Immunotherapy Combinations for Lung Cancer

Recruiting at 77 trial locations

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

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Servier Bio-Innovation LLC

Must not be taking: Steroids, Antibiotics, others

Disqualifiers: Brain metastases, Autoimmune disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a Phase 1b/2 study evaluating the anti-PD1 antibody, cemiplimab, in combination with either S095018 (anti-TIM3 antibody), S095024 (anti-CD73 antibody), or S095029 (anti-NKG2A antibody) in adult participants with previously untreated advanced/metastatic non-small cell lung cancer (NSCLC) with high PD-L1 expression. The study includes two parts: part A, the combination-therapy safety lead-in phase to determine the recommended dose for expansion (RDE) for S095018, S095024, and S095029 in combination with cemiplimab and part B, the randomized dose expansion phase to assess the efficacy of S095018, S095024, or S095029 in combination with cemiplimab. Study treatment will be administered for a maximum of 108 weeks, or until confirmed disease progression per iRECIST and/ or until meeting other treatment discontinuation criteria.

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.

What data supports the effectiveness of the drug cemiplimab 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 immune system attack cancer cells. It is also approved for treating advanced cutaneous squamous cell carcinoma, indicating its potential in treating other cancers. ^{1 2 3 4 5}

Is cemiplimab safe for use in humans?

Cemiplimab has been shown to have an acceptable safety profile in clinical trials for advanced cutaneous squamous cell carcinoma and non-small cell lung cancer, with most side effects being manageable with appropriate treatment or discontinuation of the drug. ^{1 2 4 6 7}

How is the drug Cemiplimab different from other treatments for lung cancer?

Cemiplimab is unique because it is a PD-1 inhibitor that can be used as a first-line treatment for advanced non-small cell lung cancer, either alone or in combination with chemotherapy, particularly for tumors with high PD-L1 expression. This drug works by blocking a pathway that tumors use to hide from the immune system, thereby enhancing the body's ability to fight cancer. ^{1 2 3 8 9}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Cemiplimab (Monoclonal Antibodies)
• S095018 (Monoclonal Antibodies)
• S095024 (Monoclonal Antibodies)
• S095029 (Monoclonal Antibodies)

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.

Participant Groups

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 Canada, Brazil for the following indications:

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+

Findings from Research

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]

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 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]

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 (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]

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]

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]

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]

References

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

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. [2019]

2. New Zealand 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. [2023]

3. England 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. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Cemiplimab: First Global Approval. [2023]

5. Switzerland 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. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. [2020]

7. England 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. [2022]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The New Immunotherapy Combinations in the Treatment of Advanced Non-Small Cell Lung Cancer: Reality and Perspectives. [2023]

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

Combining Immunotherapy and Chemotherapy for Non-Small Cell Lung Cancer. [2020]