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

Tremelimumab

Antineoplastic Agents, Immunological

Drug: Durvalumab Other Names: MEDI4736

MEDI4736 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles Intervention: Radiation: Thoracic Radiation 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction

Intervention: Procedure/Surgery: lobectomy patients may proceed to surgery post drug and radiation intervention for lung lobectomy

Intervention: Drug: Standard of care adjuvant chemotherapy patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Drugs: Durvalumab + Tremelimumab Other Names: MEDI4736 and CP-675 MEDI4736 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles + CP-675 206 75mg via IV infusion every 4 weeks up 3 doses/cycles Intervention: Radiation: Thoracic Radiation 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction Intervention: Procedure/Surgery: lobectomy patients may proceed to surgery post drug and radiation intervention for lung lobectomy

Intervention: Drug: Standard of care adjuvant chemotherapy patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

1500mg via IV infusion every 4 weeks for up to 3 doses/cycles

5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction

Thoracic Radiation

patients may proceed to surgery post drug and radiation intervention for lung lobectomy

lobectomy

patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Standard of care adjuvant chemotherapy

Patrick Forde, MD

This is a pilot study of neoadjuvant 'immunoradiation' (durvalumab or durvalumab plus tremelimumab) administered every 4 weeks for 2 doses, concurrently with standard thoracic radiation (RT) (45Gy in 25 fractions), with one dose of immunotherapy alone delivered in the pre-surgical window, prior to surgical resection, for patients with stage IIIA NSCLC that is deemed resectable with a lobectomy by a thoracic surgeon. If preliminary safety of the durvalumab/thoracic RT combination is established, a second cohort investigating the combination of durvalumab/tremelimumab/thoracic RT prior to surgical resection will be opened. After surgical resection, patients may receive standard adjuvant chemotherapy, as deemed appropriate by the treating investigator.

Neoadjuvant Immunoradiation for Resectable Non-Small Cell Lung Cancer

Neoadjuvant Immunoradiation for Stage III Resectable Non-Small Cell Lung Cancer

Number of participants experiencing adverse events as defined by CTCAE v4.0.

Number of participants with stage III resectable NSCLC who received durvalumab or durvalumab plus tremelimumab concurrently with thoracic radiation (RT) in the pre-surgical window prior to surgical resection, for whom planned surgical resection was not delayed.

Number of participants who experience post-operative death. Calculated through log-rank test and Cox proportional hazards (PH) model. The values in the table represent the number of participants who experienced post-operative death.

Percentage of participants with major pathologic response (MPR), partial response (PR) or no response (NR), where MPR is \>90% reduction in tumor cells, PR = 10-90% or NR = 0-10%. The percentage of patients whose tumor samples achieve MPR, PR and NR will be tabulated.

Percentage of participants with complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD) as defined by RECIST 1.1 and immune-related RECIST criteria when treated with preoperative immunoradiation followed by surgery. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, PD is \>20% increase in sum of diameters of target lesions, SD is \<30% decrease or \<20% increase in sum of diameters of target lesions.

Time from first evidence of response until recurrence when treated with preoperative immunoradiation followed by surgery. Calculated through log-rank test and Cox proportional hazards (PH) model.

Number of months alive after treatment with preoperative immunoradiation followed by surgery. Calculated through log-rank test and Cox proportional hazards (PH) model.

AstraZeneca

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

The number of participants at risk for SAEs, AEs, and all-cause mortality is zero for the Durvalumab and Trememlimumab With Radiation arm because there were no patients enrolled onto arm 2, and no data was collected.

Drug: Durvalumab Other Names: MEDI4736

MEDI4736 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles Intervention: Radiation: Thoracic Radiation 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction

Intervention: Procedure/Surgery: lobectomy patients may proceed to surgery post drug and radiation intervention for lung lobectomy

Intervention: Drug: Standard of care adjuvant chemotherapy patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Durvalumab: 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles

Thoracic Radiation: 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction

lobectomy: patients may proceed to surgery post drug and radiation intervention for lung lobectomy

Standard of care adjuvant chemotherapy: patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Durvalumab With Radiation

Drugs: Durvalumab + Tremelimumab Other Names: MEDI4736 and CP-675 MEDI4736 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles + CP-675 206 75mg via IV infusion every 4 weeks up 3 doses/cycles Intervention: Radiation: Thoracic Radiation 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction Intervention: Procedure/Surgery: lobectomy patients may proceed to surgery post drug and radiation intervention for lung lobectomy

Intervention: Drug: Standard of care adjuvant chemotherapy patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Durvalumab: 1500mg via IV infusion every 4 weeks for up to 3 doses/cycles

Tremelimumab: 75mg via IV infusion every 4 weeks

Thoracic Radiation: 5 days per week in once daily fractionation, 1.8-2.0 Gy per fraction

lobectomy: patients may proceed to surgery post drug and radiation intervention for lung lobectomy

Standard of care adjuvant chemotherapy: patients may or may not proceed to adjuvant chemotherapy post trial drug and radiation intervention and surgery

Durvalumab and Trememlimumab With Radiation

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race/Ethnicity

Race/Ethnicity, Customized

Canada

United States

Region of Enrollment

The protocol planned for a second cohort for patients to be treated with durvalumab and trememlimumab with radiation, however, due to low accrual in cohort 1, there was no second cohort.

Jasmine Brooks, Senior Research Program Coordinator

all participants who were assigned to the durvalumab with radiation arm

Toxicities as Measured by Number of Participants Experiencing Adverse Events

The study closed early due to low accrual on Arm A Durvalumab with Radiation so no data was collected for Arm B Durvalumab and Trememlimumab with Radiation.

Feasibility of Preoperative Immunoradiation

The study closed to enrollment before patients could be enrolled onto Arm B: durvalumab and trememlimumab with radiation

Spots Global Cancer Trial Database for standard of care adjuvant chemotherapy