Nivolumab + Radiation Therapy +/- Ipilimumab for Brain Metastasis from Lung Cancer

Overseen By Jing Li

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti PD1, Anti PD-L1

Disqualifiers: Autoimmune disease, Active infection, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 32

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of different treatment combinations for individuals with non-small cell lung cancer that has spread to the brain. It tests the effects of the drugs nivolumab (Opdivo) and ipilimumab (Yervoy), monoclonal antibodies that may slow or stop cancer cell growth, in combination with types of radiation therapy. Participants will receive one of four treatment plans, involving these drugs and either stereotactic radiosurgery (a precise, high-dose radiation treatment) or whole-brain radiation therapy. Suitable candidates have non-small cell lung cancer with brain metastases visible on MRI and at least one brain lesion treatable with radiation. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this combination of therapies.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on certain investigational drugs or have recently received specific treatments, you may need to wait before joining. It's best to discuss your current medications with the trial team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining nivolumab with stereotactic radiosurgery (SRS), a precise brain radiation technique, is safe for patients with brain tumors from lung cancer. Studies have found that this treatment does not cause radiation necrosis, which damages healthy brain tissue. Patients generally tolerate the combination of nivolumab, ipilimumab, and SRS well without serious problems.

Nivolumab has also been tested with whole-brain radiotherapy (WBRT) for safety. Current evidence suggests that using drugs like nivolumab with brain radiation is safe and might improve patient outcomes. The combination of nivolumab and ipilimumab with WBRT has shown no new safety issues, making it a promising treatment option.

Overall, these treatments appear well-tolerated according to available studies. However, since this trial is still in its early stages, ongoing monitoring remains important to fully understand the safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for brain metastasis from lung cancer because they combine innovative immunotherapy drugs, nivolumab and ipilimumab, with radiation therapy. Unlike traditional treatments that primarily involve chemotherapy and radiation, nivolumab and ipilimumab are immune checkpoint inhibitors that help the immune system recognize and attack cancer cells more effectively. This approach could potentially enhance the body's natural defenses against tumors. Additionally, the integration of stereotactic radiosurgery (SRS) or whole-brain radiation therapy (WBRT) with these drugs might improve outcomes by precisely targeting brain lesions while boosting immune response, offering a promising alternative to existing options.

What evidence suggests that this trial's treatments could be effective for brain metastasis from lung cancer?

This trial will evaluate different combinations of treatments for brain metastasis from lung cancer. Research has shown that using nivolumab with stereotactic radiosurgery (SRS), a precise radiation treatment, looks promising for treating brain tumors that have spread from lung cancer. Studies have found that this combination is safe and may help control tumor growth. In this trial, some participants will receive nivolumab with SRS, while others will receive nivolumab with ipilimumab and SRS. Early results suggest better outcomes for patients with non-small cell lung cancer and brain tumors. Additionally, this trial will test nivolumab with whole-brain radiotherapy (WBRT), which might improve patient outcomes more than radiation alone. Another group will receive nivolumab and ipilimumab with WBRT, a combination that has also shown positive results, offering hope for better management of brain tumors. ^{1 2 5 6 7}

Who Is on the Research Team?

Jing Li

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with non-small cell lung cancer that has spread to the brain. They must have at least one treatable brain lesion, be in good physical condition (ECOG 0 or 1), and meet certain blood and biochemical criteria. Women of childbearing age need a negative pregnancy test and agree to birth control; men must use contraception too. Those who've had prior treatments may qualify under specific conditions.

Inclusion Criteria

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

I am not pregnant and agree to use birth control.

My cancer has spread to my brain, as confirmed by an MRI.

Exclusion Criteria

I have been diagnosed with a severe active form of scleroderma, lupus, or another similar autoimmune disease.

I am not using high-dose dexamethasone, do not have specific tumor mutations, am not allergic to study drugs, and have not had recent CNS surgery.

I have recently used monoclonal antibodies or anti PD1/PD-L1 therapies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab with stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT), with or without ipilimumab, depending on the group assignment.

6-8 weeks

Nivolumab every 2 weeks, ipilimumab every 6 weeks, SRS once, WBRT daily for 10 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Follow-up at 30 days, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Stereotactic Radiosurgery
• Whole-Brain Radiotherapy

Trial Overview The study is testing how well patients respond to Nivolumab combined with either stereotactic radiosurgery or whole-brain radiotherapy, with or without Ipilimumab. It aims to find the safest doses while assessing how these therapies affect tumor growth in the brain from lung cancer.

How Is the Trial Designed?

Group I: Group D (nivolumab, ipilimumab, WBRT) Experimental Treatment 5 Interventions

GROUP D: Patients receive nivolumab as in Group A and ipilimumab as in Group C. Patients undergo WBRT once daily for 10 days.

Group II: Group C (nivolumab, ipilimumab, SRS) Experimental Treatment 5 Interventions

Patients receive nivolumab as in Group A and ipilimumab IV over 90 minutes every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo SRS once the day after nivolumab administration.

Group III: Group B (nivolumab, WBRT) Experimental Treatment 4 Interventions

Patients then receive nivolumab as in Group A. Patients undergo WBRT once daily for 10 days.

Group IV: Group A (nivolumab, SRS) Experimental Treatment 4 Interventions

Patients receive nivolumab IV over 90 minutes every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo SRS once the day after nivolumab administration.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10335483/

Nivolumab and ipilimumab with concurrent stereotactic ... Concurrent brain SRS with nivolumab/ipilimumab was safe for patients with active NSCLC BM. Preliminary analyses of treatment efficacy were ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37402581/

analysis of the safety cohort for non-randomized, open-label ... Concurrent brain SRS with nivolumab/ipilimumab was safe for patients with active NSCLC BM. Preliminary analyses of treatment efficacy were encouraging for ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301623082342

Long-Term Intracranial Outcomes With Combination Dual ... Dual ICPI plus SRS appears to be an effective treatment option for patients with NSCLC and melanoma brain metastases, including those with symptomatic disease.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.2531

Concurrent nivolumab and ipilimumab with brain ... Concurrent SRS withnivo/ipi was safe for pts with active NSCLC brain mets. Preliminary analyses of efficacy were encouraging for durable intracranial and ...

5. jto.org jto.org/article/S1556-0864(23)00525-7/fulltext

Systemic and Intracranial Outcomes With First-Line ... Systemic and intracranial outcomes with first-line nivolumab plus ipilimumab in patients with metastatic NSCLC and baseline brain metastases.

6. jto.org jto.org/article/S1556-0864(25)01227-4/fulltext

MA10.05 Phase I/II Study of Nivolumab and Ipilimumab ... Patients received brain SRS alongside systemic therapy with nivolumab and ipilimumab within a 7-day window. The primary endpoints were safety and intracranial ...

7. redjournal.org redjournal.org/article/S0360-3016(18)32232-6/pdf

Safety and Clinical Outcomes of Ipilimumab and ... Purpose/Objective(s): Retrospective reports have suggested up-front stereotactic radiosurgery (SRS) to be a potentially effective treatment option for brain ...