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Phase 1 Completed N=26 Randomized Treatment

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

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
Source: ClinicalTrials.gov NCT03801902 ↗
Enrolled (actual)
26
Serious AEs
44.0%
Results posted
Jun 2025
Primary outcomePrimary: Number of Participants Experiencing a Safety Event — 0; 1 Participants

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Participants Experiencing a Safety Event
0; 1
SECONDARY
Percentage of Participants Who Received at Least 80% of Planned Durvalumab Dose During First 8 Weeks Following Initial Dose
84.6; 75.0
SECONDARY
Percentage of Participants Who Received at Least 80% of Planned Dose of Monalizumab or Oleclumab During the First 8 Weeks Following the Initial Dose (Feasibility)
SECONDARY
Distribution of Participants by Highest Grade Adverse Event
2; 0; 5; 3; 4; 8
SECONDARY
Percentage of Participants Experiencing a Grade 4 or Higher Non-hematologic Adverse Event
7.7; 8.3
SECONDARY
Progression-free Survival
20.4; 30.2

Eligibility Criteria

Inclusion Criteria

  • 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 = = 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

Exclusion Criteria

  • 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03801902). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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