M1774 + Cemiplimab for Advanced Lung Cancer

Not currently recruiting at 72 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new drug combination, M1774 (an experimental treatment) and Cemiplimab (an immunotherapy drug), for individuals with advanced lung cancer unresponsive to previous treatments. Researchers seek to understand the safety, effectiveness, and pharmacokinetics of these drugs. Those with non-squamous non-small cell lung cancer that has progressed after certain therapies may find this study suitable. Participants must have measurable cancer and have experienced disease progression following treatments like anti-PD-(L)1 and platinum-based therapies. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants 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. It's best to discuss this with the trial team or your doctor.

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

Research has shown that the ATR inhibitor tuvusertib, when used alone, is generally well tolerated, meaning most people can handle it without serious problems. Cemiplimab has undergone extensive study and received FDA approval for certain types of cancer. It significantly improves survival rates for people with advanced lung cancer. While cemiplimab is usually safe, like most medications, it can cause side effects, typically mild to moderate.

In summary, previous studies have shown that both tuvusertib and cemiplimab are safe. This suggests that the combination being tested in the current trial might also be well tolerated. However, since this is an early-phase trial, more information is needed to fully understand the safety of using these two treatments together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about M1774 combined with Cemiplimab because this combination offers a fresh approach to tackling advanced lung cancer. Unlike standard treatments that often focus on chemotherapy and radiation, M1774 is designed to work alongside Cemiplimab, an immune checkpoint inhibitor, to enhance the body's immune response against cancer cells. This duo aims to provide a more targeted attack on cancer cells by boosting the immune system's ability to recognize and destroy them more effectively. The potential for this combination to improve outcomes with a new mechanism of action makes it a promising option in the fight against advanced lung cancer.

What evidence suggests that this trial's treatments could be effective for advanced lung cancer?

This trial investigates how combining M1774 and cemiplimab might treat advanced lung cancer. In previous studies, cemiplimab with chemotherapy more than doubled the five-year survival rate for some patients. M1774, also known as tuvusertib, blocks a protein called ATR, which aids cancer cells in repairing damaged DNA. This action could weaken cancer cells, making them easier to destroy. Early studies have shown M1774 to be well-tolerated, suggesting it could safely enhance treatment options. Overall, this combination aims to improve current treatments, particularly for patients whose cancer has continued to grow despite previous treatments. Participants in this trial will receive one of the dosing regimens of M1774 and cemiplimab being tested. ^{2 3 4 6 7}

Who Is on the Research Team?

Medical Responsible

Principal Investigator

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

Are You a Good Fit for This Trial?

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.

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05882734

Study Details | NCT05882734 | Tuvusertib (M1774) in ... This is an Open-label, multicenter clinical study conducted in two Phases to establish the efficacy, safety, tolerability, and pharmacokinetics of the ...

2. 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 ...

3. jto.org jto.org/article/S1556-0864(24)02291-3/fulltext

EP.12H.09 Phase 1b/2a Study of ATR Inhibitor Tuvusertib ... This open-label, multicentre, Phase 1b/2a study (NCT05882734) evaluates the efficacy, safety, tolerability, and pharmacokinetics of tuvusertib + cemiplimab.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11094421/

First-in-Human Study of the Ataxia Telangiectasia and Rad3 ... This first-in-human study demonstrates that ataxia telangiectasia and Rad3-related inhibitor tuvusertib as monotherapy is well tolerated, has a manageable ...

5. esmoopen.com esmoopen.com/article/S2059-7029(24)00451-4/fulltext

104TiP Phase Ib/IIa study of ATR inhibitor tuvusertib + anti- ... This open-label, multicentre, phase Ib/IIa study (NCT05882734) evaluates the efficacy, safety, tolerability, and pharmacokinetics of tuvusertib + cemiplimab.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05882734

Study Details | NCT05882734 | Tuvusertib (M1774) in ... This is an Open-label, multicenter clinical study conducted in two Phases to establish the efficacy, safety, tolerability, and pharmacokinetics of the ...

7. withpower.com withpower.com/trial/phase-2-lung-neoplasms-6-2023-f0f00

M1774 + Cemiplimab for Advanced Lung Cancer What data supports the effectiveness of the drug Cemiplimab in treating advanced lung cancer? Cemiplimab has shown significant improvement in overall survival ...