A Study Evaluating The Combination of Immunotherapy With Radiotherapy in Non-Small Cell Lung Cancer

NCT07603856 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: IRB25-1914
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Current clinical trials testing the combination of immunotherapy with radiotherapy.

Conditions

Non-Small Cell Lung Cancer; Metastatic Lung Cancer

Keywords

Radiotherapy; Chemotherapy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  To compare progression-free survival (PFS) in patients with metastatic or relapsed non-small cell lung cancer (mNSCLC) who have progressed after immunotherapy-based treatment, randomized to investigators choice standard of care immunotherapy plus hypofractionated ablative radiotherapy versus investigators' choice of standard of care chemotherapy.

  48 months

Secondary Outcomes (5)

• Overall survival (OS)

  48 months

• Objective response rates (ORR)

  48 months

• Correlation between amount of L1RE1 (LINE1 retrotransposable element 1) and clinical response to treatment

  24 months

• Pharmacodynamic Properties

  24 months

• Safety of Giving Ablative Radiation and Immunotherapy Together

  3 months

Study Arms (2)

Radiotherapy (RT) + Immunotherapy

EXPERIMENTAL

Participants will receive standard immunotherapy of investigator's choice in combination with radiation treatment.

Drug: Investigator Choice Immunotherapy (for example: pembrolizumab, cemiplimab, durvalumab, ipilimumab plus nivolumab); Radiation: Ablative Hypofractionated Radiotherapy

Standard Chemotherapy (Investigator's Choice")

ACTIVE COMPARATOR

Participants will receive standard chemotherapy of investigator's choice.

Drug: Investigator Choice Chemotherapy (for example docetaxel with or without ramucirumab, gemcitabine, or other National Comprehensive Cancer Network (NCCN)-recommended treatments)

Interventions

Investigator Choice Immunotherapy (for example: pembrolizumab, cemiplimab, durvalumab, ipilimumab plus nivolumab) DRUG

Participant will receive an FDA approved immunotherapy according to usual routine practice.

Radiotherapy (RT) + Immunotherapy

Investigator Choice Chemotherapy (for example docetaxel with or without ramucirumab, gemcitabine, or other National Comprehensive Cancer Network (NCCN)-recommended treatments) DRUG

Description something along the lines of Participant will receive an FDA approved chemotherapy according to usual routine practice.

Standard Chemotherapy (Investigator's Choice")

Ablative Hypofractionated Radiotherapy RADIATION

Participant will receive radiotherapy according to usual routine practice.

Radiotherapy (RT) + Immunotherapy

Eligibility Criteria

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

You may qualify if:

• Disease-Related Criteria
• Patients must have histologically or cytologically confirmed metastatic or recurrent non-small cell lung cancer (NSCLC) with progression on prior immunotherapy
• The patient's disease is eligible for SOC treatment with immunotherapy or chemotherapy.
• Patients must have measurable disease per RECIST v1.1, defined as at least one lesion that can be accurately measured in at least one dimension with longest diameter ≥10 mm (or ≥15 mm short axis for lymph nodes) by CT or MRI
• Patients must have at least one lesion that meets criteria for hypofractionated ablative RT treatment:
• Tumor volume 0.25 cc to 65 cc (approximately ≤5 cm maximal dimension)
• Located in sites amenable to ablative RT (see radiotherapy section for specific anatomic criteria)
• Note: Tumors \>65 cc may be partially treated to 65 cc volume
• Prior/Concurrent Therapy Criteria
• Patients must have received exactly ONE prior line of anti-PD-1 or anti-PD-L1 therapy for non-small cell lung cancer. This therapy may have been given as:
• Monotherapy
• In combination with chemotherapy
• In combination with another immunotherapy such as CTLA-4 inhibition
• In combination with a targeted therapy, such as adagrasib
• Special Cases for Neoadjuvant/Adjuvant Immunotherapy:

You may not qualify if:

• Patients with history of (non-infectious) pneumonitis requiring corticosteroids.
• Patients with evidence of interstitial lung disease.
• Patients with uncontrolled intercurrent illness.
• Pregnant women are excluded from this study. Radiation is considered Class X and chemotherapy such as docetaxel are considered Class D agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with radiation, immunotherapy, and chemotherapy breastfeeding should be discontinued if the mother is participating in the study.
• Patients who have received prior radiation to any of the planned treatment sites (\>10% dose overlap)
• Patients with lesions in locations not amenable to safe ablative RT delivery, including:
• Esophagus or stomach directly involved by tumor (unless dose constraints can be met)
• Small bowel or colon directly involved by tumor (unless dose constraints can be met)
• Spinal cord lesions with \<3 mm clearance between epidural disease and spinal cord

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

o University of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

cemiplimab; durvalumab; Ipilimumab; Nivolumab; Ramucirumab; Gemcitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

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

Study Record Dates

• First Submitted: March 9, 2026
• First Posted: May 22, 2026
• Study Start (Estimated): December 12, 2026
• Primary Completion (Estimated): June 25, 2030
• Study Completion (Estimated): June 25, 2030
• Last Updated: May 22, 2026

Record last verified: 2026-05

Locations

US (1)