Non-small-cell Lung CancerPhase 3PERSEENCT04547504
PEmbRolizumab verSus chEmotherapy and pEmbrolizumab in Non-small-cell Lung Cancers (NSCLC) With PDL1 ≥ 50 %
A Phase 3 study testing Pembrolizumab and Pembrolizumab and Chemotherapy drugs in people with Non-small-cell Lung Cancer, run by University Hospital, Brest at 29 sites in France.
Trial summary
PERSEE is a French national phase 3 academic study comparing the chemotherapy-pembrolizumab combination to pembrolizumab alone as a first-line treatment for advanced NSCLC molecularly defined by a PDL1 expression ≥ 50% of tumour cells and no EGFR mutations or ALK rearrangement. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small-cell Lung Cancer
- What is being tested?
- Pembrolizumab and Pembrolizumab and Chemotherapy drugs
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 349 participants
- Where
- 29 sitesFrance
- Study dates
- 22 Dec 2020to 22 Dec 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older at diagnosis.
- Histologically or cytologically confirmed NSCLC.
- Stage IV NSCLC. Unresectable and non-eligible to radiotherapy stage III NSCLC are permitted.
- For non-squamous NSCLCs and non-smoking squamous NSCLCs, no known activating mutations of EGFR and no ALK or ROS-1 rearrangements.
- PD-L1 expression on ≥ 50 % of tumor cells, which will be determined locally.
- No prior systemic treatment for lung cancer. Patients who received adjuvant therapy are eligible if the adjuvant therapy was completed at least 12 months prior to the development of metastatic disease.
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- Palliative radiotherapy completed within one day before randomization (stereotaxic or not) is authorized.
- At least 1 target lesion in a non-irradiated area, measurable according to RECIST v1.1.
- An Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
- Life expectancy >12 weeks.
- Patients with brain metastases at inclusion are accepted, provided that these metastases are asymptomatic, or symptomatic but treated (surgery or radiotherapy without or with corticosteroids ≤10 mg/day), and that they are stable on the day of inclusion.
- No history of other malignant tumor during the previous 5 years, except for adequately treated carcinomas (in situ cervical carcinoma, basal cell carcinoma, squamous cell skin carcinoma) and low grade localized prostate cancer (Gleason <6).
- Adequate organ function, as demonstrated by laboratory results within 7 days prior to the first administration of study treatment:
- Normal hepatic function: bilirubin ≤1.5 x upper limit of normal (ULN), alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) ≤2.5 x ULN or ≤5 x ULN in case of liver metastases
- Normal renal function: calculated creatinine clearance (CrCl, using local formula) of at least 60 mL/min for cisplatin or 45 ml/mn for carboplatin
- Normal hematological function: absolute neutrophil count ≥1.5 giga/L and/or platelets ≥100 giga/L, hemoglobin ≥8 g/dL
- Normal coagulation function: International Normalized Ratio (INR) or prothrombin time ≤1.5 x ULN and activated partial thromboplastin time (aPTT) ≤1.5 x ULN unless the patient is receiving anticoagulant therapy.
- For patients of childbearing potential: use of an adequate method of contraception during the course of the study through 180 days after the last dose of study treatment (women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to the first administration of study treatment).
- Note: Abstinence is acceptable if this is the usual lifestyle and the patient's preferred contraception. For male subjects, male condom or abstinence are acceptable.
- Signed informed consent to participate in the study
- Affiliation with or benefit from French social security.
Who cannot join
- NSCLC with expression of PD-L1 <50%.
- NSCLC with known activating mutation of EGFR or ALK or ROS-1 translocation.
- Neuroendocrine tumor. In cases of mixed tumors, if small cell elements are present, the patient is ineligible.
- Any previous treatment with immunotherapy regardless of the line of treatment.
- Before the first dose of study treatment:
- Has received prior systemic treatment for metastatic disease (chemotherapy or targeted therapy).
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- Had major surgery <3 weeks prior to first dose.
- Received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study treatment.
- Uncontrolled and untreated superior cava syndrome.
- Untreated and unstable symptomatic brain metastases.
- Leptomeningeal disease.
- Serious concurrent conditions during the previous 6 months (severe or unstable angina pectoris, coronary or peripheral artery bypass graft of <6 months, class 3 or 4 congestive heart failure, ischemic stroke, grade ≥2 peripheral neuropathy, psychiatric or neurological disorders that may interfere with the patient's understanding of the study or with his/her informed consent.
- Severe or non controlled systemic diseases deemed incompatible with the protocol.
- Severe infections within 4 weeks prior to inclusion, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
- Other previous or concomitant cancers, with the exception of basal cell carcinoma, squamous cell skin carcinoma, in situ cervical carcinoma treated, and low grade localized prostate cancer (Gleason score <6) if appropriately treated, unless the initial tumor has been diagnosed and definitively treated >5 years prior to the study, with no signs of relapse.
- Psychological, family, social, or geographical factors that may interfere with the monitoring of the patient as defined by the protocol.
- Any protected person (legal person protected by legal protection [guardianship, tutorship], person deprived of liberty, pregnant woman, breastfeeding woman, and minor).
- Patients who participated in other concomitant studies unless observational and received study therapy or used an investigational device within 4 weeks prior to start of study treatment.
- Known or suspected active autoimmune disease requiring an immunosuppressive therapy during the previous 6 months (corticosteroids or other immunosuppressive treatment). Any hormone replacement therapy (i.e. thyroxine [T4], insulin, or replacement systemic corticosteroids for adrenal or pituitary insufficiency, etc.) is not considered an immunosuppressive treatment and is authorized. Patients with hyperthyroidism or hypothyroidism who are stable under hormone replacement therapy may also be included.
- Chronic use of immunosuppressive drugs and/or corticosteroids (>10 mg of prednisone daily). However, during the 14 days prior to randomization the use of the following is authorized:
- Corticosteroids as pre treatment for the administration of chemotherapy and/or for allergies or type IV hypersensitivity responses
- Daily prednisone (≤10 mg) as replacement therapy
- Inhaled or topical steroids.
- Live-virus vaccination within 30 days of planned start of study treatment (seasonal flu vaccines that do not contain live virus are permitted).
- Previous allogenic tissue or organ transplant.
- History of human immunodeficiency virus (HIV) infection (positive HIV1/2 antibody test results).
- Active hepatitis B or C.
- Previous history of interstitial lung disease (ILD) or non infectious pneumonia (other than chronic obstructive pulmonary disease [COPD]), requiring oral or systemic steroids, current pneumonia, or anticipated ILD.
- Known allergies or adverse reactions to the study drugs or hypersensitivity reaction to treatment with another monoclonal antibody (mAb).
Trial locations and contacts
29 sites in 1 country.
29 sites in 1 country
France29 sites
CH du Pays d'Aix
Aix-en-Provence, 13616
CHU AMIENS - Hôpital Sud
Amiens, 80054
Chu Angers
Angers, 49033
CHRU de Brest
Brest, 29609
Centre de lutte contre le cancer - Centre François Baclesse
Caen, 14000
Centre Hospitalier Métropole Savoie
Chambéry, 73000
CH Intercommunal de Créteil
Créteil, 94010
CH La Roche Sur Yon - CHD Les Oudairies
La Roche-sur-Yon, 85000
Chu Dupuytren
Limoges, 87042
CH de Lorient - Hôpital du Scorff
Lorient, 56100
Centre Léon Berard
Lyon, 69008
Institut Paoli-Calmette
Marseille, 13000
Hôpital Européen Marseille
Marseille, 13003
CHU MARSEILLE_ Hopital Nord
Marseille, 13915
CH MEAUX
Meaux, 77108
APHP - Hôpital Cochin
Paris, 75014
CHU Bordeaux - Hôpital du Haut Levêque
Pessac, 33604
CH d'Annecy-genevois
Pringy, 74374
Centre Hospitalier de Cornouaille
Quimper, 29000
CHU RENNES - Hôpital Pontchailloux
Rennes, 35033
CHU ROUEN - Hôpital Charles Nicolle
Rouen, 76031
Saint Aubin Les Elbeuf
Saint-Aubin-lès-Elbeuf, 76503
CH La Réunion - Site Félix Guyon
Saint-Denis, 97400
CHU La Réunion - Groupe Hospitalier Sud
Saint-Pierre, 97410
SAINT-PRIEST EN JAREZ - Institut de Cancérologie de la Loire
Saint-Priest-en-Jarez, 42271
Institut de Cancérologie Strasbourg Europe
Strasbourg, 67200
Hôpital d'Instruction des Armées Toulon - Saint Anne
Toulon, 83041
Ch Villefranche Sur Saone
Villefranche-sur-Saône, 69655
Institut Gustave Roussy
Villejuif, 94800
About this study
Official title: Randomized, Open-label, Controlled Phase III Trial Comparing Pembrolizumab-platinum Based Chemotherapy Combination With Pembrolizumab Monotherapy in First Line Treatment of Non-small-cell Lung Cancers (NSCLC) With PDL1 Expression ≥50%
PERSEE is a French national phase 3 academic study comparing the chemotherapy-pembrolizumab combination to pembrolizumab alone as a first-line treatment for advanced NSCLC molecularly defined by a PDL1 expression ≥ 50% of tumour cells and no EGFR mutations or ALK rearrangement.
The main hypothesis is the superiority of the chemo-immunotherapy combination over mono-immunotherapy in terms of progression-free survival evaluated by an independent review committee.
One of the anticipated benefits of using the chemotherapy-pembrolizumab combination starting from the first line setting for NSCLC patients with PD L1 ≥ 50% is a reduced risk of early progression, which is known to occur with pembrolizumab monotherapy, and therefore, a better PFS.
Read the detailed description
PERSEE is a french academic, prospective, randomized, controlled and open-label phase 3 study. This trial compares the combination of chemotherapy and pembrolizumab with pembrolizumab alone as first-line treatment for advanced NSCLC molecularly characterized by a PDL1 expression level ≥ 50% and no EGFR mutations or ALK rearrangement. This is a strategy trial whose primary objective is to evaluate the superiority of the chemotherapy-pembrolizumab combination over pembrolizumab using PFS as the primary endpoint as evaluated by an independent review committee.
PERSEE trial is planned to include 292 patients treated at approximately 30 GFPC-affiliated or GFPC-associated centres. After the screening period, patients will be randomized on a 1:1 basis to the Chemotherapy Immunotherapy Arm or the Immunotherapy Arm. Randomization will be stratified according to tumor histology (squamous versus non squamous) and according to the presence or absence of brain metastases. Patients enrolled in this study will receive either of the following treatment regimens:
- Chemotherapy-Immunotherapy Arm: Four induction cycles once every 3 weeks associating, on the first day of each cycle:
- Cisplatin 75 mg/m² or carboplatin area under the curve (AUC) 5 mg/mL/min, pemetrexed 500 mg/m² and pembrolizumab 200 mg for non-squamous NSCLC.
- Carboplatin AUC 6 mg/mL/min, paclitaxel 200 mg/m² and pembrolizumab 200 mg for squamous NSCLC. After the 4 induction cycles, a maintenance therapy will be possible for patients who are responding or stable, as follows:
- Non squamous NSCLC: pembrolizumab and pemetrexed combination or either drug as monotherapy (if toxicity has been identified for one of them).
- Squamous NSCLC: pembrolizumab monotherapy. For pembrolizumab: treatment may be continued for a maximum of 35 cycles or until disease progression, death, unacceptable toxicity, or following the Investigator's or the patient's decision to stop. For pemetrexed, treatment may be continued until disease progression, death, unacceptable toxicity, or following the Investigator's or the patient's decision to stop.
- Immunotherapy Arm:
Pembrolizumab 200 mg once every 3 weeks for a maximum of 35 cycles or until disease progression, death, unacceptable toxicity, or the Investigator's or the patient's decision to stop.
Evaluations will be performed every 6 weeks (±7 days) during the first 4 cycles in both treatment arms, then every 9 weeks (±7 days) for the first 12 months since D1 of cycle 1 and every 12 weeks (±7 days) thereafter.
Evaluations will include: tumor assessment according to RECIST v1.1, survival status, concomitant medications and AE recording. QoL/PRO questionnaires will be performed at each cycle for the first 5 cycles in both treatment arms, then every 9 weeks (±7 days) for the first 12 months since D1 of cycle 1 and every 12 weeks (±7 days) thereafter.
The length of the inclusion period is 36 months (3 years). The total study duration per patient will be a maximum of two years for the last patients included, and a maximum of five years for the first patients included (i.e. End-of-study Time Point for surviving patients)
The total study duration includes the following:
- Screening Period: up to 28 days.
- Treatment Period: up to 60 months.
- Post-study Follow up Period: until death or lost to follow-up.
- Conditions
- Non-small-cell Lung Cancer
- Being tested
- Pembrolizumab, Pembrolizumab and Chemotherapy drugs
- Keywords
- Non-small-cell lung cancer, PDL1≥50%, advanced stage, Pembrolizumab, Chemotherapy-pembrolizumab combination
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Pembrolizumab 200 mg once every 3 weeks for a maximum of 35 cycles or until disease progression, death, unacceptable toxicity, or the Investigator's or the patient's decision to stop.
Pembrolizumab and Chemotherapy drugsDrug
An induction therapy followed by a maintenance therapy.
4 induction cycles every 3 weeks associating, on the first day of each cycle:
- Cisplatin 75mg/m² or carboplatin AUC 5mg/mL/min, pemetrexed 500mg/m² and pembrolizumab 200mg for non squamous NSCLC.
- Carboplatin AUC 6mg/mL/min, paclitaxel 200mg/m² and pembrolizumab 200mg for squamous NSCLC.
After the 4 induction cycles, a maintenance therapy will be possible for patients who are responding or stable:
- Non squamous NSCLC: pembrolizumab and pemetrexed combination or either drug as monotherapy.
- Squamous NSCLC: pembrolizumab monotherapy.
For pembrolizumab: treatment may be continued for a maximum of 35 cycles or until disease progression, death, unacceptable toxicity, or following the Investigator's or the patient's decision to stop.
For pemetrexed, treatment may be continued until disease progression, death, unacceptable toxicity, or following the Investigator's or the patient's decision to stop.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Active comparator | Pembrolizumab Receives: Drug: Pembrolizumab |
| Chemotherapy-Pembrolizumab | Active comparator | Chemotherapy and Pembrolizumab Receives: Drug: Pembrolizumab and Chemotherapy drugs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS) according to RECIST 1.1 assessed by blinded inependant centra review (BICR)
Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, according to RECIST 1.1 assessed by blinded inependant centra review (BICR)
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Secondary outcomes (15)
Progression-free survival according to RECIST 1.1 evaluated by investigators
Time from date of randomization until the date of first documented progression or death from any cause, whichever came first, according to RECIST v1.1 and evaluated by investigators
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Progression-free survival according to iRECIST assessed by blinded inependant centra review (BICR)
Time from date of randomization until the date of first documented progression or death from any cause, whichever came first, according to iRECIST assessed by blinded inependant centra review (BICR)
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first assessed up to 60 months
Objective Response Rate (ORR)
Proportion of patients who achieved a complete response (CR) or partial response (PR) according to RECIST v1.1 from the date of first treatment administration until disease progression or the introduction of a new treatment.
Measured: From date of first treatment administration until the date of first documented progression or death or the introduction of a new treatment, whichever came first, assessed up to 60 months
Overall survival (OS)
Time from date of randomization until the date of death from any cause.
Measured: From date of randomization until the date of death from any cause assessed up to 60 months
Duration of treatment (DOT)
Time from the first treatment administration until the date of last treatment administration.
Measured: From date of the first treatment administration until the date of last treatment administration, up to 60 months
Duration of objective response (DOR)
Time from the first documented objective response (CR or PR) until the date of disease progression or death, whichever came first.
Measured: From date of the first documented objective response (CR or PR) until the date of first documented progression or death from any cause, whichever came first, assessed up to 60 months
Adverse events (AE)
Proportion (%) of patients with any adverse event (AE) and number of events per treatment arm for all AEs, all serious AEs (SAEs) and all AEs of grade ≥3 according to the National Cancer Institute (NCI) Common terminology criteria for adverse events (CTCAE) v5.0 criteria.
Measured: Up to 30 days after the last dose of study treatment for non-serious AEs. Up to 100 days or 30 days if initiating new treatment, after the last dose, for SAE.
Adverse events of special interest (AESI)
Proportion (%) of patients with any adverse event of special interest (AESI), defined as immune-related AE (IrAE), according to the National Cancer Institute (NCI) Common terminology criteria for adverse events (CTCAE) v5.0 criteria. .
Measured: Up to 100 days or 30 days if initiating new treatment, after the last dose.
PFS in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Time from date of randomization until the date of first documented progression or death from any cause, whichever came first, according to RECIST v1.1
Measured: From date of randomization until the date of first documented progression or death from any cause, whichever came first, assessed up to 60 months
OS in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Time from randomization until the date of death from any cause.
Measured: From date of randomization until the date of death from any cause assessed up to 60 months
ORR in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Proportion of patients who achieved a complete response (CR) or partial response (PR) according to RECIST v1.1
Measured: From date of first treatment administration until the date of first documented progression or death or the introduction of a new treatment, whichever came first, assessed up to 60 months
DOR in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Time from the first documented objective response (CR or PR) until the date of disease progression or death, whichever came first.
Measured: From date of the first documented objective response (CR or PR) until the date of first documented progression or death from any cause, whichever came first, assessed up to 60 months
DOT in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Time from the first treatment administration until the date of last treatment administration.
Measured: From date of the first treatment administration until the date of last treatment administration, assessed up to 60 months
AE in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Proportion (%) of patients with any adverse event (AE) and number of events per treatment arm for all AEs, all serious AEs (SAEs) and all AEs of grade ≥3 according to the National Cancer Institute (NCI) Common terminology criteria for adverse events (CTCAE) v5.0 criteria.
Measured: Up to 30 days after the last dose of study treatment for non-serious AEs. Up to 100 days or 30 days if initiating new treatment, after the last dose, for SAE.
AESI in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Proportion (%) of patients with any adverse event (AE) and number of events per treatment arm for all AEs, all serious AEs (SAEs) and all AEs of grade ≥3 according to the National Cancer Institute (NCI) Common terminology criteria for adverse events (CTCAE) v5.0 criteria.
Measured: Up to 100 days or 30 days if initiating new treatment, after the last dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2020
- Study start22 Dec 2020
- Primary completion22 Dec 2025 (estimated)
- Study completion22 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-small-cell Lung CancerStudies of the same condition, open and under way.
- More trials run by University Hospital, BrestThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A national, multicenter, phase III, prospective, open label, 1:1 randomized, interventional study
- Masking
- None (open label)
- Enrolment
- 349 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Brest
- Sponsor type
- University, hospital or other
- Collaborators
- Groupe Francais De Pneumo-Cancerologie
- Responsible party
- Sponsor
- Investigators
- Renaud DESCOURT, MD, Principal investigator, Institut de Cancérologie, CHU Brest, Hôpital MorvanChantal DECROISETTE, MD, Principal investigator, Medical Oncology, Centre Léon Bérard, LyonChristos CHOUAID, MD, PhD, Study director, Service de pneumologie, CH intercommunal de Créteil
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04547504
- Sponsor's protocol ID
- 29BRC20.0159_GFPC01-2020
- Other IDs
- GFPC 01-2020
- Acronym
- PERSEE
- Status last verified
- Sep 2025
- First submitted
- 31 Aug 2020
- Last updated
- 17 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected data that underlie results in a publication
Publications
Descourt R, Chouaid C, Perol M, Besse B, Greillier L, Bylicki O, Ricordel C, Guisier F, Gervais R, Schott R, Auliac JB, Robinet G, Decroisette C. First-line pembrolizumab with or without platinum doublet chemotherapy in non-small-cell lung cancer patients with PD-L1 expression >/=50. Future Oncol. 2021 Aug;17(23):3007-3016. doi: 10.2217/fon-2020-1202. Epub 2021 Jun 22.
PubMed 34156285
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Open-label, Controlled Phase III Trial Comparing Pembrolizumab-platinum Based Chemotherapy Combination With Pembrolizumab Monotherapy in First Line Treatment of Non-small-cell Lung Cancers (NSCLC) With PDL1 Expression ≥50%
- ClinicalTrials.gov ID
- NCT04547504
- Acronym / sponsor ID
- PERSEE / 29BRC20.0159_GFPC01-2020
- Conditions
- Non-small-cell Lung Cancer
- Keywords
- Non-small-cell lung cancer, PDL1≥50%, advanced stage, Pembrolizumab, Chemotherapy-pembrolizumab combination
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 349 participants (actual)
- Lead sponsor
- University Hospital, BrestUniversity, hospital or other
- Collaborators
- Groupe Francais De Pneumo-Cancerologie
- Study start
- 22 Dec 2020 (actual)
- Primary completion
- 22 Dec 2025 (estimated)
- Study completion
- 22 Dec 2025 (estimated)
- First posted
- 14 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
PERSEE is a French national phase 3 academic study comparing the chemotherapy-pembrolizumab combination to pembrolizumab alone as a first-line treatment for advanced NSCLC molecularly defined by a PDL1 expression ≥ 50% of tumour cells and no EGFR mutations or ALK rearrangement.
The main hypothesis is the superiority of the chemo-immunotherapy combination over mono-immunotherapy in terms of progression-free survival evaluated by an independent review committee.
One of the anticipated benefits of using the chemotherapy-pembrolizumab combination starting from the first line setting for NSCLC patients with PD L1 ≥ 50% is a reduced risk of early progression, which is known to occur with pembrolizumab monotherapy, and therefore, a better PFS.
Detailed description
PERSEE is a french academic, prospective, randomized, controlled and open-label phase 3 study. This trial compares the combination of chemotherapy and pembrolizumab with pembrolizumab alone as first-line treatment for advanced NSCLC molecularly characterized by a PDL1 expression level ≥ 50% and no EGFR mutations or ALK rearrangement. This is a strategy trial whose primary objective is to evaluate the superiority of the chemotherapy-pembrolizumab combination over pembrolizumab using PFS as the primary endpoint as evaluated by an independent review committee.
PERSEE trial is planned to include 292 patients treated at approximately 30 GFPC-affiliated or GFPC-associated centres. After the screening period, patients will be randomized on a 1:1 basis to the Chemotherapy Immunotherapy Arm or the Immunotherapy Arm. Randomization will be stratified according to tumor histology (squamous versus non squamous) and according to the presence or absence of brain metastases. Patients enrolled in this study will receive either of the following treatment regimens:
- Chemotherapy-Immunotherapy Arm: Four induction cycles once every 3 weeks associating, on the first day of each cycle:
- Cisplatin 75 mg/m² or carboplatin area under the curve (AUC) 5 mg/mL/min, pemetrexed 500 mg/m² and pembrolizumab 200 mg for non-squamous NSCLC.
- Carboplatin AUC 6 mg/mL/min, paclitaxel 200 mg/m² and pembrolizumab 200 mg for squamous NSCLC. After the 4 induction cycles, a maintenance therapy will be possible for patients who are responding or stable, as follows:
- Non squamous NSCLC: pembrolizumab and pemetrexed combination or either drug as monotherapy (if toxicity has been identified for one of them).
- Squamous NSCLC: pembrolizumab monotherapy. For pembrolizumab: treatment may be continued for a maximum of 35 cycles or until disease progression, death, unacceptable toxicity, or following the Investigator's or the patient's decision to stop. For pemetrexed, treatment may be continued until disease progression, death, unacceptable toxicity, or following the Investigator's or the patient's decision to stop.
- Immunotherapy Arm:
Pembrolizumab 200 mg once every 3 weeks for a maximum of 35 cycles or until disease progression, death, unacceptable toxicity, or the Investigator's or the patient's decision to stop.
Evaluations will be performed every 6 weeks (±7 days) during the first 4 cycles in both treatment arms, then every 9 weeks (±7 days) for the first 12 months since D1 of cycle 1 and every 12 weeks (±7 days) thereafter.
Evaluations will include: tumor assessment according to RECIST v1.1, survival status, concomitant medications and AE recording. QoL/PRO questionnaires will be performed at each cycle for the first 5 cycles in both treatment arms, then every 9 weeks (±7 days) for the first 12 months since D1 of cycle 1 and every 12 weeks (±7 days) thereafter.
The length of the inclusion period is 36 months (3 years). The total study duration per patient will be a maximum of two years for the last patients included, and a maximum of five years for the first patients included (i.e. End-of-study Time Point for surviving patients)
The total study duration includes the following:
- Screening Period: up to 28 days.
- Treatment Period: up to 60 months.
- Post-study Follow up Period: until death or lost to follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A national, multicenter, phase III, prospective, open label, 1:1 randomized, interventional study
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Active comparator | Drug: PembrolizumabPembrolizumab |
| Chemotherapy-Pembrolizumab | Active comparator | Drug: Pembrolizumab and Chemotherapy drugsChemotherapy and Pembrolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Age 18 years or older at diagnosis.
- Histologically or cytologically confirmed NSCLC.
- Stage IV NSCLC. Unresectable and non-eligible to radiotherapy stage III NSCLC are permitted.
- For non-squamous NSCLCs and non-smoking squamous NSCLCs, no known activating mutations of EGFR and no ALK or ROS-1 rearrangements.
- PD-L1 expression on ≥ 50 % of tumor cells, which will be determined locally.
Key exclusion criteria (29 listed)
- NSCLC with expression of PD-L1 <50%.
- NSCLC with known activating mutation of EGFR or ALK or ROS-1 translocation.
- Neuroendocrine tumor. In cases of mixed tumors, if small cell elements are present, the patient is ineligible.
- Any previous treatment with immunotherapy regardless of the line of treatment.
- Before the first dose of study treatment:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabPembrolizumab 200 mg once every 3 weeks for a maximum of 35 cycles or until disease progression, death, unacceptable toxicity, or the Investigator's or the patient's decision to stop. | Drug | Pembrolizumab |
| Pembrolizumab and Chemotherapy drugsAn induction therapy followed by a maintenance therapy. 4 induction cycles every 3 weeks associating, on the first day of each cycle: * Cisplatin 75mg/m² or carboplatin AUC 5mg/mL/min, pemetrexed 500mg/m² and pembrolizumab 200mg for non squamous NSCLC. * Carboplatin AUC 6mg/mL/min, paclitaxel 200mg/m² and pembrolizumab 200mg for squamous NSCLC. After the 4 induction cycles, a maintenance therapy will be possible for patients who are responding or stable: * Non squamous NSCLC: pembrolizumab and pemetrexed combination or either drug as monotherapy. * Squamous NSCLC: pembrolizumab monotherapy. For pembrolizumab: treatment may be continued for a maximum of 35 cycles or until disease progression, death, unacceptable toxicity, or following the Investigator's or the patient's decision to stop. For pemetrexed, treatment may be continued until disease progression, death, unacceptable toxicity, or following the Investigator's or the patient's decision to stop. | Drug | Chemotherapy-Pembrolizumab |
Primary outcome
Progression-free survival (PFS) according to RECIST 1.1 assessed by blinded inependant centra review (BICR)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, according to RECIST 1.1 assessed by blinded inependant centra review (BICR)
15 secondary outcomes
Progression-free survival according to RECIST 1.1 evaluated by investigators
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Progression-free survival according to iRECIST assessed by blinded inependant centra review (BICR)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first assessed up to 60 months
Objective Response Rate (ORR)
Time frame: From date of first treatment administration until the date of first documented progression or death or the introduction of a new treatment, whichever came first, assessed up to 60 months
Overall survival (OS)
Time frame: From date of randomization until the date of death from any cause assessed up to 60 months
Duration of treatment (DOT)
Time frame: From date of the first treatment administration until the date of last treatment administration, up to 60 months
Duration of objective response (DOR)
Time frame: From date of the first documented objective response (CR or PR) until the date of first documented progression or death from any cause, whichever came first, assessed up to 60 months
Adverse events (AE)
Time frame: Up to 30 days after the last dose of study treatment for non-serious AEs. Up to 100 days or 30 days if initiating new treatment, after the last dose, for SAE.
Adverse events of special interest (AESI)
Time frame: Up to 100 days or 30 days if initiating new treatment, after the last dose.
PFS in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Time frame: From date of randomization until the date of first documented progression or death from any cause, whichever came first, assessed up to 60 months
OS in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Time frame: From date of randomization until the date of death from any cause assessed up to 60 months
ORR in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Time frame: From date of first treatment administration until the date of first documented progression or death or the introduction of a new treatment, whichever came first, assessed up to 60 months
DOR in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Time frame: From date of the first documented objective response (CR or PR) until the date of first documented progression or death from any cause, whichever came first, assessed up to 60 months
DOT in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Time frame: From date of the first treatment administration until the date of last treatment administration, assessed up to 60 months
AE in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Time frame: Up to 30 days after the last dose of study treatment for non-serious AEs. Up to 100 days or 30 days if initiating new treatment, after the last dose, for SAE.
AESI in three subgroups of patients according to PD-L1 expression (50-74%, 75-100%, and 90-100%), presence or absence of brain metastasis and histology (squamous versus non squamous).
Time frame: Up to 100 days or 30 days if initiating new treatment, after the last dose.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2025.
- Derived from this study: PubMed 34156285Descourt R, Chouaid C, Perol M, Besse B, Greillier L, Bylicki O, Ricordel C, Guisier F, Gervais R, Schott R, Auliac JB, Robinet G, Decroisette C. First-line pembrolizumab with or without platinum doublet chemotherapy in non-small-cell lung cancer patients with PD-L1 expression >/=50. Future Oncol. 2021 Aug;17(23):3007-3016. doi: 10.2217/fon-2020-1202. Epub 2021 Jun 22.
- Individual participant dataSharing planned: Yes. All collected data that underlie results in a publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Renaud DESCOURT, MD principal investigator
Institut de Cancérologie, CHU Brest, Hôpital Morvan
Chantal DECROISETTE, MD principal investigator
Medical Oncology, Centre Léon Bérard, Lyon
Christos CHOUAID, MD, PhD study director
Service de pneumologie, CH intercommunal de Créteil
29 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pembrolizumab and Pembrolizumab and Chemotherapy drugs in people with Non-small-cell Lung Cancer, run by University Hospital, Brest at 29 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) according to RECIST 1.1 assessed by blinded inependant centra review (BICR) (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04547504, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2025.