NCT04003246

Phase II Concurrent Durvalumab and Radiotherapy for for Stage III Non-Small Cell Lung Cancer

Phase II Concurrent Durvalumab (MEDI4736) and Radiotherapy Followed by Consolidative Durvalumab (MEDI4736) for Stage III Non-Small Cell Lung Cancer (NSCLC)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: University of Texas Southwestern Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Single arm, Phase II trial of concurrent Durvalumab (MEDI 4736) and radiotherapy followed by consolidative Durvalumb (MEDI 4736) for Stage III Non-Small Cell Lung Cancer (NSCLC)

Detailed description

Immunotherapy has significantly improved the survival outcomes of patients with various cancer types including thoracic malignancies. In the PACIFIC study, patients with locally advanced NSCLC were randomized to the anti-PDL1 antibody durvalumab or placebo for up to 12 months after completion of concurrent chemoradiation. While NSCLC is typically considered relatively non-immunogenic, RT is thought to augment tumor immunogenicity(Iyengar \& Gerber, 2013). The abscopal effect refers to the observation that the benefit seen in PACIFIC, along with the growing role of immunotherapy for the treatment advanced (stage IV) NSCLC, suggests that earlier exposure to durvalumab may improve outcomes and be well tolerated, thereby permitting de-escalation of therapy through removal of conventional chemotherapy from these regimens to a local area results in an antitumor effect distant to the radiation site. Durvalumab (Imfimzi; MEDI4736; AstraZeneca) is a human monoclonal antibody of the immunoglobulin (Ig) G1 kappa subclass that inhibits binding of PD-L1 (B7-H1, CD274) to PD-1 (CD279) and CD80 (B7-1). MEDI4736 is composed of 2 identical heavy chains and 2 identical light chains, with an overall molecular weight of approximately 149 kDa. MEDI4736 contains a triple mutation in the constant domain of the Ig G1 heavy chain that reduces binding to complement protein C1q and the Fcγ receptors involved in triggering effector function. Durvlumab binds with high affinity and specificity to human PD-L1 and blocks its interaction with PD-1 and CD80

Conditions

• Non Small Cell Lung Cancer
• Lung Cancer Stage III

Interventions

Type	Name	Description
RADIATION	Thoracic RT and Durvalumab	1500mg every 4 weeks \[Q4W\] intravenous \[IV\], first dose within 3 days of RT initiation
DRUG	Consolidative Durvalumab	1500mg every 4 weeks \[Q4W\] intravenous \[IV\] up to one year

Timeline

• Start date: 2020-04-03
• Primary completion: 2022-06-15
• Completion: 2024-11-05
• First posted: 2019-07-01
• Last updated: 2025-03-21
• Results posted: 2025-03-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study