Testing the Safety of Adding Either Monalizumab (IPH2201) or Oleclumab (MEDI9447) to Durvalumab (MEDI4736) plus Standard Radiation Therapy for Locally Advanced Non-small Cell Lung Cancer (NSCLC), ARCHON-1 Trial

Summary

Objectives

PRIMARY OBJECTIVES:
I. To evaluate if the addition of durvalumab to two schedules of radiation therapies (60 Gy in 30 fractions or 60 Gy in 15 fractions) is safe.
II. To evaluate if the addition of either monalizumab or oleclumab to radiation therapy (RT) (60 Gy in 30 fractions) + durvalumab is safe.

SECONDARY OBJECTIVES:
I. To examine if the addition of durvalumab to radiation therapy as well as the addition of either monalizumab or oleclumab is feasible.
II. To assess toxicities associated with the addition of durvalumab to radiation therapy as well as the addition of either monalizumab or oleclumab.
III. To obtain preliminary estimates of progression-free survival (PFS), using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, in patients who received durvalumab added to radiation, and either monalizumab or oleclumab added to RT (60 Gy in 30 fractions) + durvalumab.

EXPLORATORY OBJECTIVES:
I. To assess the impact the addition of durvalumab to RT and either monalizumab or oleclumab to RT (60 Gy in 30 fractions) + durvalumab have on progression-free survival, using Immune-Related Response Criteria (irRC) guidelines.
II. To assess the changes in circulating tumor cells (CTCs) and various immune parameters during treatment with durvalumab and radiotherapy and changes after completion of treatment.

OUTLINE: Patients are randomized to Arm I or Arm II (CLOSED TO ACCRUAL).

ARM I (CLOSED): Starting 2 weeks prior to radiation therapy, patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo accelerated hypofractionated radiation therapy (ACRT) 1 fraction per day, 5 days per week for 15 fractions. Patients also undergo brain magnetic resonance imaging (MRI) or computed tomography (CT) scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.

ARM II (CLOSED): Starting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.

Patients are assigned to Arm III or Arm IV.

ARM III: Starting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes and monalizumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.

ARM IV: Starting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Patients also receive oleclumab IV over 60 minutes on days 1 and 15 of cycles 1-2, then on day 1 of cycles thereafter. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 4 months for 1 year.