Maintenance Pembrolizumab at Usual or Low doSE in Non-squamous Lung Cancer: a Non-inferiority Study

NCT ID: NCT05692999

Last Updated: 2025-06-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1166 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-20

Study Completion Date

2029-01-31

Brief Summary

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Pulse is a randomized non-inferiority phase III clinical trial assessing a new mode of immunotherapy administration based on increased interval time between 2 infusions as maintenance treatment in Pulse arm compared with the conventional administration in Control arm.

In both treatment arms, pembrolizumab alone or combined with pemetrexed is allowed as maintenance treatment. Indeed :

In Pulse arm : Pembrolizumab 200 mg will be administered to patients every 6 weeks (Q6W) plus, in the absence of contra-indication pemetrexed 500 mg/m\^2 will be administered every 3 weeks (Q3W).

In control arm : Pembrolizumab 200 mg will be administered to patients every 3 weeks (Q3W) or 400 mg every 6 weeks plus,in the absence of contra-indication pemetrexed 500 mg/m\^2 will be administered every 3 weeks (Q3W).

Detailed Description

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Conditions

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Metastatic Non-squamous Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pulse Arm

Group Type EXPERIMENTAL

Pembrolizumab 200 mg Q6W

Intervention Type DRUG

Pembrolizumab 200mg Q6W

Pemetrexed 500 mg/m^2 Q3W

Intervention Type DRUG

Pemetrexed 500 mg/m\^2 Q3W

Control Arm

Group Type ACTIVE_COMPARATOR

Pemetrexed 500 mg/m^2 Q3W

Intervention Type DRUG

Pemetrexed 500 mg/m\^2 Q3W

Pembrolizumab 200 mg Q3W or 400 mg Q6W

Intervention Type DRUG

Pembrolizumab 200 mg Q3W or 400 mg Q6W

Interventions

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Pembrolizumab 200 mg Q6W

Pembrolizumab 200mg Q6W

Intervention Type DRUG

Pemetrexed 500 mg/m^2 Q3W

Pemetrexed 500 mg/m\^2 Q3W

Intervention Type DRUG

Pembrolizumab 200 mg Q3W or 400 mg Q6W

Pembrolizumab 200 mg Q3W or 400 mg Q6W

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

A) To be checked before the induction phase (only for patient included before induction phase) :

1. Histologically or cytologically confirmed diagnosis of non-squamous non-small cell lung cancer (NSCLC).
2. Non-operable / non-irradiable stage III or stage IV.
3. Patient must be eligible to receive 3 or 4 cycles of induction treatment combination with pembrolizumab plus platinum (cisplatin or carboplatin) and pemetrexed.
4. In the presence of an EGFR mutation, an ALK or ROS1 rearrangement the patient must have received at least one specific targeted therapy line.
5. Age ≥ 18 years old.
6. Performance status 0 or 1.
7. Signed informed consent.
8. Patient affiliated to a social security system or beneficiary of the same.

B) To be checked before the maintenance phase (for all patient) :

1. Histologically or cytologically confirmed diagnosis of non-squamous non-small cell lung cancer (NSCLC).
2. Non-operable / non-irradiable stage III or stage IV.
3. Received 3 or 4 cycles of induction treatment combination with pembrolizumab plus platinum (cisplatin or carboplatin) and pemetrexed.
4. Patient must be eligible to receive maintenance pembrolizumab with or without pemetrexed, last induction chemotherapy cycle within 42 days before randomization.
5. Stable disease, partial or complete response according to RECIST 1.1 criteria after induction chemotherapy and pembrolizumab. Targets lesions are not required before randomization.
6. In the presence of an EGFR mutation, an ALK or ROS1 rearrangement the patient must have received at least one specific targeted therapy line (not needed a second time if already checked before induction phase).
7. Patients with baseline brain metastases will be eligible in case of stability or no evidence of progression and if they remain clinically stable.
8. Age ≥ 18 years old.
9. Performance status 0 or 1.
10. Signed informed consent (only for patient included after induction phase).
11. Patient affiliated to a social security system or beneficiary of the same.
12. Creatinine clearance \> 30 ml/min by Cockcroft-Gault\* or MDRD in case that patient will start maintenance just with pembrolizumab but ≥ 45 ml/min if the patient will receive pemetrexed plus pembrolizumab.

\*Cockcroft- Gault Formula:
* Female CrCl = \[(140 - age in years) x weight in kg x 0.85\] / 72 x serum creatinine in mg/dL;
* Male CrCl = \[(140 - age in years) x weight in kg x 1.00\] /72 x serum creatinine in mg/dL.
13. Neutrophils ≥ 1500/μL and platelets ≥ 100 000/μL.
14. Bilirubin ≤ 1.5 upper limit normal (ULN).
15. Transaminases, Alkaline phosphatase ≤ 2.5 x the ULN except in case of liver metastases (5 x ULN).
16. Patients might have received platinum-based chemotherapy as an adjuvant or neoadjuvant treatment, or with radiotherapy for a localized lung cancer, provided that the chemotherapy was ended more than 6 months before the first cycle of induction chemotherapy.
17. Patients might have received previous immune checkpoint inhibitors as an adjuvant or neoadjuvant treatment, or as a consolidation treatment after radiotherapy for a localized lung cancer, but the immune checkpoint inhibitors must be finished at least than 12 months before the first cycle of induction chemotherapy for advanced stage.
18. A woman is eligible for the study if she is no longer likely to procreate (physiologically unfit to carry out a pregnancy), which includes women who have had: a hysterectomy, an oophorectomy, a bilateral tubal ligation.

Post-menopausal women:
* Patients not using hormone replacement therapy should have had a complete cessation of menstruation for at least one year and be over 40 years of age, or, if in doubt, have an FSH (Follicle Stimulating Hormone) level \> 40 mIU/mL and an estradiol level \< 40 pg/mL (\< 150 pmol/L).
* Patients using hormone replacement therapy must have had a complete cessation of menstruation for at least one year and be over 45 years of age or have evidence of menopause (FSH and estradiol levels) before starting hormone replacement therapy.
19. Women who are likely to procreate are eligible if they have a negative serum pregnancy test in the week before the first dose of treatment and preferably as close as possible to the first dose and if they agree to use an effective contraceptive method during the course of the study through 4 months after the last dose of study medication.

Sexually active males patients must agree to use condom during the study and for at least 4 months after the last study treatment administration. Also, it is recommended their women of childbearing potential partner use a highly effective method of contraception.

Exclusion Criteria

A) To be checked before the induction phase (only for patient included before induction phase) :

1. Mixed small-cell, squamous-cell carcinoma.
2. Mental or psychological illness that does not allow the patient to give informed consent.
3. Pregnant or breastfeeding women.
4. History of HIV or chronic hepatitis B or C.
5. Active or uncontrolled infection.
6. History of one or more of the following cardiovascular disorders in the previous 6 months:

* Coronary artery bypass or peripheral arterial bypass, cardiac angioplasty or stent.
* Myocardial infarction
* Severe or unstable angina pectoris
* Peripheral vascular disease, pulmonary embolism or untreated thromboembolic events, stroke or transient ischemic attack. Note: Patients with recent deep vein thrombosis (including pulmonary embolism) treated with anticoagulant for at least 4 weeks and clinically stable are eligible.
* Congestive heart failure class III or IV as defined by the NYHA
7. Concomitant treatment with another experimental treatment or participation in another clinical trial.

B) To be checked before the maintenance phase (for all patient) :

1. Presence of grade 3 or 4 toxicity related to pembrolizumab limiting maintenance treatment continuation.
2. Mixed small-cell, squamous-cell carcinoma.
3. Corticosteroids at a dose greater than 20 mg per day of prednisone or equivalent.
4. Patient unable to follow the therapeutic program.
5. Mental or psychological illness that does not allow the patient to give informed consent.
6. Pregnant or breastfeeding women.
7. Ongoing immunosuppressive systemic therapy (cyclophosphamide, aziatropin, methotrexate, thalidomide and anti-TNF).
8. Active autoimmune diseases. History of autoimmune diseases including myasthenia gravis, lupus erythematosus, rheumatoid arthritis, irritable bowel syndrome, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis or glomerulonephritis. Patients with a history of autoimmune hypothyroidism treated with a stable dose of hormone replacement therapy are eligible. Patients with diabetes treated with insulin are eligible.
9. History of idiopathic pulmonary fibrosis, organized pneumonia (i.e., obliterating bronchiolitis), drug-induced lung disease or active signs of pneumonia, pulmonary infiltration (regardless of cause) detected on the baseline chest CT-scan.
10. History of any other hematologic or primary solid tumor malignancy unless in remission for at least 2 years and without specific treatment (as example, not allowed hormonal therapy to replace for breast cancer or hormonal therapy substitution in prostate cancer). pT1-2 prostatic cancer Gleason score \< 6, superficial bladder cancer, non-melanoma skin cancer or carcinoma in situ of the cervix are allowed.
11. Presence of a condition or condition that makes patient participation in the study inappropriate, including serious unresolved or unstable toxicities from previous administration of another experimental treatment or any medical condition that could interfere with patient safety, obtaining consent or compliance with study procedures.
12. Administration of a live attenuated vaccine within the 4 weeks before day 1 of Cycle 1 or administration of a live attenuated vaccine planned for the duration of the study. The flu vaccine can be given during the flu season (approximately from October to May). Patients should not receive a live attenuated influenza vaccine during the 4 weeks preceding day 1 of Cycle 1 and should not receive this type of vaccine during the study.
13. History of HIV or chronic hepatitis B or C (not needed a second time if already checked before induction phase).
14. Active or uncontrolled infection.
15. History of one or more of the following cardiovascular disorders in the previous 6 months:

* Coronary artery bypass or peripheral arterial bypass, cardiac angioplasty or stent.
* Myocardial infarction
* Severe or unstable angina pectoris
* Peripheral vascular disease, pulmonary embolism or untreated thromboembolic events, stroke or transient ischemic attack. Note: Patients with recent deep vein thrombosis (including pulmonary embolism) treated with anticoagulant for at least 4 weeks and clinically stable are eligible.
* Congestive heart failure class III or IV as defined by the NYHA
16. Concomitant treatment with another experimental treatment or participation in another clinical trial.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Benjamin BESSE

Role: PRINCIPAL_INVESTIGATOR

Gustave Roussy, Cancer Campus, Grand Paris

Locations

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CHU UCL Namur - Site Sainte Elisabeth

Namur, , Belgium

Site Status RECRUITING

Centre Hospitalier de Carcassonne

Carcassonne, Aude, France

Site Status RECRUITING

Clinique Sainte Anne - Strasbourg

Strasbourg, Bas-Rhin, France

Site Status RECRUITING

Institut de Cancérologie Strasbourg Europe (ICANS)

Strasbourg, Bas-Rhin, France

Site Status RECRUITING

Hôpital Européen de Marseille

Marseille, Bouches-du-Rhône, France

Site Status RECRUITING

Groupe Hospitalier La Rochelle

La Rochelle, Charente-Maritime, France

Site Status RECRUITING

Centre Hospitalier Régional Universitaire de Brest (Hôpital Morvan)

Brest, Finistère, France

Site Status RECRUITING

Centre Hospitalier des Pays de Morlaix

Morlaix, Finistère, France

Site Status RECRUITING

Groupe Hospitalier de la Région de Mulhouse et Sud Alsace

Mulhouse, Haut-Rhin, France

Site Status RECRUITING

Centre Hospitalier de Bigorre

Tarbes, Hautes-Pyrénées, France

Site Status RECRUITING

Hôpital Foch

Suresnes, Hauts-de-Seine, France

Site Status RECRUITING

Centre Hospitalier de Béziers

Béziers, Hérault, France

Site Status RECRUITING

CHU Rennes

Rennes, Ille-et-Vilaine, France

Site Status RECRUITING

Centre Hospitalier de Saint-Malo

St-Malo, Ille-et-Vilaine, France

Site Status RECRUITING

Centre Hospitalier Régional Universitaire de Tours

Tours, Indre-et-Loire, France

Site Status RECRUITING

Centre Hospitalier Universitaire - La Réunion - Site Felix Guyon

Saint-Denis, La Réunion, France

Site Status NOT_YET_RECRUITING

Centre Hospitalier Universitaire - La Réunion - Site Sud

Saint-Pierre, La Réunion, France

Site Status NOT_YET_RECRUITING

Centre Hospitalier Régional d'Orléans - NHO

Orléans, Loiret, France

Site Status RECRUITING

Hospices Civils de Lyon - Hôpital Louis Pradel

Bron, Lyon, France

Site Status RECRUITING

Centre Hospitalier de Cholet

Cholet, Maine-et-Loire, France

Site Status RECRUITING

Centre Hospitalier Intercommunal de Compiègne-Noyon

Compiègne, Oise, France

Site Status RECRUITING

CHU St-Etienne

Saint Priest En Jarez, Pays de la Loire Region, France

Site Status RECRUITING

Centre Hospitalier de la Côte Basque

Bayonne, Pyrénées-Atlantiques, France

Site Status RECRUITING

Centre Hospitalier Intercommunal Créteil

Créteil, Val-de-Marne, France

Site Status RECRUITING

Hôpital d'Instruction des Armées Bégin

Saint-Mandé, Val-de-Marne, France

Site Status RECRUITING

Institut Gustave Roussy

Villejuif, Val-de-Marne, France

Site Status RECRUITING

Centre Hospitalier d'Auxerre

Auxerre, Yonne, France

Site Status RECRUITING

Hôpital Pitié-Salpêtrière - APHP

Paris, , France

Site Status RECRUITING

Hôpital Cochin - APHP

Paris, , France

Site Status RECRUITING

Hôpital Tenon - APHP

Paris, , France

Site Status RECRUITING

Hôpital Paris Saint-Joseph

Paris, , France

Site Status RECRUITING

H. Santa Creu i Sant Pau

Barcelona, , Spain

Site Status RECRUITING

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, , Spain

Site Status RECRUITING

H. Clinico San Carlos

Madrid, , Spain

Site Status RECRUITING

HU. 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Hospital Virgen de la Victoria

Málaga, , Spain

Site Status RECRUITING

H.Virgen del Rocio

Seville, , Spain

Site Status RECRUITING

Countries

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Belgium France Spain

Central Contacts

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Benjamin BESSE

Role: CONTACT

+33(0)1 42 11 62 61

Lynda MATI

Role: CONTACT

+33(0)1 42 11 37 30

Facility Contacts

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Vincent VAHHAUDENARDE, MD

Role: primary

Lynda MATI

Role: backup

0033 142113730

LABOUREY Jean Luc, MD

Role: primary

Lynda MATI

Role: backup

0142113730

TAZI Youssef, MD

Role: primary

Lynda MATI

Role: backup

0142113730

SCHOTT Rolland, MD

Role: primary

Lynda MATI

Role: backup

0142113730

LE TREUT Jacques, md

Role: primary

Lynda MATI

Role: backup

0142113730

LEVRAT Virginie, MD

Role: primary

Lynda MATI

Role: backup

0142113730

QUERE Gilles, MD

Role: primary

Lynda MATI

Role: backup

0142113730

AMRANE Karim, MD

Role: primary

Lynda MATI

Role: backup

0142113730

DEBIEUVRE Dédier, MD

Role: primary

Lynda MATI

Role: backup

0142113730

DEGUIRAL Philippe, MD

Role: primary

Lynda MATI

Role: backup

0142113730

METIVIER Anne Cécile, MD

Role: primary

Lynda MATI

Role: backup

0142113730

HAOUACHI Rym, MD

Role: primary

Lynda MATI

Role: backup

0142113730

RICORDEL Charles, MD

Role: primary

Lynda MATI

Role: backup

0142113730

TIERCIN Marie, MD

Role: primary

Lynda MATI

Role: backup

0142113730

CARMIER Delphine, MD

Role: primary

Lynda MATI

Role: backup

0142113730

GAZAILLE Virgile, MD

Role: primary

Lynda MATI

Role: backup

0142113730

HUCHOT Eric, MD

Role: primary

Lynda MATI

Role: backup

0142113730

DIXMIER Adrien, MD

Role: primary

Lynda MATI

Role: backup

0142113730

DURUISSEAUX Michaël, MD

Role: primary

Lynda MATI

Role: backup

0142113730

GUILLEMOIS Sylvère, MD

Role: primary

Lynda MATI

Role: backup

0142113730

DEHETTE Stéphanie, MD

Role: primary

Lynda MATI

Role: backup

0142113730

FOURNEL Pierre, MD

Role: primary

Lynda MATI

Role: backup

0142113730

SCHNEIDER Sophie, MD

Role: primary

Lynda MATI

Role: backup

0142113730

MONNET Isabelle, MD

Role: primary

Lynda MATI

Role: backup

0142113730

HELISSEY Carole, MD

Role: primary

Lynda MATI

Role: backup

0142113730

Benjamin BESSE

Role: primary

+33 (0)1 42 11 62 61

MARTI Adina, MD

Role: primary

Lynda MATI

Role: backup

0142113730

SPANO Jean-Philippe, MD

Role: primary

Lynda MATI

Role: backup

0142113730

WISLEZ Marie, MD

Role: primary

Lynda MATI

Role: backup

0142113730

CADRANEL Jacques, MD

Role: primary

Lynda MATI

Role: backup

0142113730

NALTET Charles, MD

Role: primary

Lynda MATI

Role: backup

0142113730

Andrés BARBA JOAQUIN, MD

Role: primary

Lynda MATI

Role: backup

0033 142113730

Nuria PARDO ARANDA, MD

Role: primary

Lynda MATI

Role: backup

0033 142113730

Carlos AGUADO DE LA ROSA, MD

Role: primary

Lynda MATI

Role: backup

0033 142113730

Jon Zugazagoitia, MD

Role: primary

Lynda MATI

Role: backup

0033 142113730

José Carlos Benítez Montañez, MD

Role: primary

Lynda MATI

Role: backup

0033 142113730

Reyes BERNABE CARO, MD

Role: primary

Lynda MATI

Role: backup

0033 142113730

Other Identifiers

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2021/3336

Identifier Type: OTHER

Identifier Source: secondary_id

2023-503481-23-00

Identifier Type: CTIS

Identifier Source: secondary_id

2021-006795-16

Identifier Type: -

Identifier Source: org_study_id

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