Phase II Trial: Low-Dose Radiation + SBRT + Sintilimab + Chemotherapy vs. Sintilimab + Chemotherapy in Locally Advanced or Metastatic Squamous Cell Lung Cancer

Official title

Low-dose Radiation Therapy and Stereotactic Body Radiation Therapy Combined With PD-1 Inhibitor Sintilimab and Chemotherapy Versus PD-1 Inhibitor Combined With Chemotherapy as First-line Treatment for Patients With Locally Advanced or Metastatic Squamous Cell Lung Cancer: A Randomized, Phase II Multicenter Clinical Trial

Overview

This is a randomized, controlled, open-label, multicenter phase II clinical trial comparing the efficacy and safety of low-dose radiation therapy and stereotactic body radiation therapy combined with PD-1 inhibitor (sintilimab) and standard platinum-based doublet chemotherapy versus PD-1 inhibitor (sintilimab) combined with standard platinum-based doublet chemotherapy as first-line treatment in patients with locally advanced or metastatic squamous cell lung cancer. There will be 57 subjects in the experimental group and 57 subjects in the control group, with a total of 114 subjects.

Detailed description

This is a randomized, controlled, open-label, multicenter phase II clinical trial comparing the efficacy and safety of low-dose radiation therapy and stereotactic body radiation therapy combined with PD-1 inhibitor (sintilimab) and standard platinum-based doublet chemotherapy versus PD-1 inhibitor (sintilimab) combined with standard platinum-based doublet chemotherapy as first-line treatment in patients with locally advanced or metastatic squamous cell lung cancer. Patients with previously untreated, locally advanced or metastatic (unresectable or not eligible for definitive chemoradiotherapy, stage IIIB-IV) squamous cell lung cancer who have signed informed consent will be screened for eligibility. Qualified subjects who meet the inclusion criteria will be randomly assigned at a 1:1 ratio to the experimental group (radiation therapy plus sintilimab and chemotherapy) or the control group (sintilimab plus chemotherapy). Based on sample size estimation according to statistical hypotheses, there will be 57 subjects in the experimental group and 57 subjects in the control group, with a total of 114 subjects. Subjects in the experimental group will receive radiation therapy. Within 1 week after radiation therapy, they will receive treatment with sintilimab combined with standard platinum-based doublet chemotherapy. Chemotherapy combined with immunotherapy will consist of a total of 4 cycles. Patients will subsequently receive maintenance therapy with sintilimab. Subjects in the control group will receive treatment with sintilimab combined with standard platinum-based doublet chemotherapy, consisting of a total of 4 cycles. Patients will subsequently receive maintenance therapy with sintilimab. The primary efficacy endpoint of this study is objective response rate (ORR), as assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

Interventions

• Radiation low-dose radiation therapy and stereotactic body radiation therapy
  Patients will receive radiation therapy.
• Drug chemotherapy
  Patients will receive sintilimab combined with standard platinum-based doublet chemotherapy for a total of 4 cycles. Patients subsequently received maintenance treatment with sintilimab, and continued treatment until disease progression (PD), intolerable toxicity, withdrawal of informed consent, initiation of other anti-tumor treatments, death, or other circumstances that should stop treatment as specified in the protocol. Whichever occurs first. The maximum treatment time with sintilimab is 24
• Drug Sintilimab
  Patients will receive sintilimab combined with standard platinum-based doublet chemotherapy for a total of 4 cycles. Patients subsequently received maintenance treatment with sintilimab, and continued treatment until disease progression (PD), intolerable toxicity, withdrawal of informed consent, initiation of other anti-tumor treatments, death, or other circumstances that should stop treatment as specified in the protocol. Whichever occurs first. The maximum treatment time with sintilimab is 24

Primary outcome measures

• objective response rate (ORR) [Time frame: Every 6 weeks (±7 days) from the first dose of study drug, and every 12 weeks (±7 days) after 48 weeks (up to 24 months).]

Secondary outcome measures (4)

• 6-month PFS rate [Time frame: From date of randomization to 6 months.]
• 1-year PFS rate [Time frame: From date of randomization to 1 years.]
• overall survival(OS) [Time frame: From date of randomization to the time when the subject died from any cause, assessed up to 36 months.]
• Progression-free survival (PFS) [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years old and ≤ 75 years old;
• Histologically or cytologically confirmed squamous cell lung cancer, imaging confirmed locally advanced or metastatic disease (unresectable or not eligible for definitive chemoradiotherapy, stage IIIB-IV);
• According to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), there is at least one imaging measurable lesion;
• Enough to provide quality control qualified tumor tissue or cell wax blocks to detect PD-L1 expression;
• Have not received any systemic anti-tumor treatment for locally advanced or metastatic disease in the past;

Exclusion criteria

• The pathology is small cell lung cancer (SCLC), including lung cancer mixed with SCLC and non-small cell lung cancer (NSCLC)；
• The pathology is lung adenocarcinoma, including lung cancer mixed with lung adenocarcinoma and lung squamous cell carcinoma;
• EGFR gene sensitive mutation or ALK fusion positive or ROS1 fusion positive;
• Previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or another drug that stimulates or synergistically inhibits T cell receptors;
• Pregnant or lactating women;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 6 centers

• The Second Affiliated Hospital of Chongqing Medical University — Chongqing
• Guizhou Provincial People's Hospital — Guiyang
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan
• Sichuan Cancer Hospital — Chengdu
• West China Hospital of Sichuan University — Chengdu
• Affiliated Hospital of North Sichuan Medical College — Nanchong

Publications

• Zhang R, Chen M, Yin N, Xue J. Low-dose radiation and stereotactic body radiotherapy with PD-1 inhibitor sintilimab and chemotherapy for first-line treatment of locally advanced or metastatic squamous lung cancer: protocol for a randomised phase II trial (IHC002 study). BMJ Open. 2025 Aug 31;15(8):e094859. doi: 10.1136/bmjopen-2024-094859. PMID 40887121

Identifiers

NCT: NCT06121505 · IHC-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗