Immunotherapy Combinations for Lung Cancer

Recruiting at 81 trial locations

Overseen By Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Servier Bio-Innovation LLC

Must not be taking: Steroids, Antibiotics, others

Disqualifiers: Brain metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 2

176 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new combination treatments for individuals with advanced or metastatic non-small cell lung cancer (NSCLC) that hasn't been treated yet. Researchers aim to determine if adding different antibodies (proteins that assist the immune system) to cemiplimab, a type of immunotherapy, can enhance its effectiveness against cancer. The trial will evaluate three different combination treatments to identify the best dose and assess their efficacy. Individuals with advanced NSCLC with high PD-L1 expression who haven't received prior treatment may be eligible for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic chronic steroid therapy or have an active infection requiring antibiotics, you may not be eligible to participate.

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

Research has shown that cemiplimab, a type of medication, is generally safe. In studies for other cancers, some patients experienced serious side effects, but these were mostly manageable. These side effects included low levels of red and white blood cells.

Less information is available about the safety of combinations with S095018, S095024, and S095029. Since this study is in the early stages, researchers are still carefully testing these combinations for safety. Early trials often aim to identify possible side effects and determine the safest dose.

Overall, while cemiplimab is approved for treating some cancers, the new combinations remain under study. Participants should be aware of potential side effects and discuss any concerns with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they utilize a unique approach called immunotherapy, which works by boosting the body's own immune system to fight cancer cells. Unlike traditional treatments like chemotherapy, which directly attack cancer cells but can also harm healthy cells, these investigational drugs—cemiplimab and its combinations with S095018, S095024, and S095029—target specific immune pathways. S095018 is an anti-TIM3 antibody, S095024 is an anti-CD73 antibody, and S095029 is an anti-NKG2A antibody. Each of these combinations aims to block different immune checkpoints, potentially enhancing the immune system's ability to recognize and destroy cancer cells more effectively. This method holds promise for more targeted treatment with potentially fewer side effects.

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

Research has shown that cemiplimab, which participants in this trial may receive in the control arm, works well as a first treatment for advanced non-small cell lung cancer (NSCLC), particularly in patients with high levels of the protein PD-L1. It improved survival rates compared to chemotherapy, with patients living a median of 26.1 months versus 13.3 months. In this trial, other participants will receive combination treatments targeting different ways cancer cells evade the immune system. S095018, S095024, and S095029 are antibodies designed to block these escape routes, potentially making the cancer more visible to the immune system. Early results suggest these combinations might help more patients respond to treatment. This approach aims to enhance cemiplimab's effectiveness by boosting the body’s immune response against cancer cells. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Adults with advanced or metastatic non-small cell lung cancer (NSCLC) that hasn't been treated before can join this trial. They should be in good physical condition, have a certain level of PD-L1 expression in their tumors, and not be candidates for surgery or definitive chemoradiation.

Inclusion Criteria

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

You have a medical condition that can be measured using specific guidelines.

You have given your permission in writing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Combination-therapy safety lead-in

Part A: Determine the recommended dose for expansion (RDE) for S095018, S095024, and S095029 in combination with cemiplimab

6 weeks

2 cycles (each cycle is 21 days)

Randomized dose expansion

Part B: Assess the efficacy of S095018, S095024, or S095029 in combination with cemiplimab

Up to 108 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• S095018
• S095024
• S095029

Trial Overview The study is testing the effectiveness of cemiplimab combined with one of three other drugs: S095018, S095024, or S095029. These combinations are being evaluated to find the safest and most effective doses for treating NSCLC with high PD-L1 expression.

How Is the Trial Designed?

Group I: S095029 (anti-NKG2A antibody) in combination with cemiplimab Experimental Treatment 2 Interventions

Part A: Combination-therapy safety lead-in

Group II: S095029 (anti-NKG2A antibody) RDE in combination with cemiplimab Experimental Treatment 2 Interventions

Part B: Randomized dose expansion

Group III: S095024 (anti-CD73 antibody) in combination with cemiplimab Experimental Treatment 2 Interventions

Part A: Combination-therapy safety lead-in

Group IV: S095024 (anti-CD73 antibody) RDE in combination with cemiplimab Experimental Treatment 2 Interventions

Part B: Randomized dose expansion

Group V: S095018 (anti-TIM3 antibody) in combination with cemiplimab Experimental Treatment 2 Interventions

Part A: Combination-therapy safety lead-in

Group VI: S095018 (anti-TIM3 antibody) RDE in combination with cemiplimab Experimental Treatment 2 Interventions

Part B: Randomized dose expansion

Group VII: Cemiplimab (control arm) Active Control 1 Intervention

Part B: Randomized dose expansion

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

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Servier Bio-Innovation LLC

Lead Sponsor

Trials

9

Recruited

670+

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

Institut de Recherches Internationales Servier

Collaborator

Trials

91

Recruited

67,100+

Published Research Related to This Trial

The combination of platinum-based chemotherapy and immunotherapy is now the standard treatment for patients with metastatic non-small-cell lung cancer, regardless of their programmed death ligand 1 tumor proportion score.

Clinical trials have shown that this combination therapy can lead to improved and long-lasting responses by enhancing the immune system's ability to attack tumors and reducing the immunosuppressive environment that hinders immune detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining Immunotherapy and Chemotherapy for Non-Small Cell Lung Cancer. Judd, J., Borghaei, H.[2020]

Cemiplimab is a PD-1 monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which is crucial for enhancing the immune response against cancer cells.

In September 2018, cemiplimab received FDA approval for treating patients with metastatic or locally advanced cutaneous squamous cell carcinoma who cannot undergo curative surgery or radiation, marking a significant advancement in cancer treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. Markham, A., Duggan, S.[2023]

Atezolizumab, cemiplimab, and pembrolizumab are established as standard first-line immunotherapy options for patients with advanced non-small cell lung cancer (NSCLC) who have high PD-L1 expression (≥50%).

The consensus among 25 Spanish lung cancer experts indicates that these therapies can be tailored to specific patient subgroups, enhancing treatment decision-making based on differences observed in pivotal clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Inhibitors as Monotherapy in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer Patients with High PD-L1 Expression: An Expert Position Statement. Isla, D., Sánchez, A., Casal, J., et al.[2023]

Cemiplimab-rwlc is a newly approved PD-1/L1 inhibitor for first-line treatment of metastatic non-small cell lung cancer (NSCLC) without EGFR or ALK mutations, either alone or with chemotherapy.

This review highlights the differences in patient populations studied for cemiplimab compared to other treatments, emphasizing its role in expanding options for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on Cemiplimab-rwlc in the Treatment of Non-Small Cell Lung Cancer (NSCLC): Focus on Patient Selection and Considerations. Ahn, J., Nagasaka, M.[2023]

In patients with advanced non-small-cell lung cancer (NSCLC) and high PD-L1 expression (≥50%), cemiplimab showed significant improvements in progression-free survival (PFS) and objective response rate (ORR) compared to pembrolizumab, based on a systematic review and network meta-analysis of randomized-controlled trials.

Cemiplimab demonstrated comparable overall survival (OS) and similar safety profiles to pembrolizumab, indicating it is a viable first-line treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50. Freemantle, N., Xu, Y., Wilson, FR., et al.[2022]

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

In a phase 3 study involving 710 patients with advanced non-small-cell lung cancer and high PD-L1 expression, cemiplimab significantly improved overall survival (not reached) and progression-free survival (8.2 months) compared to chemotherapy (14.2 months).

Cemiplimab also demonstrated a better safety profile, with fewer grade 3-4 treatment-emergent adverse events (28%) compared to chemotherapy (39%), making it a promising first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Sezer, A., Kilickap, S., Gümüş, M., et al.[2022]

The combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) has shown promising results in treating advanced Non-Small Cell Lung Cancer (NSCLC), indicating a potential new standard in immunotherapy.

Future studies are needed to further evaluate the safety, tolerability, and efficacy of this combination and other immunotherapeutic approaches, as the field is rapidly evolving with new treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The New Immunotherapy Combinations in the Treatment of Advanced Non-Small Cell Lung Cancer: Reality and Perspectives. Rocco, D., Gravara, LD., Gridelli, C.[2023]

Cemiplimab (Libtayo®) is the first approved immunotherapy for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who cannot undergo surgery or radiotherapy, showing a clinically significant objective response rate in the phase II EMPOWER-CSCC 1 trial.

The treatment has a durable effect, with the median duration of response and overall survival not yet reached, and it has an acceptable safety profile, with manageable immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. Lee, A., Duggan, S., Deeks, ED.[2020]

Citations

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igniting new hope for lung cancer - PMC - PubMed Central - NIH In this review, we will discuss the anti-PD-(L)1 resistance mechanism landscape in NSCLC and four novel modalities of immunotherapy in detail, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06162572

NCT06162572 | Phase 1b/2 Platform Study of Select ... This is a Phase 1b/2 study evaluating the anti-PD1 antibody, cemiplimab, in combination with either S095018 (anti-TIM3 antibody), S095024 (anti-CD73 ...

3. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-plus-chemotherapy-results-five-years

Libtayo® (cemiplimab) Plus Chemotherapy Results at Five ... Late-breaking data from exploratory analyses at WCLC show Libtayo plus chemotherapy demonstrates a more than double five-year overall ...

4. withpower.com withpower.com/trial/phase-2-non-small-cell-lung-cancer-nsclc-3-2024-50348

Immunotherapy Combinations for Lung Cancer Cemiplimab has been shown to be effective as a first-line treatment for advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression, as it helps the ...

5. clinicaltrials.servier.com clinicaltrials.servier.com/trial/NCT06162572/phase-1b2-platform-study-of-select-immunotherapy-combinations-in-participants-with-advanced-non-small-cell-lung-cancer-nsclc

Phase 1b/2 Platform Study of Select Immunotherapy ... S095018 blocks TIM3, S095024 blocks CD73, S095029 blocks NKG2A, and cemiplimab blocks PD-1. Research has shown that these combinations may help more patients ...

6. libtayohcp.com libtayohcp.com/nsclc/safety/combination-therapy/follow-up-data

Empower-lung 3: 2-year safety data Serious adverse reactions occurred in 48.7% of patients who received LIBTAYO plus chemotherapy, with the most common being anemia and neutropenia.

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