Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Durvalumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immunologic Factors

1500mg every 4 weeks \[Q4W\] intravenous \[IV\], first dose within 3 days of RT initiation

Thoracic RT and Durvalumab

1500mg every 4 weeks \[Q4W\] intravenous \[IV\] up to one year

Consolidative Durvalumab

Yuanyuan Zhang, MD

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)

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

Patient registration Stage III non-small cell lung cancer Zubrod 0 or 1

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)

To determine the PFS in these patients from the time of study enrollment to documented progressive disease or death due to any cause, whichever occurs first.

To assess the safety and tolerability of concurrent durvalumab and radiotherapy compared to historical data from patients treated with standard of care chemo-radiation using adverse event according to CTCAE V.5

To determine the overall survival (OS) defined as the time from study enrollment to death due to any cause

To determine if patients will have a metastatic new lesion

To determine the local and regional control in these patients

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase II Concurrent Durvalumab and Radiotherapy for for Stage III Non-Small Cell Lung Cancer	NCT04003246	Non Small Cell ... Lung Cancer Sta...	Thoracic RT and... Consolidative D...	18 Years -	University of Texas Southwestern Medical Center
Phase II Concurrent Durvalumab and Radiotherapy for for Stage III Non-Small Cell Lung Cancer	NCT04003246	Non Small Cell ... Lung Cancer Sta...	Thoracic RT and... Consolidative D...	18 Years -	University of Texas Southwestern Medical Center

Spots Global Cancer Trial Database for thoracic rt and durvalumab