Phase II Trial of SFRT Plus Chemo-immunotherapy for LA-NSCLC With Suboptimal Neoadjuvant Response

NCT07670715 | Not Yet Recruiting Phase 2

• 1 other identifier: E20260711
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Lattice radiation therapy (LRT) is a spatially fractionated thoracic radiotherapy technique that creates alternating high- and low-dose regions within primary lung tumors and metastatic lymph nodes to strengthen local tumor suppression and reduce radiation injury to normal thoracic organs. This study aims to evaluate the efficacy and safety of combining LRT with consolidation chemoimmunotherapy in unresectable stage III LA-NSCLC patients who show suboptimal tumor response to prior neoadjuvant chemoimmunotherapy, through a single-arm Phase II clinical trial. Patients will receive thoracic LRT delivered by a medical linear accelerator. High-dose spherical sub-targets will be contoured within the gross tumor volume of primary lung lesions and regional nodal metastases under standardized dose constraints to spare the lung, heart and esophagus. All enrolled subjects will receive sequential consolidation chemoimmunotherapy administered within one week after finishing LRT. Tumor response, treatment-related adverse events, local tumor control and long-term survival outcomes will be prospectively tracked throughout treatment and long-term follow-up.

Conditions

Locally Advanced Non-small Cell Lung Cancer (NSCLC); Thoracic Radiotherapy; Immune Checkpoint Inhibitors; Neoadjuvant Chemoimmunotherapy

Keywords

spatially fractionated radiotherapy; Locally Advanced NSCLC; Neoadjuvant Chemoimmunotherapy

Outcome Measures

Primary Outcomes (2)

• Objective response rate

  Objective response rate (ORR) assessed by RECIST version 1.1, calculated as the proportion of patients achieving complete response (CR) or partial response (PR) after combination therapy. Tumor lesions will be evaluated with contrast-enhanced CT scans of chest, abdomen and pelvis.

  From enrollment up to 12 months after the last subject completes combination therapy

• Pathological complete response

  The proportion of patients achieving pathological complete response (pCR), defined as absence of viable residual tumor cells in post-treatment surgical resection specimens.

  From enrollment to 12 months after the last subject completes all study combination therapy

Secondary Outcomes (4)

• Major pathological response

  From enrollment up to 12 months after the last subject completes combination therapy

• R0 resection rate

  From enrollment up to 12 months after the last subject completes combination therapy

• Event-free survival

  From enrollment up to 24 months after the last subject completes study treatment

• Incidence of treatment-related adverse events

  From enrollment through 30 days after completion of all study treatment

Study Arms (1)

experimental group

EXPERIMENTAL

Eligible patients with unresectable stage III LA-NSCLC who achieved suboptimal tumor response after prior neoadjuvant chemoimmunotherapy in this Phase II trial will receive thoracic lattice radiation therapy using a medical linear accelerator. Within the gross tumor volume (GTV) of primary lung lesions and metastatic regional lymph nodes, spherical high-dose LRT sub-targets will be delineated with fixed diameter and inter-target spacing standards. The LRT sub-targets must be contoured fully within the GTV, spare vital intrathoracic vessels, maintain a minimum safety margin from the outer GTV border, and account for a regulated volume percentage of the whole GTV. For thoracic tumor lesions, the D95 coverage of total GTV and individual LRT high-dose targets will follow defined per-fraction dose limits, while all efforts will be made to lower single-fraction radiation burden to lung, heart and esophagus organs at risk. After finishing the full course of lattice radiotherapy, standardized

Radiation: lattice radiation therapy

Interventions

lattice radiation therapy RADIATION

Eligible stage III unresectable LA-NSCLC patients with suboptimal neoadjuvant response receive thoracic lattice radiotherapy via linear accelerator. Spherical high-dose LRT sub-targets are contoured inside primary and nodal GTV, avoiding blood vessels with 1cm margin and 1%-10% volume ratio of GTV. Standard fractional dose constraints for GTV and LRT targets are followed, with minimal radiation to heart, lung and esophagus. Brain and bone metastases get separate palliative radiotherapy, not included in thoracic LRT plan. Consolidation chemoimmunotherapy will be initiated within one week after radiotherapy completion.

experimental group

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed unresectable stage III locally advanced non-small cell lung cancer (LA-NSCLC).
• Received at least 2 cycles of standard neoadjuvant chemoimmunotherapy, with suboptimal tumor response verified by post-induction radiological evaluation.
• Age ≥ 18 years old.
• ECOG performance status of 0 or 1.
• Adequate hematologic, hepatic and renal function to complete radiotherapy and consolidation systemic therapy.
• Voluntarily sign written informed consent and be capable of following study-related procedures.

You may not qualify if:

• Prior thoracic radiotherapy history.
• Active uncontrolled autoimmune disorders or persistent severe immune-related adverse events.
• Untreated symptomatic brain metastases.
• Severe irreversible cardiac, pulmonary, liver or renal dysfunction that cannot tolerate combined radiotherapy and immunotherapy.
• Pregnant or breastfeeding women.
• Concurrent or previous other malignant tumors within 5 years, except cured basal cell skin cancer and cervical carcinoma in situ.
• Any absolute contraindication to lattice radiation therapy or immune checkpoint inhibitor.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300000, China

Location

Central Study Contacts

Ningbo Liu, Doctor

CONTACT

+8615602036608; liuningbo@tjmuch.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: June 26, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: June 26, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)