NCT03801902

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

Completed Phase 1 Results posted Last updated 23 September 2025

What this trial tests

Phase 1 trial testing Accelerated Hypofractionated Radiation Therapy in Locally Advanced Lung Non-Small Cell Carcinoma in 26 participants. Completed in 4 September 2025.

Timeline

28 October 2019

Primary endpoint
26 October 2021

4 September 2025

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	26
Start date	28 October 2019
Primary completion	26 October 2021
Estimated completion	4 September 2025
Sites	56 locations across United States

Drugs / interventions tested

• Accelerated Hypofractionated Radiation Therapy
• Biospecimen Collection — full drug profile →
• Computed Tomography
• Durvalumab — full drug profile →
• Magnetic Resonance Imaging of the Brain with and without Contrast
• Monalizumab — full drug profile →
• Oleclumab
• Radiation Therapy — full drug profile →

Conditions studied

• Locally Advanced Lung Non-Small Cell Carcinoma — all drugs for Locally Advanced Lung Non-Small Cell Carcinoma →
• Locally Recurrent Lung Non-Small Cell Carcinoma — all drugs for Locally Recurrent Lung Non-Small Cell Carcinoma →
• Stage II Lung Cancer AJCC v8 — all drugs for Stage II Lung Cancer AJCC v8 →
• Stage III Lung Cancer AJCC v8 — all drugs for Stage III Lung Cancer AJCC v8 →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Locally Advanced Lung Non-Small Cell Carcinoma or Locally Recurrent Lung Non-Small Cell Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Experiencing a Safety Event Primary · From start of study treatment to 90 (ACRT) or 56 (standard RT) days from the end of radiation treatment. (Approximately 104 or 70 days, respectively, from start of study treatment)

Safety event is defined as one of the following: * Grade 4-5 non-hematologic protocol-defined serious adverse event (SAE) possibly, probably, or definitely related to protocol treatment occurring within 90 days from radiation therapy (RT) start for Arm 1 or within 8 weeks from RT start for Arm 2; * Any adverse event possibly, probably, or definitely related to protocol treatment that leads to missing at least 2 doses of durvalumab within 90 days from RT start for Arm 1 or within 8 weeks from RT start for Arm 2; * Permanent discontinuation of durvalumab due to an adverse event possibly, probab

Group	Value	95% CI
Arm I (CLOSED) (Durvalumab and ACRT)	0
Arm II (CLOSED) (Durvalumab and Standard RT)	1

Percentage of Participants Who Received at Least 80% of Planned Durvalumab Dose During First 8 Weeks Following Initial Dose Secondary · From start of durvalumab to 8 weeks

Group	Value	95% CI
Arm I (CLOSED) (Durvalumab and ACRT)	84.6	54.6 – 98.1
Arm II (CLOSED) (Durvalumab and Standard RT)	75.0	42.8 – 94.5

Distribution of Participants by Highest Grade Adverse Event Secondary · From registration to last follow-up at time of initial analysis. Maximum follow-up was 23.2 months

Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grades adverse event severity from 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

Group	Value	95% CI
Arm I (CLOSED) (Durvalumab and ACRT)	2
Arm II (CLOSED) (Durvalumab and Standard RT)	0
Arm I (CLOSED) (Durvalumab and ACRT)	5
Arm II (CLOSED) (Durvalumab and Standard RT)	3
Arm I (CLOSED) (Durvalumab and ACRT)	4
Arm II (CLOSED) (Durvalumab and Standard RT)	8
Arm I (CLOSED) (Durvalumab and ACRT)	1
Arm II (CLOSED) (Durvalumab and Standard RT)	0

Percentage of Participants Experiencing a Grade 4 or Higher Non-hematologic Adverse Event Secondary · From registration to last follow-up at time of initial analysis. Maximum follow-up was 23.2 months.

Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grades adverse event severity from 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.

Group	Value	95% CI
Arm I (CLOSED) (Durvalumab and ACRT)	7.7	0.2 – 36.0
Arm II (CLOSED) (Durvalumab and Standard RT)	8.3	0.2 – 38.5

Progression-free Survival Secondary · From registration to two years after protocol treatment, which lasted up to 12 months. Maximum follow-up was 38.3 months.

Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as an increase \>= 20% of the sum of longest diameters of target lesions compared with nadir (minimum 5 mm) or progression of non-target lesions or new lesion. Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. Analysis was planned to occur two years after end of protocol treatment, which could last up to 12 months. No formal testing was p

Group	Value	95% CI
Arm I (CLOSED) (Durvalumab and ACRT)	20.4	7.9 – NA
Arm II (CLOSED) (Durvalumab and Standard RT)	30.2	8.2 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: From registration to two years after protocol treatment, which lasted up to 12 months. This time frame corresponds to the last outcome measure analyzed, progression-free survival.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm I (CLOSED) (Durvalumab and ACRT)

Serious: 6/13 (46%)

Deaths: 4/13

Arm II (CLOSED) (Durvalumab and Standard RT)

Serious: 5/12 (42%)

Deaths: 2/12

Serious adverse events (15 terms)

Reaction	System	Arm I (CLOSED) (Durvalumab…	Arm II (CLOSED) (Durvaluma…
Atrial fibrillation	Cardiac disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Atrial flutter	Cardiac disorders	—	—
Infections and infestations - Other	Infections and infestations	—	—
Lung infection	Infections and infestations	—	—
Alanine aminotransferase increased	Investigations	—	—
Cardiac troponin T increased	Investigations	—	—
Ejection fraction decreased	Investigations	—	—
Renal calculi	Renal and urinary disorders	—	—
Bronchopulmonary hemorrhage	Respiratory, thoracic and mediastinal disorders	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Pneumothorax	Respiratory, thoracic and mediastinal disorders	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Hypertension	Vascular disorders	—	—

Other adverse events (120 terms — click to expand)

Reaction	System	Arm I (CLOSED) (Durvalumab…	Arm II (CLOSED) (Durvaluma…
Fatigue	General disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—
Lymphocyte count decreased	Investigations	—	—
Anemia	Blood and lymphatic system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Esophagitis	Gastrointestinal disorders	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Dysphagia	Gastrointestinal disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Sore throat	Respiratory, thoracic and mediastinal disorders	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Non-cardiac chest pain	General disorders	—	—
Dermatitis radiation	Injury, poisoning and procedural complications	—	—
Alkaline phosphatase increased	Investigations	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—
Wheezing	Respiratory, thoracic and mediastinal disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Palpitations	Cardiac disorders	—	—
Tinnitus	Ear and labyrinth disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—
Gastroesophageal reflux disease	Gastrointestinal disorders	—	—
Edema limbs	General disorders	—	—
General disorders and administration site conditions - Other	General disorders	—	—
Shingles	Infections and infestations	—	—
Sinusitis	Infections and infestations	—	—
Blood lactate dehydrogenase increased	Investigations	—	—
Creatinine increased	Investigations	—	—
Platelet count decreased	Investigations	—	—
Weight loss	Investigations	—	—
Hypocalcemia	Metabolism and nutrition disorders	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Arthritis	Musculoskeletal and connective tissue disorders	—	—

Most-reported serious reactions: Atrial fibrillation, Dyspnea, Atrial flutter, Infections and infestations - Other, Lung infection, Alanine aminotransferase increased, Cardiac troponin T increased, Ejection fraction decreased.

Data from ClinicalTrials.gov NCT03801902 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Radiotherapy combined with immunotherapy: the dawn of cancer treatment.
   Zhang Z, Liu X, Chen D, Yu J. · · 2022 · cited 463× · PMID 35906199 · DOI 10.1038/s41392-022-01102-y
2. Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial.
   Jabbour SK, Lee KH, Frost N, Breder V, et al · · 2021 · cited 185× · PMID 34086039 · DOI 10.1001/jamaoncol.2021.2301
3. The cutting-edge progress of immune-checkpoint blockade in lung cancer.
   Zhou F, Qiao M, Zhou C. · · 2021 · cited 177× · PMID 33177696 · DOI 10.1038/s41423-020-00577-5
4. Radiation-induced lung toxicity - cellular and molecular mechanisms of pathogenesis, management, and literature review.
   Käsmann L, Dietrich A, Staab-Weijnitz CA, Manapov F, et al · · 2020 · cited 171× · PMID 32912295 · DOI 10.1186/s13014-020-01654-9
5. Management of locally advanced non-small cell lung cancer: State of the art and future directions.
   Miao D, Zhao J, Han Y, Zhou J, et al · · 2024 · cited 99× · PMID 37985191 · DOI 10.1002/cac2.12505
6. Combined treatment of non-small cell lung cancer using radiotherapy and immunotherapy: challenges and updates.
   Shang S, Liu J, Verma V, Wu M, et al · · 2021 · cited 68× · PMID 34658186 · DOI 10.1002/cac2.12226
7. Radioresistance of Non-Small Cell Lung Cancers and Therapeutic Perspectives.
   Césaire M, Montanari J, Curcio H, Lerouge D, et al · · 2022 · cited 35× · PMID 35740495 · DOI 10.3390/cancers14122829
8. Is the Combination of Immunotherapy and Radiotherapy in Non-small Cell Lung Cancer a Feasible and Effective Approach?
   Spaas M, Lievens Y. · · 2019 · cited 31× · PMID 31788476 · DOI 10.3389/fmed.2019.00244