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NCT03801902CompletedPhase 1

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

Phase I Trial of Radiotherapy Combined With Durvalumab Alone Plus Either Monalizumab or Oleclumab in PD-L1 High Locally Advanced Non-Small Cell Lung Cancer (NSCLC) (ARCHON-1)

Source: ClinicalTrials.gov · Last updated 23 Sept 2025

Brief summary (registry, in English)

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.

Status (registry)
Completed
Phase (registry)
Phase 1
Study type
Interventional
Enrollment
26 (actual)
First submitted
11 Jan 2019
Start date
28 Oct 2019
Primary completion date
26 Oct 2021
Lead sponsor
National Cancer Institute (NCI)
Diseases
Lung cancer
NCT number
NCT03801902

What you commit to

  • Study type: Interventional · Phase 1
  • Participants enrolled: 26
  • From 28 Oct 2019 to the primary completion date, 26 Oct 2021
  • 56 sites in 1 country
  • Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Prior treatment

  • Prior chemotherapy or systemic therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields so that cumulative composite dose combining previous plan and current plan to be within 80 Gy to the trachea, major blood vessels, esophagus, and heart, and 55 Gy to the spinal cord (if such patients are being considered, this will need to be centrally reviewed). Prior chest radiation without overlap is permissible
  • Prior history of myocardial infarction, stroke, or transient ischemic attack in the past 3 months
  • Major surgical procedure (as defined by the investigator) within 28 days prior to registration
    • Note:
    • Local surgery of isolated lesions for palliative intent is acceptable
    • Other major surgery before first dose of immunotherapy is not acceptable
  • Current or prior use of immunosuppressive medication within 14 days before registration. (Note: immunosuppressive medication within 14 days before immunotherapy is not acceptable). The following are exceptions to this criterion:
    • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection);
    • Systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent;
    • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Receipt of live attenuated vaccine within 30 days prior to registration

Other illness

  • Definitive clinical or radiologic evidence of metastatic disease
  • Prior invasive malignancy (except those with a negligible risk of metastasis or death and with expected curative outcome \[such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent\] or undergoing active surveillance per standard-of-care management \[e.g., chronic lymphocytic leukemia (CLL) Rai stage 0, prostate cancer with Gleason score =\< 6, and prostate specific antigen (PSA) =\< 10 mg/mL\]) unless disease free for a minimum of 3 years
  • History of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Patients with a history of treated autoimmune thyroid disease requiring thyroid replacement but not immunosuppressives, as well as type 1 diabetes, are permitted. Patients with vitiligo, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on chest PET/CT or CT scan
  • History of allogenic organ transplantation
  • History of leptomeningeal carcinomatosis
  • History of active primary immunodeficiency
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

Lab values

  • Severe, active co-morbidity defined as follows:
    • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease;
    • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications;
    • Active tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis \[TB\] testing in line with local practice);
    • Active hepatitis B (chronic or acute) or hepatitis C infection. Patients with past or resolved hepatitis B infection defined as having a negative hepatitis B surface antigen (HBsAg) test, a positive anti-HBc (antibody to hepatitis B core antigen), and a negative viral deoxyribonucleic acid (DNA) test (only obtained if HBsAg is found positive) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
  • Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade \>= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:
    • Patients with grade \>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician.
    • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study physician

Other

  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during treatment and for 3 months after the last dose of treatment; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
  • Women who are breastfeeding and unwilling to discontinue

Who the study is looking for

  • Pathologic (cytological or histological) proof of diagnosis of stage II-III (American Joint Committee on Cancer \[AJCC\] 8th edition \[ed.\]) unresectable or inoperable, non-metastatic non-small cell lung cancer (NSCLC) within 60 days prior to registration, with no liver or renal end organ damage, as determined by normal laboratory values noted below. Locally recurrent, N1-N3 disease following surgery without prior radiation therapy is eligible. Patients with N1 to N3 and undetectable primary lung tumors (T0) are eligible
  • Pathological diagnosis of PD-L1 high expressing tumors (\>= 50%) within 60 days prior to registration (using Dako 22C3 immunohistochemistry \[IHC\] antibody or the Ventana SP263 antibody platforms) performed at a Clinical Laboratory Improvement Act (CLIA)-certified lab
  • Appropriate stage for study entry based on the following diagnostic workup:
    • History/physical examination within 30 days prior to registration;
    • Positron emission tomography (PET)/computed tomography (CT) scan for staging within 30 days prior to registration (note: if CT portion of PET/CT scan is not of diagnostic quality, then a separate CT scan with contrast is required);
    • Magnetic resonance imaging (MRI) scan of the brain with contrast; if medically contraindicated, then CT scan of the brain with contrast (unless medically contraindicated) is acceptable, within 30 days prior to registration;
    • Sufficient lung function with forced expiratory volume in 1 second (FEV1) \>= 0.8 liter or \>= 35% predicted and carbon monoxide diffusing capability (DLCO) \>= 40% with or without bronchodilator within 30 days prior to registration;
    • Patients who meet the criterion above without oxygen (O2), but who need acute (started within 10 days prior to registration) supplemental oxygen due to tumor-caused obstruction/hypoxia are eligible, provided the amount of the O2 needed has been stable
  • Age ≥ 18
  • Minimum body weight \>= 40 kg
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 30 days prior to registration
  • Absolute neutrophil count (ANC) \>= 1500 cells/mm\^3 (within 30 days prior to registration)
  • Lymphocyte count \>= 500 cells/mm\^3 (within 30 days prior to registration)
  • Platelet count \>= 100,000 cells/mm\^3 (within 30 days prior to registration)
  • Hemoglobin \>= 9.0 g/dL (within 30 days prior to registration) (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 9.0 g/dl is acceptable)
  • Creatinine clearance \>= 40 mL/min by the Cockcroft-Gault (C-G) equation
  • Total bilirubin =\< 1.5 x upper limit of normal (ULN) with the following exception (within 30 days prior to registration):
    • Patients with known Gilbert disease who have serum bilirubin level =\< 3 x ULN may be enrolled
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN (within 30 days prior to registration)
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients, obtained within 14 days prior to registration. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
    • Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
    • Women \>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
  • Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements:
    • They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective
    • They must have a CD4 count of greater than 250 cells/mcL
    • They must not be receiving prophylactic therapy for an opportunistic infection
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (56)

Sites in registry order. Pick your city on the disease page to sort them by distance.

SiteCityCountrySite status
Emory University Hospital Midtown
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AtlantaUnited StatesUnknown status
Emory University Hospital/Winship Cancer Institute
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AtlantaUnited StatesUnknown status
Grady Health System
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AtlantaUnited StatesUnknown status
Emory Saint Joseph's Hospital
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AtlantaUnited StatesUnknown status
Augusta University Medical Center
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AugustaUnited StatesUnknown status
University of Maryland/Greenebaum Cancer Center
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BaltimoreUnited StatesUnknown status
McLaren Cancer Institute-Bay City
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Bay CityUnited StatesUnknown status
UM Upper Chesapeake Medical Center
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Bel AirUnited StatesUnknown status
Saint Alphonsus Cancer Care Center-Boise
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BoiseUnited StatesUnknown status
Saint Alphonsus Cancer Care Center-Caldwell
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CaldwellUnited StatesUnknown status
Siteman Cancer Center at Saint Peters Hospital
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City of Saint PetersUnited StatesUnknown status
Michigan Healthcare Professionals Clarkston
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ClarkstonUnited StatesUnknown status
McLaren Cancer Institute-Clarkston
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ClarkstonUnited StatesUnknown status
Central Maryland Radiation Oncology in Howard County
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ColumbiaUnited StatesUnknown status
Ohio State University Comprehensive Cancer Center
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ColumbusUnited StatesUnknown status
MD Anderson in The Woodlands
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ConroeUnited StatesUnknown status
Siteman Cancer Center at West County Hospital
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Creve CoeurUnited StatesUnknown status
Wayne State University/Karmanos Cancer Institute
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DetroitUnited StatesUnknown status
Saint Elizabeth Healthcare Edgewood
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EdgewoodUnited StatesUnknown status
Michigan Healthcare Professionals Farmington
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Farmington HillsUnited StatesUnknown status
Weisberg Cancer Treatment Center
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Farmington HillsUnited StatesUnknown status
Singh and Arora Hematology Oncology PC
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FlintUnited StatesUnknown status
McLaren Cancer Institute-Flint
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FlintUnited StatesUnknown status
UM Baltimore Washington Medical Center/Tate Cancer Center
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Glen BurnieUnited StatesUnknown status
Benefis Sletten Cancer Institute
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Great FallsUnited StatesUnknown status
Legacy Mount Hood Medical Center
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GreshamUnited StatesUnknown status
M D Anderson Cancer Center
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HoustonUnited StatesUnknown status
MD Anderson West Houston
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HoustonUnited StatesUnknown status
Logan Health Medical Center
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KalispellUnited StatesUnknown status
University of Kansas Cancer Center
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Kansas CityUnited StatesUnknown status
University of Kansas Cancer Center - North
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Kansas CityUnited StatesUnknown status
University of Kansas Cancer Center-West
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Kansas CityUnited StatesUnknown status
Mid-Michigan Physicians-Lansing
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LansingUnited StatesUnknown status
Karmanos Cancer Institute at McLaren Greater Lansing
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LansingUnited StatesUnknown status
McLaren Cancer Institute-Lapeer Region
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LapeerUnited StatesUnknown status
MD Anderson League City
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League CityUnited StatesUnknown status
University of Kansas Cancer Center - Lee's Summit
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Lee's SummitUnited StatesUnknown status
West Virginia University Healthcare
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MorgantownUnited StatesUnknown status
McLaren Cancer Institute-Macomb
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Mount ClemensUnited StatesUnknown status
Saint Alphonsus Cancer Care Center-Nampa
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NampaUnited StatesUnknown status
University of Kansas Cancer Center at North Kansas City Hospital
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North Kansas CityUnited StatesUnknown status
University of Oklahoma Health Sciences Center
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Oklahoma CityUnited StatesUnknown status
Nebraska Methodist Hospital
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OmahaUnited StatesUnknown status
University of Kansas Cancer Center-Overland Park
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Overland ParkUnited StatesUnknown status
McLaren Cancer Institute-Northern Michigan
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PetoskeyUnited StatesUnknown status
Thomas Jefferson University Hospital
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PhiladelphiaUnited StatesUnknown status
McLaren-Port Huron
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Port HuronUnited StatesUnknown status
Legacy Good Samaritan Hospital and Medical Center
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PortlandUnited StatesUnknown status
Siteman Cancer Center-South County
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St LouisUnited StatesUnknown status
Washington University School of Medicine
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St LouisUnited StatesUnknown status
Siteman Cancer Center at Christian Hospital
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St LouisUnited StatesUnknown status
MD Anderson in Sugar Land
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Sugar LandUnited StatesUnknown status
Michigan Healthcare Professionals Troy
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TroyUnited StatesUnknown status
Legacy Salmon Creek Hospital
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VancouverUnited StatesUnknown status
University of Kansas Hospital-Westwood Cancer Center
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WestwoodUnited StatesUnknown status
Lankenau Medical Center
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WynnewoodUnited StatesUnknown status

This page is information, not medical advice. Discuss any trial with your doctor.