Monalizumab or Oleclumab with Durvalumab and Radiation for Lung Cancer

Recruiting in Palo Alto (17 mi)

+63 other locations

Overseen bySteven H Lin

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

This trial is for adults with stage II-III non-small cell lung cancer (NSCLC) that can't be removed by surgery. They must have a specific level of tumor protein called PD-L1, good organ function, and no liver or kidney damage. Participants need to be physically able to undergo the treatments (ECOG 0-2), have sufficient lung function, and weigh over 30 kg.

Inclusion Criteria

You had a medical check-up within the month before signing up for the study.

Your white blood cell count is at least 1500 cells per cubic millimeter.

I need extra oxygen due to my tumor but the amount has been stable.

+7 more

Participant Groups

The ARCHON-1 trial is testing if adding durvalumab to standard radiation therapy improves outcomes in NSCLC patients. It's also comparing the effects when either monalizumab or oleclumab are added into this treatment mix. The study will look at different doses of radiation and how well these combinations work together.

4Treatment groups

Experimental Treatment

Group I: Arm IV (durvalumab, oleclumab, standard RT)Experimental Treatment6 Interventions

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.

Group II: Arm III (durvalumab, monalizumab, standard RT)Experimental Treatment6 Interventions

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.

Group III: Arm II (CLOSED) (Durvalumab and standard RT)Experimental Treatment5 Interventions

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.

Group IV: Arm I (CLOSED) (Durvalumab and ACRT)Experimental Treatment5 Interventions

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.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

🇪🇺 Approved in European Union as Imfinzi for: