NCT04245514

Multimodality Treatment in Stage III Non-small Cell Lung Cancer (NSCLC)

Immune-modulatory Radiotherapy to Enhance the Effects of Neoadjuvant PD-L1 Blockade After Neoadjuvant Chemotherapy in Patients With Resectable Stage III(N2) Non-small Cell Lung Cancer (NSCLC): A Multicenter Phase II Trial

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: Swiss Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Resectable, locally advanced NSCLC with involvement of mediastinal lymph nodes (N2) is associated with a high risk of (systemic) recurrence despite neo-adjuvant chemotherapy. Neo-adjuvant immunotherapy is a promising additional treatment modality aiming at increasing local control and better tackling micrometastases at the time of radical local treatment. Radiotherapy is thought to act synergistically with immunotherapy through release of tumor antigens and modulation of the local immune microenvironment in favor of a better antigen-presentation and (systemic) anti-tumor immune response (abscopal effect). The aim of the proposed SAKK 16/18 trial is to evaluate the efficacy and safety of adding immune-modulatory radiotherapy to the SAKK 16/14 treatment regimen by combining neo-adjuvant radio-immunotherapy. Due to the lack of evidence for an optimal radiotherapy regimen for an "in-situ vaccination" effect three different radiotherapy regimens will be tested.

Detailed description

In resectable locally advanced lung cancer there is an urgent need for more efficacious therapy, since most of the patients will eventually have a relapse and will die of the disease. Distant metastases are the main site of recurrence. Therefore, the most promising treatment strategy is to better eliminate micrometastases present at the time of diagnosis through improved systemic treatment. In this regard, the SAKK 16/14 trial is investigating the efficacy of the anti-PD-L1 inhibitor durvalumab before and after surgery added to standard neoadjuvant chemotherapy with cisplatin/docetaxel. It has just completed accrual as of Q1 2019. The primary aim of the SAKK 16/18 trial is to evaluate the efficacy and safety of adding immune-modulatory radiotherapy to the SAKK 16/14 treatment regimen by combining it with neoadjuvant immunotherapy. Due to the lack of evidence for an optimal immune-modulatory radiotherapy regimen we test 3 different radiotherapy regimens to investigate differences in efficacy and tolerability as key exploratory endpoint. Neoadjuvant therapy is the optimal setting to test the combination of immune-modulatory radiotherapy and immune checkpoint inhibitor therapy. Resection of the primary tumor and mediastinal lymph nodes will allow to investigate pathological responses and nodal downstaging at an early time point. Furthermore, this setting allows for extensive translational research evaluating cellular and molecular mechanisms of anti-tumor immune response. SAKK 16/18 is a prospective, multicenter, phase II trial with 3 radiotherapy cohorts. The treatment consists of * Neoadjuvant chemotherapy with cisplatin and docetaxel: 3 cycles of 21 days * Neoadjuvant immunotherapy with durvalumab: 1 cycle * Neoadjuvant immune-modulatory radiotherapy * Concurrent with neoadjuvant immunotherapy * Random assignment to one of the following fractionation regimens: * 20x2 Gy (weekdaily, 4 weeks) * 5x5 Gy (weekdaily, 1 week) * 3x8 Gy (on alternate days, 1 week) * Surgery o Between 4 and 6 weeks after the application of durvalumab (independent of the radiotherapy regimen) * If indicated: Postoperative radiotherapy (should start between 3 to 6 weeks after surgery) * Adjuvant immunotherapy with durvalumab: 13 cycles of 28 days

Conditions

• Non-small Cell Lung Cancer
• NSCLC

Interventions

Type	Name	Description
DRUG	Durvalumab	Immunotherapy
RADIATION	Radiotherapy	Immune-modulatory radiotherapy to the primary tumor, with either Cohort A: 20 x 2 Gy weekdaily Cohort B: 5 x 5 Gy weekdaily Cohort C: 3 x 8 Gy q2d

Timeline

• Start date: 2020-07-15
• Primary completion: 2026-07-16
• Completion: 2031-12-01
• First posted: 2020-01-29
• Last updated: 2026-04-02

Locations

13 sites across 2 countries: Germany, Switzerland