Double Immune Checkpoint Inhibitors in PD-L1-positive Stage IV Non-small Lung CancEr

NCT ID: NCT03469960

Last Updated: 2025-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 265 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-02
• Study Completion Date: 2025-10-15

Brief Summary

Non Small Cell lung cancer (NSCLC) remains the first cause of death by cancer in the World. For the patients presenting a NSCLC stage IV, the median of survival is about 15 months today. The chemotherapy with platinum is the standard treatment for these patients but immunotherapy showed these efficacy in 1st line for patients PD-L1 positive. On the other hand, the duration of treatment by immunotherapy is not clear. Indeed, prolonged responses and long survivals have been described in patients having interrupted the treatment. In the melanoma, a treatment of 6 months of ipilimumab demonstrated its efficacy. The objective of the study is to demonstrate that a treatment of 6 months followed by an observation (stop and go) is not less effective than a treatment given until progression or toxicity. This strategy would allow to decrease the accumulated toxicities, to improve the quality of life of the patients and to decrease the costs.

Conditions

Non-Small Cell Lung Cancer Metastatic

Study Design

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

Study Groups

Arm A : standard treatment

6 months of treatment by nivolumab + ipilimumab then nivolumab + ipilimumab then in case of progression platinum-based doublet recommended

Group Type: ACTIVE_COMPARATOR

Ipilimumab

Intervention Type: DRUG

Ipilimumab 1 mg/kg every 6 weeks

Nivolumab

Intervention Type: DRUG

Nivolumab 3 mg/kg every 2 weeks

Arm B : experimental arm

6 months of treatment by nivolumab + ipilimumab then observation the in case of progression nivolumab + ipilimumab then in case of progression platinum-based doublet recommended

Group Type: EXPERIMENTAL

Ipilimumab

Intervention Type: DRUG

Ipilimumab 1 mg/kg every 6 weeks

Nivolumab

Intervention Type: DRUG

Nivolumab 3 mg/kg every 2 weeks

Interventions

Ipilimumab

Ipilimumab 1 mg/kg every 6 weeks

Intervention Type: DRUG

Nivolumab

Nivolumab 3 mg/kg every 2 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Signed Written Informed Consent:

Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.

Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.

2. Histologically-proven NSCLC (squamous or non-squamous)

3. Stage IV (M1, including M1a pleural involvement) disease (8th classification TNM, UICC 2015)

4. ECOG PS < 1

5. Weight loss< 10% in previous 3 months

6. No prior systemic anticancer therapy (including EGFR or ALK inhibitors) given as primary therapy for advanced or metastatic disease.

7. Age≥ 18 years, <75 years

8. Life expectancy > 3 months

9. Measurable tumor disease by CT or MRI per RECIST 1.1 criteria

10. Available tumor samples for centralized PD-L1 immunohistochemistry analysis

11. PD-L1 tumor content ≥ 1% and < 50% tumor cells as assessed locally by the investigator center

12. Adequate biological functions:

Creatinine Clearance ≥ 50 mL/min (Cockcroft or MDRD or CKD-epi); neutrophiles ≥ 1500/mm3 ; platelets ≥100 000/mm3 ; Hemoglobin ≥ 9g/dL ; hepatic enzymes < 3x ULN, total bilirubin ≤ 1,5 x ULN except for patients with proved, Gilbert syndrome (≤ 5 x ULN) or patients with hepatic metastases (≤ 3,0 mg/dL)

13. Women of childbearing potential (WOCBP) and sexually active should use an efficacious contraception method within the 28 days preceding the first dose and during the 6 months following the last dose of treatment. Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.

For Male subjects who are sexually active with WOCBP, an efficacious contraception method should be used during the treatment and during the 7 months following the last dose.

Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly. At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective.

14. Patient inclusion validated by a multidisciplinary meeting.

Exclusion Criteria

1. Small cell lung cancer or tumors with mixt histology including a SCLC component

2. Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R ou L861X mutations in exon 21, G719A/S mutation in exon 18) or HER exon 20 insertion (either tissue or plasma cfDNA mutation).

3. Known ALK or ROS1 gene rearrangement as assessed by immunohistochemistry, FISH or NGS sequencing

4. Previous or active cancer within the previous 5 years (except for treated carcinoma in situ of the cervix or basal cell skin cancer). Patients with a prostate adenocarcinoma history within the previous 5 years could be included in case of localized prostate cancer, with good prognostic factors according to d'Amico classification (≤ T2a and Score de Gleason ≤ 6 and PSA (ng/ml) ≤ 10), provided they were treated in a curative way (surgery or radiotherapy, without any chemotherapy)

5. Superior vena cava (SVC) syndrome persisting after SVC stenting

6. Thoracic radiotherapy needed at initiation of tumor treatment, except bone palliative radiotherapy on a painful or compressive metastasis, respecting 4 weeks delay between the end of radiotherapy and the beginning of induction immunotherapy treatment

7. Symptomatic untreated brain metastasis (without previous whole brain radiotherapy or stereotactic ablative brain radiotherapy or without surgical resection). At least 4 weeks delay between the end of radiotherapy and the beginning of induction immunotherapy treatment should be respected. Asymptomatic brain metastasis, not needing corticosteroids greater than 10 mg prednisone equivalent daily or mannitol infusions, with no evolution on brain MRI or CT-scan within the previous month are allowed.

8. History of previous primary immunodeficiency, organ transplantation needing an immunosuppressive treatment, any immunosuppressive drug within 28 days before randomization date, or history of severe toxicity (grade 3/4) by immune mechanism linked to another immunotherapy treatment.

9. Systemic treatment with corticosteroids with greater dose than 10 mg prednisone equivalent daily, within 14 days before initiation of the immunotherapy induction. Inhaled, nasal or topic corticosteroids are allowed.

10. History of active autoimmune disease including rheumatoid polyarthritis, Lupus, Wegener disease. Patients with type I diabetes, or hypothyroidism, or immune cutaneous disease (vitiligo, psoriasis, alopecia) not needing any immunosuppressive systemic treatment, are allowed to be included.

11. Active inflammatory intestinal disease (diverticulosis, Crohn disease, Hemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhea

12. Active uncontrolled infection including tuberculosis, known acute viral hepatitis B and C according to serological tests. Patients with serological sequelae of cured viral hepatitis are allowed to be included.

13. HIV known infection

14. Living attenuated vaccine received within the 30 previous days

15. Previous treatment with anti-PD-1, anti-PD-L1 or Anti-CTLA4 antibody

16. Previous treatment with chemotherapy

17. General serious condition such as congestive uncontrolled cardiac failure, uncontrolled cardiac arrythmia, uncontrolled ischemic cardiac disease (unstable angina or history of myocardial infarction in the previous 6 months), history or stroke within the 6 previous months

18. Pre-existing lung interstitial disease as assessed by the diagnosis CT-scan.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Intergroupe Francophone de Cancerologie Thoracique

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Amiens - CHU

Amiens, , France

Angers - CHU

Angers, , France

Annecy - CH

Annecy, , France

Argenteuil -CH

Argenteuil, , France

Avignon - CH

Avignon, , France

Bordeaux - Polyclinique Nord

Bordeaux, , France

Boulogne - Ambroise Paré

Boulogne-Billancourt, , France

Caen - CHU Côte de Nacre

Caen, , France

Cahors - CH

Cahors, , France

CH de Pontoise

Cergy-Pontoise, , France

CH Chambery

Chambéry, , France

CH de Chauny

Chauny, , France

CH

Cholet, , France

Clamart - Hôpital Percy

Clamart, , France

Clermont Ferrand - CHU

Clermont-Ferrand, , France

Colmar - CH

Colmar, , France

Dijon - CAC

Dijon, , France

CHRU Grenoble

Grenoble, , France

La Roche Sur Yon - CH

La Roche-sur-Yon, , France

Centre Hospitalier - Pneumologie

Le Mans, , France

CHRU de Lille

Lille, , France

CHU de Limoges

Limoges, , France

CH Lyon Sud - Pneumologie

Lyon, , France

Institut Paoli Calmette

Marseille, , France

Marseille - Hôpital Européen

Marseille, , France

Mont de Marsan - CH

Mont-de-Marsan, , France

Mulhouse - CH

Mulhouse, , France

Nantes - Centre René Gauducheau

Nantes, , France

Centre Antoine Lacassagne

Nice, , France

CHU Nîmes

Nîmes, , France

Orléans - CH

Orléans, , France

AP-HP Hopital Tenon - Pneumologie

Paris, , France

AP-HP Hôpital Bichat

Paris, , France

GH Paris Saint-Joseph

Paris, , France

Hôpital Saint Louis APHP

Paris, , France

Paris - Institut Curie

Paris, , France

Rouen - CHU

Rouen, , France

Centre René Huguenin

Saint-Cloud, , France

HIA Begin

Saint-Mandé, , France

ICL Lucien Neuwirth

Saint-Priest-en-Jarez, , France

Saint Quentin - CH

Saint-Quentin, , France

Suresnes - Hopital Foch

Suresnes, , France

Toulon - CHI

Toulon, , France

CHU Toulouse

Toulouse, , France

CHRU de Tours

Tours, , France

Versailles - CH

Versailles, , France

CH de Villefranche - Pneumologie

Villefranche, , France

Countries

France

Related Links

https://www.ifct.fr/etudes-cliniques/151-ifct-1701

IFCT website

Other Identifiers

2017-002540-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IFCT-1701

Identifier Type: -

Identifier Source: org_study_id