PEmbRolizumab verSus chEmotherapy and pEmbrolizumab in Non-small-cell Lung Cancers (NSCLC) With PDL1 ≥ 50 %

NCT ID: NCT04547504

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 349 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-22
• Study Completion Date: 2025-12-22

Brief 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.

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:

1. 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.

2. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab

Pembrolizumab

Group Type: ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type: DRUG

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.

Chemotherapy-Pembrolizumab

Chemotherapy and Pembrolizumab

Group Type: ACTIVE_COMPARATOR

Pembrolizumab and Chemotherapy drugs

Intervention Type: DRUG

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.

Interventions

Pembrolizumab

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.

Intervention Type: DRUG

Pembrolizumab and Chemotherapy drugs

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age 18 years or older at diagnosis.

2. Histologically or cytologically confirmed NSCLC.

3. Stage IV NSCLC. Unresectable and non-eligible to radiotherapy stage III NSCLC are permitted.

4. For non-squamous NSCLCs and non-smoking squamous NSCLCs, no known activating mutations of EGFR and no ALK or ROS-1 rearrangements.

5. PD-L1 expression on ≥ 50 % of tumor cells, which will be determined locally.

6. 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.

7. Palliative radiotherapy completed within one day before randomization (stereotaxic or not) is authorized.

8. At least 1 target lesion in a non-irradiated area, measurable according to RECIST v1.1.

9. An Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.

10. Life expectancy >12 weeks.

11. 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.

12. 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).

13. Adequate organ function, as demonstrated by laboratory results within 7 days prior to the first administration of study treatment:

1. 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

2. Normal renal function: calculated creatinine clearance (CrCl, using local formula) of at least 60 mL/min for cisplatin or 45 ml/mn for carboplatin

3. Normal hematological function: absolute neutrophil count ≥1.5 giga/L and/or platelets ≥100 giga/L, hemoglobin ≥8 g/dL

4. 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.

14. 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.

15. Signed informed consent to participate in the study

16. Affiliation with or benefit from French social security.

Exclusion Criteria

1. NSCLC with expression of PD-L1 <50%.

2. NSCLC with known activating mutation of EGFR or ALK or ROS-1 translocation.

3. Neuroendocrine tumor. In cases of mixed tumors, if small cell elements are present, the patient is ineligible.

4. Any previous treatment with immunotherapy regardless of the line of treatment.

5. Before the first dose of study treatment:

1. Has received prior systemic treatment for metastatic disease (chemotherapy or targeted therapy).

2. Had major surgery <3 weeks prior to first dose.

3. Received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study treatment.

6. Uncontrolled and untreated superior cava syndrome.

7. Untreated and unstable symptomatic brain metastases.

8. Leptomeningeal disease.

9. 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.

10. Severe or non controlled systemic diseases deemed incompatible with the protocol.

11. Severe infections within 4 weeks prior to inclusion, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.

12. 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.

13. Psychological, family, social, or geographical factors that may interfere with the monitoring of the patient as defined by the protocol.

14. Any protected person (legal person protected by legal protection [guardianship, tutorship], person deprived of liberty, pregnant woman, breastfeeding woman, and minor).

15. 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.

16. 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.

17. 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:

1. Corticosteroids as pre treatment for the administration of chemotherapy and/or for allergies or type IV hypersensitivity responses

2. Daily prednisone (≤10 mg) as replacement therapy

3. Inhaled or topical steroids.

18. Live-virus vaccination within 30 days of planned start of study treatment (seasonal flu vaccines that do not contain live virus are permitted).

19. Previous allogenic tissue or organ transplant.

20. History of human immunodeficiency virus (HIV) infection (positive HIV1/2 antibody test results).

21. Active hepatitis B or C.

22. 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.

23. Known allergies or adverse reactions to the study drugs or hypersensitivity reaction to treatment with another monoclonal antibody (mAb).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Groupe Francais De Pneumo-Cancerologie

OTHER

Sponsor Role: collaborator

University Hospital, Brest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Renaud DESCOURT, MD

Role: PRINCIPAL_INVESTIGATOR

Institut de Cancérologie, CHU Brest, Hôpital Morvan

Chantal DECROISETTE, MD

Role: PRINCIPAL_INVESTIGATOR

Medical Oncology, Centre Léon Bérard, Lyon

Christos CHOUAID, MD, PhD

Role: STUDY_DIRECTOR

Service de pneumologie, CH intercommunal de Créteil

Locations

CH du Pays d'Aix

Aix-en-Provence, , France

CHU AMIENS - Hôpital Sud

Amiens, , France

Chu Angers

Angers, , France

CHRU de Brest

Brest, , France

Centre de lutte contre le cancer - Centre François Baclesse

Caen, , France

Centre Hospitalier Métropole Savoie

Chambéry, , France

CH Intercommunal de Créteil

Créteil, , France

CH La Roche Sur Yon - CHD Les Oudairies

La Roche-sur-Yon, , France

Chu Dupuytren

Limoges, , France

CH de Lorient - Hôpital du Scorff

Lorient, , France

Centre Léon Berard

Lyon, , France

Institut Paoli-Calmette

Marseille, , France

Hôpital Européen Marseille

Marseille, , France

CHU MARSEILLE_ Hopital Nord

Marseille, , France

CH MEAUX

Meaux, , France

APHP - Hôpital Cochin

Paris, , France

CHU Bordeaux - Hôpital du Haut Levêque

Pessac, , France

CH d'Annecy-genevois

Pringy, , France

Centre Hospitalier de Cornouaille

Quimper, , France

CHU RENNES - Hôpital Pontchailloux

Rennes, , France

CHU ROUEN - Hôpital Charles Nicolle

Rouen, , France

Saint Aubin Les Elbeuf

Saint-Aubin-lès-Elbeuf, , France

CH La Réunion - Site Félix Guyon

Saint-Denis, , France

CHU La Réunion - Groupe Hospitalier Sud

Saint-Pierre, , France

SAINT-PRIEST EN JAREZ - Institut de Cancérologie de la Loire

Saint-Priest-en-Jarez, , France

Institut de Cancérologie Strasbourg Europe

Strasbourg, , France

Hôpital d'Instruction des Armées Toulon - Saint Anne

Toulon, , France

Ch Villefranche Sur Saone

Villefranche-sur-Saône, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 34156285 (View on PubMed)

Other Identifiers

GFPC 01-2020

Identifier Type: OTHER

Identifier Source: secondary_id

29BRC20.0159_GFPC01-2020

Identifier Type: -

Identifier Source: org_study_id