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
Sites (56)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Emory University Hospital Midtown Coordinator of this site? Confirm its status | Atlanta | United States | Unknown status |
| Emory University Hospital/Winship Cancer Institute Coordinator of this site? Confirm its status | Atlanta | United States | Unknown status |
| Grady Health System Coordinator of this site? Confirm its status | Atlanta | United States | Unknown status |
| Emory Saint Joseph's Hospital Coordinator of this site? Confirm its status | Atlanta | United States | Unknown status |
| Augusta University Medical Center Coordinator of this site? Confirm its status | Augusta | United States | Unknown status |
| University of Maryland/Greenebaum Cancer Center Coordinator of this site? Confirm its status | Baltimore | United States | Unknown status |
| McLaren Cancer Institute-Bay City Coordinator of this site? Confirm its status | Bay City | United States | Unknown status |
| UM Upper Chesapeake Medical Center Coordinator of this site? Confirm its status | Bel Air | United States | Unknown status |
| Saint Alphonsus Cancer Care Center-Boise Coordinator of this site? Confirm its status | Boise | United States | Unknown status |
| Saint Alphonsus Cancer Care Center-Caldwell Coordinator of this site? Confirm its status | Caldwell | United States | Unknown status |
| Siteman Cancer Center at Saint Peters Hospital Coordinator of this site? Confirm its status | City of Saint Peters | United States | Unknown status |
| Michigan Healthcare Professionals Clarkston Coordinator of this site? Confirm its status | Clarkston | United States | Unknown status |
| McLaren Cancer Institute-Clarkston Coordinator of this site? Confirm its status | Clarkston | United States | Unknown status |
| Central Maryland Radiation Oncology in Howard County Coordinator of this site? Confirm its status | Columbia | United States | Unknown status |
| Ohio State University Comprehensive Cancer Center Coordinator of this site? Confirm its status | Columbus | United States | Unknown status |
| MD Anderson in The Woodlands Coordinator of this site? Confirm its status | Conroe | United States | Unknown status |
| Siteman Cancer Center at West County Hospital Coordinator of this site? Confirm its status | Creve Coeur | United States | Unknown status |
| Wayne State University/Karmanos Cancer Institute Coordinator of this site? Confirm its status | Detroit | United States | Unknown status |
| Saint Elizabeth Healthcare Edgewood Coordinator of this site? Confirm its status | Edgewood | United States | Unknown status |
| Michigan Healthcare Professionals Farmington Coordinator of this site? Confirm its status | Farmington Hills | United States | Unknown status |
| Weisberg Cancer Treatment Center Coordinator of this site? Confirm its status | Farmington Hills | United States | Unknown status |
| Singh and Arora Hematology Oncology PC Coordinator of this site? Confirm its status | Flint | United States | Unknown status |
| McLaren Cancer Institute-Flint Coordinator of this site? Confirm its status | Flint | United States | Unknown status |
| UM Baltimore Washington Medical Center/Tate Cancer Center Coordinator of this site? Confirm its status | Glen Burnie | United States | Unknown status |
| Benefis Sletten Cancer Institute Coordinator of this site? Confirm its status | Great Falls | United States | Unknown status |
| Legacy Mount Hood Medical Center Coordinator of this site? Confirm its status | Gresham | United States | Unknown status |
| M D Anderson Cancer Center Coordinator of this site? Confirm its status | Houston | United States | Unknown status |
| MD Anderson West Houston Coordinator of this site? Confirm its status | Houston | United States | Unknown status |
| Logan Health Medical Center Coordinator of this site? Confirm its status | Kalispell | United States | Unknown status |
| University of Kansas Cancer Center Coordinator of this site? Confirm its status | Kansas City | United States | Unknown status |
| University of Kansas Cancer Center - North Coordinator of this site? Confirm its status | Kansas City | United States | Unknown status |
| University of Kansas Cancer Center-West Coordinator of this site? Confirm its status | Kansas City | United States | Unknown status |
| Mid-Michigan Physicians-Lansing Coordinator of this site? Confirm its status | Lansing | United States | Unknown status |
| Karmanos Cancer Institute at McLaren Greater Lansing Coordinator of this site? Confirm its status | Lansing | United States | Unknown status |
| McLaren Cancer Institute-Lapeer Region Coordinator of this site? Confirm its status | Lapeer | United States | Unknown status |
| MD Anderson League City Coordinator of this site? Confirm its status | League City | United States | Unknown status |
| University of Kansas Cancer Center - Lee's Summit Coordinator of this site? Confirm its status | Lee's Summit | United States | Unknown status |
| West Virginia University Healthcare Coordinator of this site? Confirm its status | Morgantown | United States | Unknown status |
| McLaren Cancer Institute-Macomb Coordinator of this site? Confirm its status | Mount Clemens | United States | Unknown status |
| Saint Alphonsus Cancer Care Center-Nampa Coordinator of this site? Confirm its status | Nampa | United States | Unknown status |
| University of Kansas Cancer Center at North Kansas City Hospital Coordinator of this site? Confirm its status | North Kansas City | United States | Unknown status |
| University of Oklahoma Health Sciences Center Coordinator of this site? Confirm its status | Oklahoma City | United States | Unknown status |
| Nebraska Methodist Hospital Coordinator of this site? Confirm its status | Omaha | United States | Unknown status |
| University of Kansas Cancer Center-Overland Park Coordinator of this site? Confirm its status | Overland Park | United States | Unknown status |
| McLaren Cancer Institute-Northern Michigan Coordinator of this site? Confirm its status | Petoskey | United States | Unknown status |
| Thomas Jefferson University Hospital Coordinator of this site? Confirm its status | Philadelphia | United States | Unknown status |
| McLaren-Port Huron Coordinator of this site? Confirm its status | Port Huron | United States | Unknown status |
| Legacy Good Samaritan Hospital and Medical Center Coordinator of this site? Confirm its status | Portland | United States | Unknown status |
| Siteman Cancer Center-South County Coordinator of this site? Confirm its status | St Louis | United States | Unknown status |
| Washington University School of Medicine Coordinator of this site? Confirm its status | St Louis | United States | Unknown status |
| Siteman Cancer Center at Christian Hospital Coordinator of this site? Confirm its status | St Louis | United States | Unknown status |
| MD Anderson in Sugar Land Coordinator of this site? Confirm its status | Sugar Land | United States | Unknown status |
| Michigan Healthcare Professionals Troy Coordinator of this site? Confirm its status | Troy | United States | Unknown status |
| Legacy Salmon Creek Hospital Coordinator of this site? Confirm its status | Vancouver | United States | Unknown status |
| University of Kansas Hospital-Westwood Cancer Center Coordinator of this site? Confirm its status | Westwood | United States | Unknown status |
| Lankenau Medical Center Coordinator of this site? Confirm its status | Wynnewood | United States | Unknown status |
This page is information, not medical advice. Discuss any trial with your doctor.