Study of cemiplimab with or without chemotherapy for non-small cell lung cancer patients with high PD-L1 levels to reduce rapid disease progression

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What is this study about?

This study involves patients with non-small cell lung cancer that has spread to other parts of the body. The cancer cells in this study show high levels of a protein called PD-L1, specifically 50% or more. The study will use a medication called cemiplimab, which is given under the brand name Libtayo, either by itself or in combination with chemotherapy drugs. The chemotherapy drugs that may be used include cisplatin, carboplatin, paclitaxel, and pemetrexed. These medications are given through a vein as an infusion. The purpose of this study is to compare how well cemiplimab combined with chemotherapy works compared to cemiplimab alone in reducing a condition called hyperprogression, which means the cancer grows very quickly after starting treatment, and early death.

During the study, patients will be divided into two groups. One group will receive cemiplimab alone, while the other group will receive cemiplimab together with chemotherapy. Before starting treatment, patients will have imaging scans performed to measure their cancer. These scans will be repeated at specific times during the study to see how the cancer is responding to treatment. Blood samples will also be collected to look at certain markers in the blood that might help doctors understand why some cancers grow quickly after treatment starts. The study looks specifically at a type of immune cell in the blood that may be connected to how the cancer responds to treatment.

The study will track several outcomes including how many patients experience rapid cancer growth, how many patients respond to treatment with their tumors shrinking, how long patients live without their cancer getting worse, and overall survival time. The study will also carefully monitor any side effects or unwanted reactions that patients may experience from the medications. Information gathered from imaging scans, blood tests, and tissue samples will help researchers better understand which patients might benefit most from receiving cemiplimab alone versus cemiplimab with chemotherapy.

1 Initial screening and baseline assessments

Blood samples will be collected to measure specific immune cells called CD10- LDNs (a type of white blood cell). The samples will be analyzed at a central laboratory.

Two CT scans (computed tomography scans, which are special x-ray images) will be reviewed. These scans must have been performed between 2 and 12 weeks apart before joining the trial. The scans will be sent to a central radiologist for confirmation that measurable disease is present.

A final baseline CT scan will be performed within 4 weeks before treatment starts. This scan will serve as the starting point for measuring how the disease responds to treatment.

2 Random assignment to treatment group

After completing all screening procedures, assignment to one of two treatment groups will occur randomly. One group will receive cemiplimab alone, and the other group will receive cemiplimab combined with chemotherapy.

The chemotherapy combination is abbreviated as PCT, which stands for platinum-based chemotherapy plus paclitaxel or pemetrexed. The specific chemotherapy drugs will depend on the type of lung cancer.

3 Treatment administration

All medications will be given through intravenous infusion, which means they will be delivered directly into a vein.

Cemiplimab is an immunotherapy drug that helps the immune system fight cancer cells. The dose is 350 mg and will be given as an infusion.

If assigned to the combination group, chemotherapy will also be administered. The platinum-based drugs include either cisplatin or carboplatin. These will be combined with either paclitaxel or pemetrexed, depending on the specific characteristics of the cancer.

The frequency and duration of treatment administration will follow standard protocols for these medications, with cycles typically repeated every few weeks.

4 First disease assessment scan

A CT scan will be performed approximately 5 weeks after starting treatment (within 5 days before or after the 5-week mark).

This scan will measure how the disease is responding to treatment by assessing the size and growth of tumors.

The scan results will be used to calculate the tumor growth rate, which helps determine if the disease is responding, staying stable, or progressing.

5 Second disease assessment scan

Another CT scan will be performed approximately 7 weeks after starting treatment (within 5 days before or after the 7-week mark).

This scan will provide additional information about how the disease is responding to treatment.

The results will be analyzed to determine if there is hyperprogression, which means the disease is growing faster than expected, or if treatment is working effectively.

6 Ongoing blood sample collection

Blood samples will be collected at various time points throughout the trial.

These samples will be used to analyze plasma (the liquid part of blood) and other blood components to understand how the body is responding to treatment.

The samples will help identify biological markers that may predict treatment response or side effects.

7 Safety monitoring

Throughout the trial, careful monitoring for adverse events (side effects or unwanted reactions) will occur.

Any side effects will be recorded and graded according to their severity using a standardized system called CTCAE version 5.0.

Special attention will be given to side effects that are related to the treatment medications.

8 Continued treatment and follow-up scans

Treatment will continue as long as the disease is not progressing and side effects remain manageable.

Additional CT scans will be performed at regular intervals to monitor disease status.

The scans will be evaluated using RECIST 1.1, which is a standard method for measuring tumor response to treatment.

9 Long-term follow-up

Follow-up will continue to track important outcomes such as progression-free survival (the length of time without disease worsening) and overall survival (the length of time alive).

Information about disease status and overall health will be collected at scheduled intervals.

The trial is expected to continue until December 2030, with follow-up assessments occurring throughout this period.

Who Can Join the Study?

You or your legal representative must provide written permission to take part in the study and agree to data protection rules
You must be 18 years old or older
Your general physical condition must be rated 0 to 2 on a scale called ECOG Performance Status, which measures how well you can perform daily activities
You must have a confirmed diagnosis of stage IV non-small cell lung cancer, which is an advanced form of lung cancer that has spread to other parts of the body
You must not have received any previous treatment for your advanced or returning lung cancer
A laboratory test must show that your cancer cells have a PD-L1 score of 50% or higher, which is a protein marker found on cancer cells
Your cancer must not have certain genetic changes called EGFR, ALK, or ROS1, which would require different treatments
A blood test must show that you have more than 30.5% of specific immune cells called CD10-negative low-density neutrophils in your blood
You must have at least one tumor that can be measured on imaging scans and has not been treated with radiation therapy before
You must have two CT scans (detailed imaging tests) performed before starting the study, taken between 2 and 12 weeks apart
A chest scan is required, and scans of both chest and abdomen are preferred
You must be able to have a baseline scan within 4 weeks before treatment begins
You must be willing to have blood samples taken for research purposes during the study
Your blood cell counts must meet minimum requirements: white blood cells above 1.5 x 10⁹ per liter, platelets at least 100 x 10⁹ per liter, and hemoglobin (oxygen-carrying protein in blood) at least 9.0 grams per deciliter
Your kidney function must be adequate, with a clearance rate of at least 60 milliliters per minute if receiving cisplatin chemotherapy, or at least 45 milliliters per minute if receiving carboplatin chemotherapy
Your liver function tests must show bilirubin (a substance processed by the liver) no higher than 1.5 times the normal upper limit, unless you have a harmless condition called Gilbert’s syndrome
Your liver enzyme levels (AST and ALT) must be no higher than 2.5 times the normal upper limit
You must not have had a severe allergic reaction (grade 3 or higher) to any of the chemotherapy drugs, cemiplimab (the immunotherapy drug being studied), or any of their ingredients

Who Cannot Join the Study?

The study information provided does not include specific reasons why patients cannot participate in this clinical trial
If you are considering joining this study, the research team will need to review your complete medical history to determine if you meet all requirements
General factors that often prevent participation in cancer clinical trials may include having other serious medical conditions, being pregnant or breastfeeding, or taking certain medications that could interfere with the study treatment
The study focuses on non-small cell lung cancer, which is a type of lung cancer that grows more slowly than other lung cancer types
The research team will evaluate whether the study medications, including cemiplimab (a type of immunotherapy drug that helps your immune system fight cancer), are safe and appropriate for your specific situation

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy
IRCCS Humanitas Research Hospital	Rozzano	Italy

Other Sites

Site Name	City	Country
Istituto Oncologico Veneto	Padua	Italy
Azienda Socio Sanitaria Territoriale Di Cremona	Cremona	Italy
ASST Fatebenefratelli Sacco	Milan	Italy
Azienda Unita Sanitaria Locale Di Piacenza	Piacenza	Italy
Fondazione IRCCS San Gerardo Dei Tintori	Monza	Italy
Asst Di Mantova	Mantova	Italy
Azienda Socio Sanitaria Territoriale Di Bergamo Ovest	Treviglio	Italy
Ospedale San Raffaele S.r.l.	Milan	Italy
ASST Grande Ospedale Metropolitano Niguarda	Milan	Italy
Fondazione IRCCS Policlinico San Matteo	Pavia	Italy
Universita’ Degli Studi Di Verona	Verona	Italy
IRCCS Ospedale Policlinico San Martino	Genoa	Italy
Cliniche Gavazzeni S.p.A.	Bergamo	Italy
Ospedale P. Pederzoli Casa Di Cura Privata S.p.A.	Peschiera Del Garda	Italy
Azienda Unita Sanitaria Locale Della Romagna	Faenza	Italy
Universita Degli Studi Di Brescia	Brescia	Italy
Fondazione I.R.C.C.S. Istituto Neurologico Besta	Milan	Italy
ASST Ospedale Maggiore di Crema	Crema	Italy
Anifmrw Ounucddauer Uefqqkgxljntw Pifle	Parma	Italy
Ipcwl Ibxdomfr Fgpaepzqssprn Oewlvfjpcssg Ipwzgxzx Nnkqsbill tgqcrq Rgawjz Esoyx	Rome	Italy
Iqtujdmt Rnpzcvjbx Ppj Lh Skvnik Dpu Tvlwok Dcdg Ajhryzo Ians Seftes	Meldola	Italy
Ayroxnm Uvhhw Sdvpkqhag Luqrdu Dz Baikrpz	Bologna	Italy
Auxiksp Oalaplqkilq Paxv Gcnpahya Xndnd	Bergamo	Italy
Uwvmdwnsrb Daldh Sxogz Ds Rpkm Lk Shauqegm	Rome	Italy

Trial status

Country	Status	Recruitment Start
Italy	Not yet recruiting	12.01.2026

Trial locations

Investigated drugs:

Cemiplimab is a type of immunotherapy medication that helps your immune system fight cancer. It works by blocking a protein called PD-1, which allows your body’s natural defenses to recognize and attack cancer cells more effectively. This medication is given through an infusion into your vein.

Platinum-based chemotherapy is a standard cancer treatment that uses powerful drugs to kill or slow the growth of cancer cells. In this trial, it may be combined with cemiplimab to see if the combination works better than cemiplimab alone in preventing rapid cancer growth in patients with non-small cell lung cancer.

Investigated diseases:

Non-small cell lung cancer

Non-Small Cell Lung Cancer – Non-small cell lung cancer is a type of cancer that begins in the lungs and is the most common form of lung cancer. The disease occurs when cells in the lung tissue start growing abnormally and uncontrollably, forming tumors. As the cancer progresses, these abnormal cells can spread to nearby tissues and other parts of the body through the bloodstream or lymphatic system. The disease can develop slowly over time, and its progression varies from person to person. In some cases, the cancer may grow and spread rapidly, while in others it may progress more slowly. The progression of the disease is typically monitored through imaging scans that measure tumor growth rate.

Trial ID:

2025-521583-35-00

Protocol code:

Hyperbolic

Trial Phase:

Therapeutic exploratory (Phase II)

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Study of cemiplimab with or without chemotherapy for non-small cell lung cancer patients with high PD-L1 levels to reduce rapid disease progression

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?