Immunotherapy Combined with Hypofractionated Concurrent Chemoradiotherapy Followed by Immunotherapy in LA-NSCLC

NCT06849167 | Recruiting Phase 2 DMC

• 1 other identifier: LGH2024453
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with locally advanced NSCLC (Non-Small Cell Lung Cancer) who have a PD-L1 TPS ≥ 20% will be included in this study. It aims to explore the efficacy and safety of immunotherapy combined with hypofractionated concurrent chemoradiotherapy, followed by consolidation immunotherapy. Participants will undergo large fractionated radiotherapy with a total dose of 48Gy/16 fractions, 3Gy per fraction, 5 days a week. Participants will receive two cycles of concurrent platinum-based doublet chemotherapy and concurrent immunotherapy. Patients without progression will receive consolidation immunotherapy. The maximum duration of immunotherapy is 24 months.

Conditions

Non-Small Cell Lung Cancer

Keywords

Immunotherapy; Non-Small Cell Lung Cancer; hypofractionated radiotherapy

Outcome Measures

Primary Outcomes (1)

• PFS

  From subject enrollment to the first recorded disease progression or death from any cause, whichever occurs first

  through study completion, an average of 3 years

Secondary Outcomes (7)

• ORR

  through study completion, an average of 3 years

• DCR

  through study completion, an average of 3 years

• DOR

  through study completion, an average of 3 years

• OS

  through study completion, an average of 3 years

• HRQoL Assessment:

  through study completion, an average of 3 years

Study Arms (1)

hypofractionated group

EXPERIMENTAL

Immunotherapy combined with hypofractionated concurrent chemoradiotherapy followed by consolidation immunotherapy

Radiation: hypofractionated radiotherapy with immunotherapy

Interventions

hypofractionated radiotherapy with immunotherapy RADIATION

Immunotherapy combined with hypofractionated concurrent chemoradiotherapy followed by consolidation immunotherapy

hypofractionated group

Eligibility Criteria

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

You may qualify if:

• Sign a written informed consent before implementing any trial-related procedures.
• Age ≥ 18 years and ≤ 70 years, male or female.
• Histologically or cytologically confirmed inoperable locally advanced (IIB-IIIC) NSCLC (International Association for the Study of Lung Cancer and American Joint Committee on Cancer 8th edition TNM lung cancer staging);
• Notes:
• If EBUS/EUS or mediastinoscopy can safely obtain samples from the hilar or mediastinal lymph nodes, it is encouraged to obtain tissue for confirmation of involvement. When the lymph node boundary is clear and at least one lymph node has a short axis ≥ 2.0 cm, lymph node involvement can be determined by imaging (CT/MRI scan). For lymph nodes with a short axis \< 2.0 cm, if pathologically confirmed, the patient can be included in the study. If the primary tumor is deemed unresectable and mediastinal lymph node metastasis does not affect the radiotherapy plan, the patient can be included.
• Determined and documented by a multidisciplinary tumor board or consultation with a thoracic surgeon: the patient has inoperable stage IIB-IIIC NSCLC.
• No evidence of distant metastatic disease on diagnostic quality CT or MRI scans of the chest, abdomen, pelvis, and brain and/or whole-body fluorodeoxyglucose (FDG)-PET/CT, and classified as non-IV stage NSCLC (i.e., M0).

You may not qualify if:

• Provide a sufficient amount of quality-controlled tumor tissue or cell wax blocks for the pathology department of the study center to test PD-L1 expression using the 22C3 antibody, with a PD-L1 TPS ≥ 20%; or a pre-screening PD-L1 TPS ≥ 20% result (regardless of the antibody used, including 22C3, SP263, SP142).
• At least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for use as a target lesion.
• No prior treatment for advanced/metastatic NSCLC (chemotherapy, targeted therapy, immunotherapy, or radiotherapy). Patients who have previously received systemic induction or neoadjuvant therapy (chemotherapy, immunotherapy) for stage IIB-IIIC NSCLC and are about to receive curative concurrent chemoradiotherapy can be included in the study.
• Patients who have previously received induction immunotherapy can be included, including the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or drugs targeting another co-stimulatory or inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137), immune LAG-3 inhibitors, and TIGIT monoclonal antibodies.
• ECOG performance status of 0-1.
• Life expectancy ≥ 6 months.
• Adequate organ function, with the following laboratory parameters:
• For women of childbearing potential, a negative urine or serum pregnancy test must be performed within 3 days prior to the first dose of study drug (Day 1 of Cycle 1). If the urine pregnancy test cannot be confirmed as negative, a serum pregnancy test is required. Non-childbearing potential women are defined as those who are at least 1 year post-menopausal, surgically sterilized, or have undergone a hysterectomy.
• If there is a risk of pregnancy, all participants (regardless of sex) must use a contraceptive method with a failure rate of less than 1% during the entire treatment period and for 120 days after the last dose of the study drug (or 180 days after the last dose of chemotherapy).
• Pathologically diagnosed small cell lung cancer (SCLC), or mixed tumors containing small cell components.
• Have undergone genetic testing prior to enrollment and known to have sensitive mutations in EGFR, ALK, or ROS-1 genes.
• Subjects evaluated by the investigator with cavitary squamous carcinoma or imaging suggesting large vessel invasion/infiltration, or those with a history of active hemoptysis (coughing up at least 1/2 teaspoon of fresh blood) within 2 weeks prior to the first dose of the study drug.
• In the planned radiotherapy regimen, the volume of normal lung tissue (total lung - GTV) receiving a total radiation dose \>20Gy may exceed 34%.
• Have previously received any chest-directed radiotherapy (including esophagus, mediastinum, or breast cancer radiotherapy) before the first dose of the study drug.
• Have undergone major surgery within 3 weeks prior to the first dose of the study drug (excluding surgeries for biopsy purposes or vascular access placement, but subjects must have fully recovered from treatment toxicities and/or complications).

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (1)

Peking University Cancer Hospital & Institute

Beijing, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Immunotherapy

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)

Immunomodulation; Biological Therapy; Therapeutics

Central Study Contacts

Huiming Yu

CONTACT

010-8819 6984; huiming740512@126.com

Yue Teng

CONTACT

86-15910501617; tengyue1116@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Peking University Cancer Hospital & Institute (PekingUCHI)

Study Record Dates

• First Submitted: February 17, 2025
• First Posted: February 27, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2030
• Last Updated: February 27, 2025

Record last verified: 2025-02

Locations

CN (1)