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

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.

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

Interventions

RADIATION

Accelerated Hypofractionated Radiation Therapy

160 Gy given as one 4 Gy fraction per day, 5 days per week for 15 fractions.

PROCEDURE

Biospecimen Collection

Undergo collection of blood samples

PROCEDURE

Computed Tomography

Undergo brain CT and chest CT

BIOLOGICAL

Durvalumab

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.

PROCEDURE

Magnetic Resonance Imaging of the Brain with and without Contrast

Undergo brain MRI

BIOLOGICAL

Monalizumab

Administered IV as a 1500 mg fixed dose over 60 minutes (+/- 10 minutes)

BIOLOGICAL

Oleclumab

Administered IV 3000 mg over 60 minutes (+/- 10 minutes)

RADIATION

Radiation Therapy

60 gy given as one 2 Gy fraction per day, 5 days per week for 30 fractions

Sponsors & Collaborators

• NRG Oncology

  collaborator OTHER

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Steven H Lin · NRG Oncology

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-10-28

Primary Completion

2021-10-26

Completion

2025-09-04

FDA Drug

Yes

Countries

• United States

Study Locations