A Study Evaluating The Combination of Immunotherapy With Radiotherapy in Non-Small Cell Lung Cancer
A Randomized Phase II Study of Radiotherapy Plus Immune Checkpoint Inhibitor Therapy Versus Standard of Care Chemotherapy in Patients With Metastatic or Relapsed Non-Small Cell Lung Cancer Previously Treated With Immunotherapy
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests immunotherapy, which helps the immune system fight cancer, together with radiation treatment. It is for adults with non-small cell lung cancer that has spread or come back and has gotten worse after prior immunotherapy.
Current clinical trials testing the combination of immunotherapy with radiotherapy.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be age 18 or older, with non-small cell lung cancer confirmed by a tissue or cell test.
- Have cancer that has spread or come back and worsened after exactly one prior course of anti-PD-1 or anti-PD-L1 immunotherapy. Special timing rules apply to treatment given for earlier-stage cancer.
- Have cancer that can be measured on a CT or MRI scan and at least one tumor that meets the study’s size and location rules for focused, high-dose radiation.
- Be able to care for yourself and be out of bed for at least half the day. Be eligible for standard immunotherapy or chemotherapy and able to safely receive the study treatments.
- If your cancer has BRAF, KRAS, or MET gene changes that can be targeted with drugs, have already received at least one suitable targeted treatment as well as immunotherapy.
- Cancer in the brain or its lining is allowed if your doctor says it does not need immediate treatment and likely will not need it during the first treatment cycle. Other cancers are allowed if they will not affect study safety or results.
- Agree to use birth control, if applicable, before and during the study and for 3 months after treatment ends.
- Be able to understand the study and sign a consent form.
Who can't join
- Cancer with certain EGFR, ALK, ROS1, RET, NTRK, or HER2 gene changes.
- Past lung inflammation not caused by infection that needed steroid treatment.
- Interstitial lung disease, which can cause lung scarring or inflammation.
- An illness that is not under control.
- Pregnancy. Breastfeeding must stop during study participation.
- Past radiation to a planned treatment site with more than 10% dose overlap.
- Tumor directly involving the food pipe, stomach, small bowel, or colon, unless safe radiation dose limits can be met.
- Tumors where focused, high-dose radiation cannot be given safely, including tumor near the spinal cord with less than 3 mm of space from the cord.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: * 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: * If patient received neoadjuvant, adjuvant, or consolidation anti-PD-1/PD-L1 therapy for Stage I-III disease and progressed ≤365 days from initiation (Cycle 1 Day 1), this counts as the single allowed therapy for advanced disease * If patient progressed \>365 days from neoadjuvant/adjuvant therapy initiation, this does NOT count as therapy for advanced disease, and patient must have received subsequent anti-PD-1/PD-L1 therapy for Stage IV or recurrent disease * Patients with the following sensitizing mutations are ineligible, given known poor response to immunotherapy: EGFR, ALK, ROS1, RET, NTRK, HER2. * Patients with the following sensitizing mutations must have previously received at least one of the appropriate targeted therapies, in addition to prior immunotherapy: BRAF, KRAS, MET. Prior targeted therapy for participants with targetable alterations is allowed if all other eligibility criteria is also met. * Clinical/Laboratory Criteria * Age ≥18 years * ECOG Performance Status 0-2 (see Appendix A) * Participants must be able to safely receive the investigational drug combination and the investigator's choice of standard of care regimens described in Section 5.1 (Agent Administration), per the current FDA-approved package inserts, treating investigator's discretion, and institutional guidelines. * Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy. * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * Because radiation and chemotherapy are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Both men and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of immunotherapy, radiation, and/or chemotherapy administration. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * 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. Radiation-Specific Exclusions * 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
Study sites (1)
IL
- o University of Chicago Medicine Comprehensive Cancer Center · Chicago, IL 60637Clinical Trials Intake · Study contact · 1-855-702-8222 · cancerclinicaltrials@bsd.uchicago.eduAditya Juloori · Principal investigatorMore trials in Chicago