Immunotherapy + Radiotherapy for Non-Small Cell Lung Cancer

(TRIPL Trial)

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

Trial Summary

What is the purpose of this trial?

Determine anti-tumor efficacy by characterizing response rates on positron emission tomography (PET) following three cycles of induction immunotherapy with cemiplimab and fianlimab without chemotherapy for locally advanced non-small cell lung cancer (LA-NSCLC).

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.

What data supports the effectiveness of the treatment combining immunotherapy and radiotherapy for non-small cell lung cancer?

Research shows that combining radiotherapy with immunotherapy can improve treatment outcomes by boosting the immune system's ability to fight cancer cells. In a study with a similar approach, adding an immune checkpoint inhibitor to radiotherapy showed early positive responses in some patients with non-small cell lung cancer. ^{1 2 3 4 5}

Is the combination of immunotherapy and radiotherapy safe for treating non-small cell lung cancer?

Immunotherapy treatments like cemiplimab can cause immune-related side effects, such as colitis (inflammation of the colon), which may be more common with certain drugs. These side effects are important to consider when evaluating the safety of these treatments. ^{6 7 8 9 10}

How is the treatment of Cemiplimab and Fianlimab with radiotherapy unique for non-small cell lung cancer?

This treatment combines immunotherapy drugs Cemiplimab and Fianlimab with radiotherapy, which is unique because it leverages the immune system to target cancer cells while also using radiation to directly attack the tumor. This dual approach may enhance the overall effectiveness compared to using either method alone. ^{2 4 11 12 13}

Research Team

Nitin Ohri, MD, MS

Principal Investigator

Albert Einstein College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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

Findings from Research

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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. [2022]

2. Singapore pubmed.ncbi.nlm.nih.gov

Famitinib enhances the antitumor effect of radioimmunotherapy in murine lung cancer. [2023]

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Radiation therapy and immunotherapy: what is the optimal timing or sequencing? [2019]

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Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. [2023]

5. Ireland pubmed.ncbi.nlm.nih.gov

Radiotherapy to reinvigorate immunotherapy activity after acquired resistance in metastatic non-small-cell lung cancer: A pooled analysis of two institutions prospective phase II single arm trials. [2023]

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Association of Immune-Related Adverse Events and Efficacy Outcomes With Consolidation Pembrolizumab After Chemoradiation in Patients With Inoperable Stage III Non-Small-Cell Lung Cancer. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Immune-Related Adverse Events Predict the Efficacy of Immune Checkpoint Inhibitors in Lung Cancer Patients: A Meta-Analysis. [2022]

8. United States 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. [2021]

9. Spain pubmed.ncbi.nlm.nih.gov

Predictors of immune-related adverse events and outcomes in patients with NSCLC treated with immune-checkpoint inhibitors. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Immune-Related Toxicity in Non-small cell Lung Cancer: Current State-of-The-Art and Emerging Clinical Challenges. [2023]

11. United States 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. [2015]

12. United States 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. [2021]

13. England 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. [2020]