Immunotherapy + Radiotherapy for Non-Small Cell Lung Cancer

(TRIPL Trial)

Recruiting at 1 trial location

Overseen By Nitin Ohri, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Albert Einstein College of Medicine

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: EGFR/ALK mutations, Pneumonitis, Myocarditis, 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: 16

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a combination of two immunotherapy drugs, cemiplimab and fianlimab, can shrink tumors in people with non-small cell lung cancer. The goal is to evaluate these drugs without the usual chemotherapy. People diagnosed with this type of lung cancer who have not yet received any treatment may be good candidates for the trial. Participants must have a measurable tumor visible on a PET scan and be eligible for non-surgical treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss your specific 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 the combination of cemiplimab and fianlimab is generally safe, as previous studies have indicated. Most patients tolerated the treatment well. Earlier studies with these drugs, both separately and together, reported side effects similar to those of other drugs in this category.

Common side effects may include tiredness, skin rash, or diarrhea. Serious side effects were less common but did occur in some cases. Cemiplimab alone has been used to treat non-small cell lung cancer with good results, suggesting that adding fianlimab builds on a treatment already considered relatively safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Cemiplimab and Fianlimab for non-small cell lung cancer because it offers a fresh approach by combining immunotherapy with radiotherapy. Unlike traditional treatments that primarily involve chemotherapy or singular immunotherapy agents, this combo targets both the immune system and the cancer cells more directly. Cemiplimab and Fianlimab work by blocking specific proteins that usually help cancer cells hide from the immune system, potentially leading to a stronger immune response against the cancer. Additionally, the use of a fixed-dose combination simplifies treatment administration and might improve patient compliance compared to more complex regimens. This innovative approach could offer a more effective option for patients, especially those with lower PD-L1 expression, who often have fewer treatment choices.

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

Research has shown that using cemiplimab and fianlimab together yields promising results for treating non-small cell lung cancer (NSCLC). This trial will evaluate this combination in different cohorts. In Cohort 1, participants with PD-L1 (TPS ≥ 50%) will receive a fixed-dose combination of cemiplimab and fianlimab, followed by radiotherapy. In Cohort 2, participants with PD-L1 (TPS < 50%) will receive the same combination along with histology-specific platinum-doublet chemotherapy and radiotherapy. Earlier studies have demonstrated more than 60% response rates in patients. Cemiplimab helps the immune system recognize and attack cancer cells, while fianlimab enhances the immune response through a different pathway. Both treatments aim to strengthen the body's natural defenses to fight the tumor more effectively. Overall, early studies suggest that this combination could be a powerful option for NSCLC patients. ^{2 3 6 7 8}

Who Is on the Research Team?

Nitin Ohri, MD, MS

Principal Investigator

Albert Einstein College of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals with locally advanced non-small cell lung cancer. Participants should not have received prior treatments for their condition and must be suitable candidates for immunotherapy and radiotherapy.

Inclusion Criteria

My lung cancer is confirmed by biopsy, untreated, measurable, and at a specific stage.

My cancer's PD-L1 status was tested before treatment.

I can take care of myself and am up and about more than half of the day.

Exclusion Criteria

Known psychiatric or substance abuse disorders

Current or recent participation in investigational studies

Specific medical history exclusions

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Immunotherapy

Three cycles of induction immunotherapy with cemiplimab and fianlimab, with histology-specific platinum doublet chemotherapy added for subjects with PD-L1 TPS <50%

9 weeks

3 visits (in-person)

Radiotherapy

Thoracic radiotherapy with concurrent platinum doublet chemotherapy recommended for subjects with PD-L1 TPS <50%

4-6 weeks

Consolidation Immunotherapy

13 cycles of consolidation immunotherapy with cemiplimab and fianlimab, starting 4-6 weeks after completion of radiotherapy

39 weeks

13 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• Fianlimab
• Radiotherapy

Trial Overview The study tests the effectiveness of two immune checkpoint inhibitors, Fianlimab and Cemiplimab, combined with radiotherapy in treating LA-NSCLC. It measures how well tumors respond without using chemotherapy.

How Is the Trial Designed?

Group I: Cohort 2: PD-L1 (TPS < 50%) Experimental Treatment 4 Interventions

* FDC of Cemiplimab 350mg IV + Fianlimab 1600mg IV and histology-specific platinum-doublet chemotherapy (PDC) every 3 weeks x 3 cycles * Radiotherapy +/- PDC * FDC of Cemiplimab + Fianlimab every 3 weeks x 13 cycles, starting 4-6 weeks after completion of RT Weekly radiosensitizing PDC will be recommended for PD-L1 TPS \<50% patients during RT but is not required

Group II: Cohort 1: PD-L1 (TPS ≥ 50%) Experimental Treatment 3 Interventions

* Fixed-dose combination (FDC) of Cemiplimab 350mg IV + Fianlimab 1600mg IV every 3 weeks x 3 cycles * Radiotherapy * FDC of Cemiplimab + Fianlimab every 3 weeks x 13 cycles, starting 4-6 weeks after completion of RT

Who Is Running the Clinical Trial?

Albert Einstein College of Medicine

Lead Sponsor

Trials

302

Recruited

11,690,000+

Nitin Ohri

Lead Sponsor

Trials

1

Recruited

5+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Henry Ford Health System

Collaborator

Trials

334

Recruited

2,197,000+

NYU Langone Health

Collaborator

Trials

1,431

Recruited

838,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Published Research Related to This Trial

In a phase I study involving 20 patients with early-stage non-small cell lung cancer, the combination of stereotactic ablative radiotherapy (SABR) and the immune-checkpoint inhibitor atezolizumab was well tolerated, with the maximum tolerated dose established at 1200 mg.

Early efficacy signals were observed, with 17% of patients showing responses after two cycles of atezolizumab before starting SABR, and specific biomarkers indicating T cell activation were found to be predictive of treatment benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. Monjazeb, AM., Daly, ME., Luxardi, G., et al.[2023]

In a pilot study involving 12 patients with metastatic non-small cell lung cancer, the combination of hypofractionated image-guided radiation therapy (HIGRT) and atezolizumab achieved a disease control rate of 50%, with a partial response in 3 patients.

The treatment was associated with a median overall survival of 6.9 months and a median progression-free survival of 2.3 months, with the incidence of grade 3 adverse events being similar to that of atezolizumab alone, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of Atezolizumab Plus Hypofractionated Image Guided Radiation Therapy for the Treatment of Advanced Non-Small Cell Lung Cancer. Qin, A., Rengan, R., Lee, S., et al.[2021]

In a study of 184 patients with non-small cell lung cancer treated with immune checkpoint inhibitors, 26.6% developed immune-related adverse events (IRAEs), with certain factors like statin use and previous corticosteroid therapy increasing the risk of IRAEs.

Interestingly, patients who experienced IRAEs had significantly better progression-free survival (41 weeks vs. 9 weeks) and overall survival (89 weeks vs. 28 weeks), suggesting that the occurrence of IRAEs may be linked to improved treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of immune-related adverse events and outcomes in patients with NSCLC treated with immune-checkpoint inhibitors. Serino, M., Freitas, C., Martins, M., et al.[2022]

Immune checkpoint inhibitors are now a standard treatment for non-small cell lung cancer (NSCLC), but they can cause immune-related adverse events (irAEs), which are unique inflammatory side effects that can complicate treatment.

Recognizing and managing these irAEs is crucial for healthcare providers, as they can lead to severe toxicities that may influence treatment decisions for patients with NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-Related Toxicity in Non-small cell Lung Cancer: Current State-of-The-Art and Emerging Clinical Challenges. O'Leary, CL., Pierce, N., Patel, SP., et al.[2023]

In a phase II trial involving 30 patients with stage III nonsmall cell lung cancer, the combination of intensity-modulated radiation therapy (IMRT) and cetuximab resulted in a 63% overall response rate, indicating significant efficacy in treating this patient population.

The treatment was well-tolerated, with only mild toxicity observed, including a low incidence of grade 3 pneumonitis (3.3%) and overall acute toxicity (36.7%), making it a safe option for elderly patients with multiple health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined treatment of nonsmall cell lung cancer NSCLC stage III with intensity-modulated RT radiotherapy and cetuximab: the NEAR trial. Jensen, AD., Münter, MW., Bischoff, HG., et al.[2015]

The FORCE study is a phase II trial involving 130 patients with stage IV non-squamous non-small cell lung cancer, investigating the effects of nivolumab combined with hypofractionated palliative radiotherapy, aiming to assess its safety and efficacy in improving response rates and survival outcomes.

Preliminary data suggest that combining nivolumab with radiation therapy may enhance immune responses against tumors, potentially leading to better treatment outcomes compared to nivolumab alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fostering efficacy of anti-PD-1-treatment: Nivolumab plus radiotherapy in advanced non-small cell lung cancer - study protocol of the FORCE trial. Bozorgmehr, F., Hommertgen, A., Krisam, J., et al.[2020]

In a meta-analysis of clinical trials, PD-1 inhibitors (like nivolumab and pembrolizumab) were found to have a higher incidence of colitis compared to PD-L1 inhibitors (like atezolizumab and durvalumab), with rates of 1.49% for all grade colitis and 0.85% for grade 3-4 colitis.

The analysis indicated that the relative risk of developing colitis with PD-1 inhibitors was significantly higher (1.80 for all grade colitis and 2.52 for grade 3-4 colitis), suggesting that patients receiving PD-1 inhibitors may need closer monitoring for this adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and Risk of Colitis With Programmed Death 1 Versus Programmed Death Ligand 1 Inhibitors for the Treatment of Cancer. Miyashita, H., Mikami, T., Satoi, S., et al.[2021]

Citations

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A phase 2/3 study of fianlimab, cemiplimab, plus ... Anti–programmed cell death-1 (PD-1) therapies have improved outcomes in patients with NSCLC; however, most patients do not respond or only ...

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Fianlimab (LAG-3 Inhibitor) Combined with Libtayo® ... Our LAG-3 inhibitor fianlimab combined with Libtayo demonstrated greater than 60% response rates. Notably, the safety profile for this combination appears in ...

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P4.11D.09 Fianlimab-Based Combination Therapies in ... Cemiplimab has shown promising clinical efficacy in patients with non-small cell lung cancer (NSCLC) and no actionable mutations, alone (programmed cell death ...