment 8)Concomitant disease needs anticoagulant therapy 9)Uncontrolled hypercalcemia（Ca2+\>1.5mmol/L or Ca \>12mg/dl or corrected Serum Calcium \>ULN），or Symptomatic hypercalcemia during diphosphonate therapy
• \. Other primary malignancy, with the exception of: (radical Non-melanoma skin cancer or cured cervical in-situ carcinoma;).
• \. Subjects with other diseases or abnormal Lab test results which might increase the risk of enrollment and treatment or Interfere with the interpretation of study results could be excluded according to the judgments of investigator.
• \. Pregnant or lactating women.

Sponsors & Collaborators

• Sichuan University: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Related Publications (8)

• Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015 Apr 3;348(6230):56-61. doi: 10.1126/science.aaa8172.

  PMID: 25838373 BACKGROUND

• Demaria S, Coleman CN, Formenti SC. Radiotherapy: Changing the Game in Immunotherapy. Trends Cancer. 2016 Jun;2(6):286-294. doi: 10.1016/j.trecan.2016.05.002.

  PMID: 27774519 BACKGROUND

• Kaur P, Asea A. Radiation-induced effects and the immune system in cancer. Front Oncol. 2012 Dec 17;2:191. doi: 10.3389/fonc.2012.00191. eCollection 2012.

  PMID: 23251903 BACKGROUND

• Bernstein MB, Krishnan S, Hodge JW, Chang JY. Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach? Nat Rev Clin Oncol. 2016 Aug;13(8):516-24. doi: 10.1038/nrclinonc.2016.30. Epub 2016 Mar 8.

  PMID: 26951040 BACKGROUND

• Park SS, Dong H, Liu X, Harrington SM, Krco CJ, Grams MP, Mansfield AS, Furutani KM, Olivier KR, Kwon ED. PD-1 Restrains Radiotherapy-Induced Abscopal Effect. Cancer Immunol Res. 2015 Jun;3(6):610-9. doi: 10.1158/2326-6066.CIR-14-0138. Epub 2015 Feb 19.

  PMID: 25701325 BACKGROUND

• Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, Rasalan T, Adamow M, Ritter E, Sedrak C, Jungbluth AA, Chua R, Yang AS, Roman RA, Rosner S, Benson B, Allison JP, Lesokhin AM, Gnjatic S, Wolchok JD. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012 Mar 8;366(10):925-31. doi: 10.1056/NEJMoa1112824.

  PMID: 22397654 BACKGROUND

• Du J, Su S, Li H, Shao J, Meng F, Yang M, Qian H, Zou Z, Qian X, Liu B. Low dose irradiation increases adoptive cytotoxic T lymphocyte migration in gastric cancer. Exp Ther Med. 2017 Dec;14(6):5711-5716. doi: 10.3892/etm.2017.5305. Epub 2017 Oct 13.

  PMID: 29285113 BACKGROUND

• Brooks ED, Chang JY. Time to abandon single-site irradiation for inducing abscopal effects. Nat Rev Clin Oncol. 2019 Feb;16(2):123-135. doi: 10.1038/s41571-018-0119-7.

  PMID: 30401936 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

sintilimab; Radiosurgery; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Prof. You Lu
• Organization: West China Hospital, Sichuan University

radyoulu@hotmail.com

13398179653

Study Officials

• You Lu, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of Department of Thoracic Oncology

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: January 23, 2019
• Study Start: January 18, 2019
• Primary Completion: January 31, 2022
• Study Completion: July 8, 2022
• Last Updated: March 4, 2025
• Results First Posted: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)