M1774 + Cemiplimab for Advanced Lung Cancer

Recruiting at 53 trial locations

Overseen By Communication Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: EMD Serono Research & Development Institute, Inc.

Disqualifiers: EGFR, ALK aberrations, Brain metastases, others

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

Compensation: Varies

Number of Visits: Unknown

61 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an Open-label, multicenter clinical study conducted in two Phases to establish the efficacy, safety, tolerability, and pharmacokinetics of the ataxia telangiectasia mutated and Rad3-related protein kinase (ATR) inhibitor Tuvusertib in Combination with Cemiplimab in Participants with Non-Squamous Non-Small Cell Lung Cancer (nsqNSCLC) that has Progressed on Prior Anti-PD-(L)1 and Platinum-based Therapies..

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug Cemiplimab in treating advanced lung cancer?

Cemiplimab has shown significant improvement in overall survival and progression-free survival compared to chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with high PD-L1 expression (≥50%). ^{1 2 3 4 5}

What safety data exists for Cemiplimab in humans?

Cemiplimab has been studied for safety in treating advanced non-small cell lung cancer (NSCLC) and cutaneous squamous cell carcinoma (CSCC). Common side effects include immune system-related reactions, but it is generally considered safe for use in these conditions. ^{2 3 4 6 7}

What makes the drug M1774 + Cemiplimab unique for advanced lung cancer?

The combination of M1774 and Cemiplimab is unique because Cemiplimab is a PD-1 inhibitor, which helps the immune system recognize and attack cancer cells, and it is one of the few options available for patients with high PD-L1 expression in non-small cell lung cancer (NSCLC). This combination may offer a novel approach by potentially enhancing the immune response against cancer cells compared to using Cemiplimab alone. ^{2 3 8 9 10}

Research Team

Medical Responsible

Principal Investigator

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Eligibility Criteria

This trial is for adults with non-squamous Non-Small Cell Lung Cancer (nsqNSCLC) that worsened after anti-PD-(L)1 and platinum-based treatments. They must have shown some positive response to previous therapies, have measurable disease, be in good physical condition (ECOG PS 0 or 1), and have proper organ function. People with certain lung conditions, other cancers within the last three years, brain metastases, or specific genetic mutations are not eligible.

Inclusion Criteria

My tumor's genetic changes were analyzed using a certified liquid biopsy test.

Other protocol defined inclusion criteria could apply

My previous treatment with anti-PD-(L)1 therapy showed stable disease or improvement.

Exclusion Criteria

I have had pneumonitis treated with steroids or currently have lung disease.

I have had another type of cancer within the last 3 years.

My cancer has specific changes in the EGFR or ALK genes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Participants receive M1774 in combination with Cemiplimab to evaluate safety, tolerability, and pharmacokinetics

8-12 weeks

Phase 2a Treatment

Participants receive either Dosing Regimen 1 or 2 as finalized in Phase 1b to evaluate efficacy

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cemiplimab
• M1774

Trial Overview The study tests M1774 combined with Cemiplimab on patients whose nsqNSCLC has progressed despite prior treatments. It's an open-label trial meaning everyone knows what treatment they're getting. The goal is to see how well this combo works in terms of safety and effectiveness while also studying how the body processes these drugs.

Participant Groups

Group I: Stratum C (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b Experimental Treatment 2 Interventions

Group II: Stratum B (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b Experimental Treatment 2 Interventions

Group III: Stratum A (Phase 2a): Either Dosing Regimen 1 or 2 as finalized in Phase 1b Experimental Treatment 2 Interventions

Group IV: Dosing Regimen 2 (Phase 1b): M1774 + Cemiplimab Experimental Treatment 2 Interventions

Group V: Dosing Regimen 1 (Phase 1b): M1774 + Cemiplimab Experimental Treatment 2 Interventions

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?

EMD Serono Research & Development Institute, Inc.

Lead Sponsor

Trials

86

Recruited

22,700+

Miguel Fernández Alcalde

EMD Serono Research & Development Institute, Inc.

Chief Executive Officer

Bachelor’s Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master’s Degree in Management from IESE Business School

Danny Bar-Zohar

EMD Serono Research & Development Institute, Inc.

Chief Medical Officer since 2022

MD

Merck KGaA, Darmstadt, Germany

Industry Sponsor

Trials

449

Recruited

122,000+

Danny Bar-Zohar

Merck KGaA, Darmstadt, Germany

Chief Medical Officer since 2022

MD

Belén Garijo

Merck KGaA, Darmstadt, Germany

Chief Executive Officer since 2021

MD

Findings from Research

Platinum-based chemotherapy remains the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) without identifiable genetic mutations, but immune checkpoint inhibitors like pembrolizumab and nivolumab are changing the treatment landscape by significantly improving survival rates with manageable safety profiles.

Pembrolizumab is specifically approved for PD-L1-positive NSCLC, while nivolumab and atezolizumab can be used regardless of PD-L1 expression, highlighting the need for ongoing research into additional biomarkers to better identify patients who will benefit from these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of nivolumab, pembrolizumab, and atezolizumab in treatment of advanced non-small cell lung cancer. Chen, R., Tao, Y., Xu, X., 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]

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]

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]

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-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]

Mobocertinib (TAK-788) is specifically designed to target exon 20 insertion mutations of EGFR in non-small cell lung cancer (NSCLC) and has shown a 28% objective response rate in a phase I/II trial involving platinum-pretreated patients.

The treatment demonstrated a median progression-free survival of 7.3 months and a duration of response of 17.5 months, leading to its accelerated approval by the FDA in 2021 as the first TKI for this specific mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mobocertinib in non-small cell lung cancer. Liu, S., Lowder, KE.[2022]

References

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

The efficacy and safety of nivolumab, pembrolizumab, and atezolizumab in treatment of advanced non-small cell lung cancer. [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. 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]

4. 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]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Receptor kinase inhibitors target NSCLC: two antibodies and a small-molecule MET inhibitor. [2023]

8. Spain pubmed.ncbi.nlm.nih.gov

Mobocertinib in non-small cell lung cancer. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Real-world efficacy and safety of mobocertinib in EGFR exon 20 insertion-mutated lung cancer. [2022]

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

Spotlight on Mobocertinib (TAK-788) in NSCLC with EGFR Exon 20 Insertion Mutations. [2021]