Clinical Trials /

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

NCT04547504

Description:

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.

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 29BRC20.0159_GFPC01-2020
  • SECONDARY ID: GFPC 01-2020
  • NCT ID: NCT04547504

Conditions

  • Non-small-cell Lung Cancer

Interventions

DrugSynonymsArms
PembrolizumabPembrolizumab
Pembrolizumab and Chemotherapy drugsChemotherapy-Pembrolizumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
PembrolizumabActive ComparatorPembrolizumab
  • Pembrolizumab
Chemotherapy-PembrolizumabActive ComparatorChemotherapy and Pembrolizumab
  • Pembrolizumab and Chemotherapy drugs

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) or partial
                  thromboplastin time (PTT) ≤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 2 years (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 (5 mg to 7.5 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. Patients who are receiving denosumab prior to inclusion must be willing and eligible
             to discontinue its use and replace it with a bisphosphonate instead.

         20. Previous allogenic tissue or organ transplant.

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

         22. Active hepatitis B or C.

         23. 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.

         24. Known allergies or adverse reactions to the study drugs or hypersensitivity reaction
             to treatment with another monoclonal antibody (mAb).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) according to RECIST 1.1 centrally reviewed by an expert panel of clinicians
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
Safety Issue:
Description: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 and centrally reviewed by an expert panel of clinicians

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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
Measure:Progression-free survival according to iRECIST evaluated by an expert panel of clinicians (iPFS)
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
Safety Issue:
Description:Time from date of randomization until the date of first documented progression or death from any cause, whichever came first, according to iRECIST evaluated by an expert panel of clinicians (iPFS).
Measure: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
Safety Issue:
Description: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.
Measure:Overall survival (OS)
Time Frame:From date of randomization until the date of death from any cause assessed up to 60 months
Safety Issue:
Description:Time from date of randomization until the date of death from any cause.
Measure:Duration of treatment (DOT)
Time Frame:From date of the first treatment administration until the date of last treatment administration, up to 60 months
Safety Issue:
Description:Time from the first treatment administration until the date of last treatment administration.
Measure: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
Safety Issue:
Description:Time from the first documented objective response (CR or PR) until the date of disease progression or death, whichever came first.
Measure: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.
Safety Issue:
Description: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.
Measure:Adverse events of special interest (AESI)
Time Frame:Up to 100 days or 30 days if initiating new treatment, after the last dose.
Safety Issue:
Description: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. .
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description:Time from randomization until the date of death from any cause.
Measure: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
Safety Issue:
Description:Proportion of patients who achieved a complete response (CR) or partial response (PR) according to RECIST v1.1
Measure: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
Safety Issue:
Description:Time from the first documented objective response (CR or PR) until the date of disease progression or death, whichever came first.
Measure: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
Safety Issue:
Description:Time from the first treatment administration until the date of last treatment administration.
Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University Hospital, Brest

Trial Keywords

  • Non-small-cell lung cancer
  • PDL1≥50%
  • advanced stage
  • Pembrolizumab
  • Chemotherapy-pembrolizumab combination

Last Updated

September 14, 2020