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Morning Versus Afternoon Pembrolizumab, Carboplatin, and Pemetrexed in Adults With Stage IV Non-Squamous Non-Small Cell Lung Cancer

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is studying stage IV non-squamous non-small cell lung cancer, a type of advanced lung cancer that has spread beyond the lung. The treatment used in the study is a combination of pembrolizumab, carboplatin, and pemetrexed, all given through a vein. The purpose of the study is to see whether the time of day when pembrolizumab is started, in the morning or in the afternoon, affects survival after one year.

People in the study receive the same cancer treatment, but pembrolizumab is started at different times of day. One group receives it in the morning, between 08:00 and 12:00, and the other group receives it in the afternoon, between 13:00 and 17:00. Treatment is then continued over several cycles, with regular medical checks during the study. The study looks at survival, cancer growth, side effects, and how treatment affects daily well-being and sleep.

The study is a randomized phase III trial, which means the treatment timing is assigned by chance and the treatment plan is being tested in a larger group of patients. The study is designed for adults with advanced lung cancer and will follow results over time to compare the two timing schedules.

The research process

The trial runs in 7 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Randomisation and treatment schedule

    After joining the study, you are assigned to one of two treatment time groups. In one group, pembrolizumab is started in the morning, between 08:00 and 12:00. In the other group, pembrolizumab is started in the afternoon, between 13:00 and 17:00.

    The study compares the effect of the time of pembrolizumab infusion on the 1-year survival rate.

  2. Step 2

    Treatment administration

    You receive pembrolizumab by intravenous infusion at a dose of 250 mg.

    You also receive carboplatin by intravenous infusion at a dose of 750 mg.

    You also receive pemetrexed by intravenous infusion at a dose of 500 mg/m², which means the dose is based on your body surface area.

    These medicines are given as part of the first treatment line for metastatic non-squamous lung cancer. The trial compares the timing of pembrolizumab administration, not the use of the medicines themselves.

  3. Step 3

    First evaluation

    Your first treatment response assessment is usually done at about 6 weeks.

    This assessment uses scans such as TAP scan (a scan of the chest, abdomen, and pelvis), brain scan, pet scan (a scan that shows how active tissues are), and/or mri (magnetic resonance imaging, a detailed scan using magnets).

    The purpose of this evaluation is to check the early response of the tumour to treatment.

  4. Step 4

    Repeat assessments during the first year

    During the first year, tumour response is checked again using TAP scan, brain scan, pet scan, and/or mri as needed.

    The study measures the best tumour response over 1 year and also records how long it takes before treatment stops for any reason.

  5. Step 5

    Questionnaires and self-assessments

    At the start of the study, you complete questionnaires about your quality of life and sleep.

    You repeat the quality of life questionnaires every 4 treatment courses up to 1 year, at C4, C8, C12, and C16.

    You repeat the sleep questionnaire every 4 treatment courses up to 1 year, at C4, C8, C12, and C16.

    You complete the chronotype questionnaire, which measures whether you tend to be more active in the morning or evening, at the start of the study, and again at C4 and C8.

  6. Step 6

    Safety monitoring

    During the trial, any side effects are recorded and grouped by how severe they are, from grade 1 to grade 5.

    The study follows your treatment until it stops, whether because of cancer growth, side effects, loss of follow-up, refusal, the end of the protocol, or death.

  7. Step 7

    End of study follow-up

    The main study outcome is the 1-year survival rate, which means the chance of being alive 1 year after randomisation.

    Other outcomes measured during the study include the time until cancer gets worse, overall survival, treatment response, side effects, quality of life, sleep, and the timing of treatment discontinuation.

Who can join the trial?

17 criteria

  • The patient must have a confirmed diagnosis of stage IV non-squamous non-small cell lung cancer (NSCLC). Confirmed means the diagnosis was proven by a tissue test (histology) or a cell test (cytology).
  • The cancer must be non-squamous, meaning it is not the squamous cell type of lung cancer.
  • The cancer must be advanced/metastatic, meaning it has spread beyond the original place in the lung.
  • The patient must have measurable disease according to RECIST 1.1, which means the tumors are large enough to be measured on scans.
  • The patient must not have received prior systemic treatment for advanced or metastatic NSCLC. Systemic treatment means treatment that travels through the whole body, such as chemotherapy or similar medicines.
  • Patients who had adjuvant or neoadjuvant treatment may still qualify if that treatment ended at least 12 months before the metastatic disease appeared. Adjuvant treatment is given after the main treatment, and neoadjuvant treatment is given before the main treatment.
  • The patient must provide tumor tissue for testing. If possible, the tissue should come from a place that was not treated with radiation before the biopsy. A biopsy is a small sample of tissue taken for testing.
  • The patient must have testing showing that EGFR-directed or ALK-directed therapy is not needed, meaning there are no activating EGFR mutations and no ALK gene rearrangements. A mutation is a change in a gene, and a gene rearrangement is when a gene is broken and joined in a different way.
  • Instead of the above gene findings, the patient may qualify if there is a K-Ras mutation.
  • The patient must be 18 years of age or older on the day they sign the consent form.
  • The patient must have a life expectancy of at least 3 months, meaning the doctor expects they are likely to live for at least that long.
  • The patient must have an ECOG performance status of 0 or 1. This is a measure of how well a person can do daily activities. 0 means fully active, and 1 means they are restricted in physically strenuous activity but can still do light work.
  • The patient must have adequate organ function, including blood counts, liver function, and kidney function. Adequate means the organs are working well enough for study treatment.
  • The patient must agree to take part by signing written informed consent, which means they understand the study and voluntarily agree to join.
  • The patient must have affiliation with the French social security system.
  • If the patient is a woman who can become pregnant, she must agree to use effective contraception during the study and for 120 days after the last dose of study medicine, or for 180 days after the last dose of chemotherapy if that applies. Contraception means methods used to prevent pregnancy.
  • If the patient is a man with a female partner who can become pregnant, he must agree to use effective contraception during the study.

Who cannot join the trial?

31 criteria

  • Having predominantly squamous cell non-small cell lung cancer, meaning the tumor is mostly made of a different cell type than the one allowed in this study.
  • Having active central nervous system (CNS) metastases, meaning the cancer has spread to the brain or spinal cord and is currently active.
  • Having carcinomatous meningitis, meaning cancer cells are in the fluid or membranes around the brain and spinal cord.
  • Having had a severe allergic reaction to another monoclonal antibody (mAb), a type of laboratory-made medicine that acts like an antibody.
  • Having a known sensitivity or allergy to any part of carboplatin or pemetrexed, which are study medicines.
  • Having a medical reason that makes the study medicines or related medicines unsafe to use.
  • Having active autoimmune disease that needed treatment in the past 2 years, meaning the immune system attacks the body and required medicines such as steroids or drugs that calm the immune system.
  • Using chronic systemic steroids, meaning steroid medicine taken regularly by mouth or injection throughout the body. People using only occasional inhalers, inhaled steroids, or local steroid injections for asthma would not be excluded for this reason.
  • Being unable to stop aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), which are common pain and inflammation medicines, for the required time before treatment.
  • Being unwilling or unable to take folic acid or vitamin B12 supplements.
  • Having had previous treatment with another anti-PD-1, PD-L1, or PD-L2 medicine, or another medicine that targets immune control pathways.
  • Having an active infection that needs treatment.
  • Currently taking part in another study and receiving study treatment, or having used an investigational medicine or device within 4 weeks before pembrolizumab starts. Investigational means not yet approved for general use.
  • Having a known history of HIV infection, meaning positive tests for human immunodeficiency virus.
  • Having known active hepatitis B or hepatitis C, which are viral infections that affect the liver.
  • Having any medical condition, treatment, or lab result that could make the study results unclear, make it hard to finish the study, or be unsafe to join, if the doctor thinks so.
  • Having a psychiatric condition or substance abuse problem that would make it hard to follow the study rules.
  • Having interstitial lung disease, a lung condition that causes scarring, or a past lung inflammation called pneumonitis that needed steroid treatment by mouth or vein.
  • Being pregnant, breastfeeding, or planning to become pregnant or father a child during the study period.
  • Being under AME, a legal protection measure.
  • Being an adult under legal protection such as guardianship, curatorship, or safeguard of justice, which are legal arrangements for protected adults.
  • Being deprived of liberty by a court or administrative decision, meaning being in custody or otherwise not free to participate.
  • Having already received systemic cytotoxic chemotherapy for metastatic disease before the first study dose. This means prior whole-body cancer drug treatment for cancer that has spread.
  • Having already received antineoplastic biological therapy before the first study dose, such as erlotinib, crizotinib, or cetuximab. These are cancer-targeting medicines.
  • Having had major surgery within 6 months before the first study dose.
  • Having received radiation therapy to the lung of more than 30 Gy within 6 months before the first study dose. Gy means Gray, a unit used to measure radiation dose.
  • Having completed palliative radiotherapy within 7 days before the first study dose. Palliative radiotherapy is radiation used to ease symptoms rather than to cure the cancer.
  • Being expected to need any other anticancer treatment while in the study.
  • Having received a live-virus vaccine within 30 days before the planned start of treatment.
  • Having diverticulitis that is active, meaning inflamed small pouches in the bowel; having an intra-abdominal abscess, meaning a pocket of infection in the abdomen; having a bowel obstruction, meaning the intestines are blocked; or having abdominal carcinomatosis, meaning cancer spread throughout the abdomen.
  • Having had a previous cancer, unless it was treated with the goal of cure and there has been no sign of that cancer coming back for at least 5 years.
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Investigated drugs

  • Pemetrexed

    is a cancer medicine given through a vein. In this trial, it is used as part of the first treatment for metastatic non-squamous lung cancer. It helps stop cancer cells from growing and dividing.

  • Keytruda

    is an immunotherapy medicine given through a vein. It helps the body’s immune system recognize and attack cancer cells. In this study, it is being tested to see whether giving it in the morning or in the afternoon changes how well it works.

  • Carboplatin

    is a chemotherapy medicine given through a vein. It is used to kill cancer cells or slow their growth. In this trial, it is combined with the other study medicines as part of the first-line treatment.

What is already known about the treatment

  • Pemetrexed

    Pemetrexed is given as an intravenous infusion, meaning it is delivered directly into a vein by a healthcare professional. It is a well-established cancer medicine in medical practice and is widely described in the medical literature for treating certain types of lung cancer and other cancers. It is classified as an antifolate antimetabolite, and it works by blocking enzymes that cancer cells need to make DNA and grow, which helps slow or stop tumor cell division.

  • Pembrolizumab

    Pembrolizumab is given as an intravenous infusion, usually through a vein in a hospital or clinic. It is a widely used and well-studied cancer medicine in current medical practice, especially in modern immunotherapy. It is a monoclonal antibody and an immune checkpoint inhibitor used for cancers such as non-small cell lung cancer, melanoma, and several others; it works by blocking the PD-1 protein on immune cells, which helps the body’s own immune system recognize and attack cancer cells more effectively.

  • Carboplatin

    Carboplatin is given as an intravenous infusion, meaning it is administered directly into a vein by medical staff. It is an established chemotherapy medicine with a long history of use in medicine and is well described in the medical literature. It belongs to the platinum-based anticancer drugs and is used for many cancers, including lung cancer; it works by damaging the cancer cell’s DNA, which makes it harder for the cells to grow and divide.

Investigated diseases

Stage IV non-squamous non-small cell lung cancer - This is an advanced form of lung cancer that starts in the lung tissue and is not made of squamous cells. It is called stage IV when it has spread beyond the lung to other parts of the body. The disease usually grows over time and may cause new tumors to appear in other organs. Its course often includes periods of tumor growth, spread, and changes in symptoms as the cancer advances.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2025-521891-78-00Protocol codeAPHP241011Estimated enrolment254 patientsSponsorAssistance Publique Hopitaux De Paris

sourced from the EU Clinical Trials Register and site verification

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