Pembrolizumab + Radiation Therapy for Non-Small Cell Lung Cancer

Palo Alto (17 mi)

James W. Welsh | MD Anderson Cancer Center

Overseen byJames Welsh

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: M.D. Anderson Cancer Center

No Placebo Group

Breakthrough Therapy

Approved in 3 jurisdictions

Trial Summary

What is the purpose of this trial?This randomized phase I/II trial studies the side effects and best dose of pembrolizumab when given together with stereotactic body radiation therapy or non-stereotactic wide-field radiation therapy (conventional radiation therapy) and to see how well they work in treating patients with non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving pembrolizumab together with radiation therapy may kill more tumor cells.

Eligibility Criteria

This trial is for adults with non-small cell lung cancer, including those with Stage IV metastatic disease. Participants must have at least one measurable tumor and be in good physical condition (ECOG 0 or 1). They should not be pregnant or breastfeeding, agree to use contraception, and meet specific blood criteria. Those with brain metastases can join under certain conditions but cannot have autoimmune diseases, recent monoclonal antibody treatments, or other disqualifying medical issues.

Inclusion Criteria

I have a tumor in my chest or liver that can be treated with radiation.

My cancer is confirmed to be non-small cell lung cancer or, for specific cases, any solid tumor type.

I am not pregnant and will use birth control during the trial.

I am fully active or restricted in physically strenuous activity but can do light work.

I have more than one cancer lesion, and they can be seen on scans.

Exclusion Criteria

I have recently received a live vaccine.

I have an immune system disorder or I'm taking steroids.

I have been diagnosed with an active autoimmune disease like scleroderma or lupus.

I have had radiation therapy for all cancer spots in my chest and liver.

I have a history of HIV or active hepatitis B or C.

I've had severe side effects from previous cancer treatments.

I have brain metastasis causing symptoms.

Treatment Details

The trial is testing the combination of Pembrolizumab (an immunotherapy drug) with different types of radiation therapy: Stereotactic Body Radiation Therapy which targets tumors precisely over fewer sessions, or conventional wide-field radiation therapy. The goal is to determine the best dose and effectiveness in shrinking tumors by enhancing the body's immune response against cancer cells.

7Treatment groups

Experimental Treatment

Group I: Group V, Phase II (low dose radiation therapy)Experimental Treatment7 Interventions

Patients with lesions amenable to SBRT or WFRT receive pembrolizumab IV as in Group I. Patients also receive either IMRT, PBRT, or 3D-CRT in 15 fractions to the primary lesions and low dose radiation therapy to other lesions on days 43-61 or SBRT in 4 fractions to primary lesions and low dose radiation therapy to other lesions on days 44-47.

Group II: Group IV, Phase II (pembrolizumab + XRT upon PD)Experimental Treatment5 Interventions

Patients who exhibit a lung lesion with size and location not amenable to SBRT, but amenable to WFRT receive pembrolizumab IV as in Group I without XRT. The decision on when to start XRT will be assessed first at week 5 (after the second dose of pembrolizumab). If a patient has PD based on irRC then XRT will be delivered after the third dose of pembrolizumab, while patients with SD or PR will not start XRT and will continue to be followed. These patients will then have follow up CT scans 5 weeks after course 3 and then approximately every 3 months for the remainder of the trial; any patient at this point with PD will then have XRT delivered with the sixth dose of pembrolizumab.

Group III: Group III, Phase II (pembrolizumab + IMRT, PBRT, or 3D-CRT)Experimental Treatment4 Interventions

Patients who exhibit a lung lesion with size and location not amenable to SBRT, but amenable to WFRT receive pembrolizumab IV as in Group I and IMRT, PBRT, or 3D-CRT on days 43-61.

Group IV: Group II, Phase II (pembrolizumab + XRT upon PD)Experimental Treatment6 Interventions

Patients who exhibit a lung lesion with size and location amenable to SBRT receive pembrolizumab IV as in Group I without XRT. At the first planned efficacy evaluation (5 weeks), patients exhibiting PD are treated with SBRT concurrent with the remaining cycles of pembrolizumab. In the event that lesion size has progressed to the point where the attending physician no longer considers SBRT safe, then the patient will be salvaged with IMRT, PBRT, or 3D-CRT and analyzed as part of the fourth treatment group.

Group V: Group II, Phase I (pembrolizumab + IMRT, PBRT or 3D-CRT)Experimental Treatment5 Interventions

Patients who exhibit a lung lesion of size or location not amenable to SBRT, but amenable to WFRT receive pembrolizumab as in Group I and either IMRT, PBRT, or 3D-CRT in 15 fractions total on days 1-19 concurrent with pembrolizumab administration.

Group VI: Group I, Phase II (pembrolizumab + SBRT)Experimental Treatment3 Interventions

Patients who exhibit a lung lesion with size and location amenable to SBRT receive pembrolizumab IV on day 1 and SBRT on days 44-47 or IMRT, PBT, or 3D-CRT on days 43-61. Treatment with pembrolizumab repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.

Group VII: Group I, Phase I (pembrolizumab + SBRT)Experimental Treatment6 Interventions

Patients who exhibit a lung lesion of size and location amenable to SBRT receive pembrolizumab IV over 30 minutes on day 1. Patients also receive SBRT in 4 fractions daily on days 2-5 or either IMRT, PBRT, or 3D-CRT in 15 fractions total concurrent with pembrolizumab administration on days 1-19. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

🇺🇸 Approved in United States as KEYTRUDA for: