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

Conditions

• Locally Advanced Lung Non-Small Cell Carcinoma
• Locally Recurrent Lung Non-Small Cell Carcinoma
• Stage II Lung Cancer AJCC v8
• Stage III Lung Cancer AJCC v8
• Unresectable Lung Non-Small Cell Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Accelerated Hypofractionated Radiation Therapy — RADIATION
  160 Gy given as one 4 Gy fraction per day, 5 days per week for 15 fractions.
• Biospecimen Collection — PROCEDURE
  Undergo collection of blood samples
• Computed Tomography — PROCEDURE
  Undergo brain CT and chest CT
• Durvalumab — BIOLOGICAL
  Administered intravenously (IV) as a 1500 mg fixed dose over 60 minutes for 13 cycles (1 cycle = 4 weeks), until disease progression or toxicity or death, whichever comes first.
• Magnetic Resonance Imaging of the Brain with and without Contrast — PROCEDURE
  Undergo brain MRI
• Monalizumab — BIOLOGICAL
  Administered IV as a 1500 mg fixed dose over 60 minutes (+/- 10 minutes)
• Oleclumab — BIOLOGICAL
  Administered IV 3000 mg over 60 minutes (+/- 10 minutes)
• Radiation Therapy — RADIATION
  60 gy given as one 2 Gy fraction per day, 5 days per week for 30 fractions

Study Details

This phase I trial studies the safety of adding durvalumab to accelerated hypofractionated radiation therapy (ACRT) or conventionally fractionated radiation therapy, as well as the safety of adding either monalizumab or oleclumab to durvalumab plus conventionally fractionated radiation therapy in treating patients with non-small cell lung cancer that has spread to nearby tissue or lymph nodes (locally advanced). Accelerated hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Immunotherapy with monoclonal antibodies, such as durvalumab and monalizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Oleclumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD73, which is found on some types of tumor cells. Oleclumab may block CD73 and help the immune system kill tumor cells. It is not yet known whether adding durvalumab to ACRT or adding monalizumab or oleclumab to durvalumab plus conventionally fractionated radiation therapy will work better in treating patients with non-small cell lung cancer.

Key Dates

Start date

Oct 28, 2019

Status verified

Sep 2025

Primary completion

Oct 26, 2021

Completion

Sep 4, 2025

Study Design

Enrollment

26 participants (actual)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Arm I (CLOSED) (Durvalumab and ACRT)
  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 ACRT 1 fraction per day, 5 days per week for 15 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.
• Experimental: Arm II (CLOSED) (Durvalumab and standard RT)
  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.
• Experimental: Arm III (durvalumab, monalizumab, standard RT)
  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.
• Experimental: Arm IV (durvalumab, oleclumab, standard RT)
  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.

Primary Outcome Measure

Number of Participants Experiencing a Safety Event [ Time Frame: From start of study treatment to 90 (ACRT) or 56 (standard RT) days from the end of radiation treatment. (Approximately 104 or 70 days, respectively, from start of study treatment) ]

Locations (56)

Find similar trials in Atlanta, GA

Related Studies

• Role of Gut Microbiome and Fecal Transplant on Medication-Induced GI Complications in Patients With Cancer
  PHASE1 · Recruiting · M.D. Anderson Cancer Center · Houston, Texas
• Dyadic Yoga Intervention in Improving Physical Performance and Quality of Life in Patients With Stage I-IV Non-small Cell Lung or Esophageal Cancer Undergoing Radiotherapy and Their Caregivers
  Recruiting · M.D. Anderson Cancer Center · Houston, Texas
• Testing the Addition of a Type of Drug Called Immunotherapy to the Usual Chemotherapy Treatment for Non-small Cell Lung Cancer, an ALCHEMIST Treatment Trial (Chemo-IO [ACCIO])
  PHASE3 · Recruiting · National Cancer Institute (NCI) · Anchorage, Alaska
• Canakinumab for the Prevention of Lung Cancer, the Can-Prevent-Lung Trial
  PHASE2 · Recruiting · M.D. Anderson Cancer Center · Houston, Texas