Radiation + Immunotherapy for Non-Small Cell Lung Cancer

Recruiting at 187 trial locations

Overseen By Megan E. Daly

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Immunotherapy

Must not be taking: Tyrosine inhibitors, Steroids

Disqualifiers: Auto-immune disease, Pneumonitis, Hepatitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 24 months

427 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding radiation therapy to the usual treatment of immunotherapy, with or without chemotherapy, can help manage advanced non-small cell lung cancer that has spread and is PD-L1 negative (a specific cancer marker). The study seeks to discover if this combination can halt cancer growth and possibly extend patients' lives. Participants should have advanced non-small cell lung cancer that hasn't responded well to standard treatments and must have a PD-L1 negative status on their tumors.

As a Phase 2 and Phase 3 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group and is in the final step before FDA approval. It offers patients a chance to contribute to potentially groundbreaking advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take systemic immunostimulatory or immunosuppressive drugs, including more than 10 mg of prednisone per day, within two weeks before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that the treatments in this trial, including nivolumab, ipilimumab, and stereotactic body radiation therapy (SBRT), have been studied for safety in people with non-small cell lung cancer. Nivolumab, for instance, has a safety record that includes some serious side effects such as pneumonia and breathing problems, occurring in less than 2% of patients.

When used with nivolumab, ipilimumab has a safety profile similar to other drug combinations in everyday medical practice, as studies indicate. Common side effects may include tiredness and skin issues, but these are usually manageable.

SBRT, a precise radiation treatment, has been used safely in early-stage lung cancer patients who cannot undergo surgery. It is generally well-tolerated, though there is a risk of side effects, such as short-term tiredness or inflammation in the treated area.

Overall, while any treatment carries risks, these therapies have been tested, and the side effects are often known and treatable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-small cell lung cancer because they combine radiation with immunotherapy, potentially enhancing the body's immune response against cancer cells more effectively than current treatments. Unlike standard chemotherapy, which directly targets and kills cancer cells, these experimental treatments utilize drugs like nivolumab and pembrolizumab to stimulate the immune system, possibly leading to more durable responses. Additionally, combining immunotherapy with radiation may improve the treatment's effectiveness by making cancer cells more susceptible to being attacked by the immune system. This approach could offer new hope for patients by potentially increasing treatment efficacy and survival rates.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that combining radiation therapy with immunotherapy can help treat non-small cell lung cancer (NSCLC). In this trial, participants in Arm A will receive immunotherapy, including nivolumab and ipilimumab, with or without chemotherapy. Studies have found that patients with advanced NSCLC who received nivolumab and ipilimumab lived longer than those who only had chemotherapy. Nivolumab, often used with ipilimumab, has demonstrated lasting positive effects in many patients with advanced NSCLC. Participants in Arm B will receive a combination of immunotherapy, with or without chemotherapy, and stereotactic body radiation therapy. This focused radiation effectively shrinks tumors with manageable side effects. These treatments work together to enhance the body's ability to fight cancer and control tumor growth. ^{1 6 7 8 9}

Who Is on the Research Team?

Christine M Bestvina

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

Adults with advanced non-small cell lung cancer that's spread and is PD-L1 negative can join. They shouldn't have had chemotherapy or immunotherapy for metastatic NSCLC, no recent pneumonitis, no active infections or serious heart conditions, and must not be pregnant. Prior therapy for non-metastatic disease is okay if it ended over 6 months ago.

Inclusion Criteria

I am able to care for myself and perform daily activities.

I haven't taken strong immune system drugs or more than 10 mg of steroids daily in the last 2 weeks.

I don't have any serious illnesses that would stop me from following the study's requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive nivolumab and ipilimumab intravenously every 6 weeks for up to 24 months, with or without radiation therapy

24 months

Every 6 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Every 3 months for 3 years, then every 6 months for 2 years (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Nab-paclitaxel
• Nivolumab
• Paclitaxel
• Pembrolizumab
• Pemetrexed
• Stereotactic Body Radiation Therapy

Trial Overview The trial tests adding radiation to usual treatments (immunotherapy with/without chemo) in stage IV lung cancer patients who are PD-L1 negative. It compares the effects of this combination against usual treatment alone on tumor growth and patient survival.

How Is the Trial Designed?

Group I: Arm B (immunotherapy, +/- chemotherapy, radiation therapy) Experimental Treatment 10 Interventions

Patients receive 1 of 6 treatment options as in Arm A. Patients also undergo 3 fractions of radiation therapy every other day. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening.

Group II: Arm A (immunotherapy, +/- chemotherapy) Experimental Treatment 9 Interventions

Patients receive nivolumab intravenously (IV) over 30 minutes on days 1 and 22 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity or patients may receive standard of care systemic immunotherapy. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The maximum tolerated dose (MTD) and recommended dose (RD) of nab-paclitaxel plus carboplatin, combined with thoracic radiotherapy, was determined to be at level 3 (80 mg/m2 of nab-paclitaxel and 2 mg/ml/min of carboplatin), with no significant pulmonary toxicities observed.

The treatment regimen was well tolerated, with 71.4% of patients showing an objective response, indicating its potential efficacy for patients with locally advanced non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of nab-paclitaxel plus carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small cell lung cancer. Kaira, K., Tomizawa, Y., Imai, H., et al.[2017]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In a study involving 180 patients with advanced non-small cell lung cancer (NSCLC), pemetrexed-carboplatin did not show superior efficacy compared to paclitaxel-carboplatin, with similar progression-free survival (PFS) rates and overall survival after a median follow-up of 17 months.

While both treatment regimens had comparable overall toxicities, the paclitaxel-carboplatin group experienced higher rates of alopecia and peripheral neuropathy, indicating a difference in side effects between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open-Label Randomized Controlled Trial Comparing the Efficacy and Safety of Pemetrexed-Carboplatin versus (Weekly) Paclitaxel-Carboplatin as First-Line Chemotherapy in Advanced Non-Squamous Non-Small Cell Lung Cancer. Yadav, A., Malik, PS., Khurana, S., et al.[2021]

In a phase II trial involving 32 elderly patients with untreated advanced non-small cell lung cancer, the combination of weekly nanoparticle albumin-bound-paclitaxel and carboplatin showed a 50% overall response rate and a median overall survival of 17.5 months, indicating significant efficacy.

The treatment was well tolerated, with no treatment-related deaths or febrile neutropenia reported, and it resulted in less neuropathic toxicity compared to traditional regimens, making it a promising option for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Modified Carboplatin Plus Weekly Nab-Paclitaxel in Elderly Patients with Non-Small Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 1301. Miyauchi, E., Inoue, A., Usui, K., et al.[2018]

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

In a phase III trial involving 1,052 patients with advanced non-small-cell lung cancer, nab-paclitaxel plus carboplatin showed a significantly higher overall response rate (33%) compared to solvent-based paclitaxel plus carboplatin (25%), indicating greater efficacy in treatment.

Nab-paclitaxel was associated with fewer severe side effects, such as neuropathy and neutropenia, compared to solvent-based paclitaxel, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. Socinski, MA., Bondarenko, I., Karaseva, NA., et al.[2022]

In a study of 40 patients with stage III/IV squamous non-small-cell lung cancer, the combination of nab-paclitaxel and a platinum agent (cisplatin or carboplatin) resulted in a high overall response rate of 62.5% and a disease control rate of 92.5%, indicating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse effects being mild to moderate (grade 1 to 2), including myelosuppression and gastrointestinal issues, suggesting that nab-paclitaxel combined with platinum agents is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical investigation of efficacy of albumin bound paclitaxel plus platinum compounds as first-line chemotherapy for stage III/IV squamous non-small cell lung cancer. Fang, Y., Wang, L., Xia, GH., et al.[2022]

In a Phase 2 study involving 29 patients with advanced non-small cell lung cancer (NSCLC) who had previously failed PD-(L)1 inhibitor treatment, nab-paclitaxel demonstrated a promising objective response rate (ORR) of 55.2%, indicating its efficacy as a subsequent treatment option.

The treatment was associated with manageable safety profiles, with significant toxicities including leukopenia (27.6%) and neutropenia (31.0%), suggesting that while nab-paclitaxel is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial. Sonoda, T., Umeda, Y., Demura, Y., et al.[2023]

The combination of pemetrexed and nab-paclitaxel was found to be feasible and well tolerated in patients with advanced non-small cell lung cancer (NSCLC), with a recommended phase II dose established at pemetrexed 500 mg/m² and nab-paclitaxel 260 mg/m².

In a phase II trial involving 37 patients, the treatment showed a response rate of 14% and a disease control rate of 46%, with a median overall survival of 8.8 months, indicating some efficacy in second and third-line therapy despite the early closure of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer. Ho, C., Davies, AM., Sangha, RS., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1910231

Nivolumab plus Ipilimumab in Advanced Non–Small-Cell ... First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01503

Five-Year Survival Outcomes With Nivolumab Plus ... Patients with metastatic non–small-cell lung cancer (mNSCLC) have historically had a poor prognosis, with a 5-year survival rate of 7%.

3. esmoopen.com esmoopen.com/article/S2059-7029(25)00992-5/fulltext

final, 6-year outcomes from CheckMate 9LA Six-year OS rates in patients with squamous or non-squamous NSCLC were 14% versus 5% and 17% versus 12%, respectively (Figure 1D and E). Higher ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3296082/

Ipilimumab: its potential in non-small cell lung cancer - PMC Ipilimumab showed promising results in a first-line NSCLC phase II study combining carboplatin/paclitaxel chemotherapy with concurrent or phased ipilimumab.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1525730425000099

Comparative Effectiveness of Nivolumab and Ipilimumab ... This study aimed to compare the treatment response and real-world outcomes of NIC with the current standard of care pembrolizumab plus chemotherapy (PC) in PD- ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38240151/

Real-world safety of first-line immuno-oncology ... These results show that in a real-world setting, NIVO + IPI-based regimens have similar safety to other IO + chemotherapy combinations when used as a first ...

7. jto.org jto.org/article/S1556-0864(22)01556-8/fulltext

Safety of First-Line Nivolumab Plus Ipilimumab in Patients ... We characterized the safety of first-line nivolumab plus ipilimumab (NIVO+IPI) in a large patient population with metastatic NSCLC and ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2059702925009925

Nivolumab plus ipilimumab with chemotherapy as first-line ... The phase III CheckMate 9LA study demonstrated durable overall survival (OS) benefit with nivolumab plus ipilimumab with chemotherapy versus chemotherapy in ...

9. tandfonline.com tandfonline.com/doi/full/10.2217/fon-2023-0612

Full article: Real-world safety of first-line immuno-oncology ... Aim: Real-world adverse event (AE) data are limited for first-line (1L) treatments in advanced non-small-cell lung cancer (NSCLC).