Neoadjuvant Immunotherapy With Durvalumab (MEDI4736) in Non-Surgical Early Stage or Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Followed by Radical Radiotherapy or Chemoradiotherapy

Phase 1

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: Durvalumab; Other: standard of care RT/RCT

• Registration Number: NCT05267392
• Lead Sponsor: Instituto Portugues de Oncologia, Francisco Gentil, Porto

Brief Summary

This study proposes to evaluate the safety and efficacy of an anti-PD-L1 (durvalumab) agent as neoadjuvant therapy in patients diagnosed with localized NSCLC who are planned to undergo radical RT or CRT. The hypothesis to be tested for the primary objective is that the treatment of durvalumab followed by RT/CRT will be safe and well tolerated in subjects with NSCLC.

Detailed Description

Targeting the PD1/PD-L1 pathway has demonstrated activity in patients with several advanced malignancies. Treatment with anti-PD1/PD-L1 blockade in advanced and, more recently, locally advanced NSCLC, is already standard of care. The positive outcomes of durvalumab following CRT emphasized the potential of immunotherapy integration in multimodality treatment strategies and in earlier phases of the disease, leading to the first immune checkpoint inhibitor approval in non-metastatic setting in NSCLC. Furthermore, growing evidence is pointing to the efficacy of neoadjuvant treatments in NSCLC. This study proposes to evaluate the safety and efficacy of an anti-PD-L1 (durvalumab) agent as neoadjuvant therapy in patients diagnosed with localized NSCLC who are planned to undergo radical RT or CRT.

The hypothesis to be tested for:

* Primary objective: To evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of durvalumab followed by RT/CRT in patients with early stage or locally advanced, unresectable NSCLC who are planned to undergo radical RT or CRT.

* Secondary Objectives: To evaluate the safety, the efficacy and the feasibility of durvalumab followed by RT/CRT.

* Exploratory Objectives: To assess the Quality of Life (QoL) using SF-36v2 and EQ-5D-5L and to assess blood and tumor tissue for potential biomarkers which predict and/or correlate with clinical outcomes.

Study Timeline

• Study Start: 2021-02-16
• Status Verified: 2021-12
• Study First Submitted: 2021-12-13
• Study First Submitted QC: 2022-02-23
• Last Update Submitted: 2022-02-23
• Study First Posted: 2022-03-04
• Last Update Posted: 2022-03-04
• Primary Completion: 2023-07
• Study Completion: 2024-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Durvalumab	standard of care RT/RCT	All subjects enrolled in the study will receive open-label neoadjuvant durvalumab 1500 mg followed by standard of care RT/RCT
Durvalumab	Durvalumab	All subjects enrolled in the study will receive open-label neoadjuvant durvalumab 1500 mg followed by standard of care RT/RCT

Primary Outcome Measures

Name	Time	Method
Incidence of Dose-Limiting Toxicity (DLT)	Through study development up to 5 - 6 weeks after the last session of RT/CRT for each enrolled patient	Rate of patients without Dose-Limiting Toxicity (DLT) evaluated from durvalumab administration until 5 - 6 weeks after the last session of RT/CRT.

Secondary Outcome Measures

Name	Time	Method
Safety of durvalumab followed by RT/CRT	Through study development up to 17 weeks for each enrolled patient	Presence of adverse events (AEs) assessed by (CTCAE) version 5.0
objective response rate	Through study development up to 17 weeks for each enrolled patient	percentage of patients having a complete response or a partial response as measured by RECIST 1.1.
Pathologic response rate	Through study development up to 17 weeks for each enrolled patient	Patients in whom tumor "downstaging" was achieved and making the patient eligible for surgery.
feasibility of durvalumab followed by RT/CRT	Through study development up to 3 years	proportion of enrolled patients starting RT/CRT within 4 - 5 weeks after durvalumab administration and proportion of enrolled patients completing the clinical trial.

Trial Locations

Locations (1)

Instituto Português de Oncologia do Porto FG, EPE (IPO-Porto); 🇵🇹 Porto, Portugal