RADICAL-IO: thRee Cycles of immunotherApy Without raDical Therapy In mediCALly InOperable Stage I Non-small Cell Lung Cancer

NCT07808138 | Not Yet Recruiting Phase 2 FDA Drug

• 3 other identifiers: M25RIO2025-524305-32-002025
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

Traditionally, chemotherapy and/or immunotherapy are combined with surgery or radiotherapy to cure patients with lung cancer. However, some patients treated with immunotherapy appear to be cured before surgery or radiotherapy. In this study, we will select patients with a high chance to respond to immunotherapy. These patients will be treated with immunotherapy alone, thereby evaluating whether these patients can be cured without surgery or radiotherapy.

Conditions

Non Small Cell Lung Cancer; Immunotherapy

Keywords

early stage non small cell lung cancer; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Recurrence free survival (RFS) as per RECIST 1.1

  Time from first cemiplimab administration to disease recurrence/progression as per RECIST 1.1, fatal TRAEs or NSCLC-related death.

  24 months

Secondary Outcomes (7)

• Estimate event free survival

  24 months

• Evaluate safety

  24 months

• Estimate survival

  24 months

• Estimate location of disease recurrence

  24 months

• Objective reponse rate (ORR)

  24 months

Study Arms (1)

Three cycles of cemiplimab

ACTIVE COMPARATOR

Three cycles of cemiplimab

Drug: Cemiplimab 350 mg IV

Interventions

Cemiplimab 350 mg IV DRUG

three cycles of 350 milligrams of cemiplimab intravenously every three weeks

Also known as: Libtayo

Three cycles of cemiplimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have pathologically proven newly diagnosed, treatment-naive stage IA (i.e. tumor diameter ≤ 3 cm) NSCLC according to the 9th AJCC/UICC staging classification (30).
• Be willing and able to provide written informed consent/assent for the trial.
• Be 18 years of age on day of signing informed consent.
• Should have measurable disease according to RECIST 1.1.
• Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.
• Molecular analysis using next-generation sequencing (NGS) should be performed to identify oncogenic driver alterations and/or STK11 or KEAP1 mutations. If NGS is not available, the patient must have a smoking history of at least 10 packyears.
• PD-L1 TPS should be at least 50%.
• Should have an indication for SABR determined by the multidisciplinary team meeting.
• Demonstrate adequate organ function as defined in Table 1. All screening labs should be performed within 14 days of treatment initiation.
• Female participant of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving the 1st dose of study medication.

You may not qualify if:

• Has a known driver mutation associated with lack of cemiplimab efficacy (e.g. EGFR, ALK, HER2, RET or ROS1). Patients with smoking-related targetable driver mutation (e.g. KRAS or BRAF non-V600E) are eligible for this study. If this is unavailable, a patient should have smoked ≥10 packyears to be eligible.
• Has a known mutation in STK11 and/or KEAP1 predictive of poor response to PD-(L)1 inhibitors.
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the 1st dose of treatment.
• Has received prior therapy with any antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways other than PD-(L)1 blockade, e.g. anti-CD137 or a CTLA-4 antibody.
• Has a known additional malignancy that is progressing or requires active treatment.
• Has evidence of symptomatic interstitial lung disease or an active, non-infectious pneumonitis.
• Presence of cardiovascular disease, as defined by:
• New York Heart Association heart failure classifications of Class II, III or IV; or myocardial infarction, or acute coronary syndrome within 12 months of first dose of study medication or
• Transient ischemic attack or stroke within 1 year
• Any condition that requires ongoing/continuous corticosteroid therapy (\>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study medication. Participants who require a brief course of steroids (up to 2 days in the week before enrollment) or physiologic replacement are not excluded.
• Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments.
• Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication.
• Uncontrolled infection with known HIV, hepatitis B or hepatitis C infection, diagnosis of immunodeficiency, and/or tuberculosis (active or latent).
• Participants with known controlled HIV infection (undetectable viral load on HIV RNA PCR) and CD4 count above 350 either spontaneously or on a stable antiviral regimen are eligible. For these participants monitoring will be performed per local standards.
• Participants with HBsAg positive who have controlled infection (serum HBV DNA PCR that is below the limit of detection and receiving anti-viral therapy for hepatitis B) are eligible. Participants with controlled infections must undergo periodic monitoring of HBV DNA. Participants must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study medication.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Regeneron Pharmaceuticals: collaborator
• Leiden University Medical Center: collaborator

Study Sites (2)

Netherlands Cancer Institute - Antoni van Leeuwenhoek

Amsterdam, 1066 CX, Netherlands

Location

Leids Universitair Medisch Centrum (LUMC)

Leiden, 2333 ZA, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Dr. W.S.M.E. Theelen, MD PhD

CONTACT

0031 020 512 9111.; w.theelen@nki.nl

Eline R Harding, MD

CONTACT

0031 020 512 9111.; e.harding@NKI.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2026
• First Posted: September 8, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: September 8, 2026

Record last verified: 2026-09

Locations

NL (2)