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

NCT03469960 | Completed Phase 3 DMC

• 2 other identifiers: IFCT-17012017-002540-33
• Study Type: interventional
• Target: 265
• Locations: 1 country
• Sites: 47

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

Keywords

IFCT; DICIPLE; NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS1)

  Time between the date of randomization and the first date of documented progression, as determined by BICR (Blinded Independent Central Review), or death due to any cause, whichever occurs first.

  24 months after randomization of the last subject

Secondary Outcomes (9)

• Progression Free Survival (PFS2)

  24 months after randomization of the last subject

• Quality of life (QoL)

  24 months after randomization of the last subject

• Overall survival (OS)

  6, 12 and 18 months after randomization

• Biological correlative exploratory studies (PD-L1)

  6 months

• Biological correlative exploratory studies (PD-L1 H score)

  6 months

Study Arms (2)

Arm A : standard treatment

ACTIVE COMPARATOR

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

Drug: Ipilimumab; Drug: Nivolumab

Arm B : experimental arm

EXPERIMENTAL

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

Drug: Ipilimumab; Drug: Nivolumab

Interventions

Ipilimumab DRUG

Ipilimumab 1 mg/kg every 6 weeks

Arm A : standard treatment; Arm B : experimental arm

Nivolumab DRUG

Nivolumab 3 mg/kg every 2 weeks

Arm A : standard treatment; Arm B : experimental arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Histologically-proven NSCLC (squamous or non-squamous)
• Stage IV (M1, including M1a pleural involvement) disease (8th classification TNM, UICC 2015)
• ECOG PS \< 1
• Weight loss\< 10% in previous 3 months
• No prior systemic anticancer therapy (including EGFR or ALK inhibitors) given as primary therapy for advanced or metastatic disease.
• Age≥ 18 years, \<75 years
• Life expectancy \> 3 months
• Measurable tumor disease by CT or MRI per RECIST 1.1 criteria
• Available tumor samples for centralized PD-L1 immunohistochemistry analysis
• PD-L1 tumor content ≥ 1% and \< 50% tumor cells as assessed locally by the investigator center
• 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)

You may not qualify if:

• Small cell lung cancer or tumors with mixt histology including a SCLC component
• 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).
• Known ALK or ROS1 gene rearrangement as assessed by immunohistochemistry, FISH or NGS sequencing
• 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)
• Superior vena cava (SVC) syndrome persisting after SVC stenting
• 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
• 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.
• 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.
• 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.
• 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.
• Active inflammatory intestinal disease (diverticulosis, Crohn disease, Hemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhea
• 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.
• HIV known infection
• Living attenuated vaccine received within the 30 previous days
• Previous treatment with anti-PD-1, anti-PD-L1 or Anti-CTLA4 antibody

Sponsors & Collaborators

• Intergroupe Francophone de Cancerologie Thoracique: lead

Study Sites (47)

Amiens - CHU

Amiens, France

Location

Angers - CHU

Angers, 49000, France

Location

Annecy - CH

Annecy, 74374, France

Location

Argenteuil -CH

Argenteuil, 95100, France

Location

Avignon - CH

Avignon, France

Location

Bordeaux - Polyclinique Nord

Bordeaux, France

Location

Boulogne - Ambroise Paré

Boulogne-Billancourt, France

Location

Caen - CHU Côte de Nacre

Caen, 14000, France

Location

Cahors - CH

Cahors, 46000, France

Location

CH de Pontoise

Cergy-Pontoise, France

Location

CH Chambery

Chambéry, France

Location

CH de Chauny

Chauny, France

Location

CH

Cholet, France

Location

Clamart - Hôpital Percy

Clamart, 92140, France

Location

Clermont Ferrand - CHU

Clermont-Ferrand, 63000, France

Location

Colmar - CH

Colmar, 68000, France

Location

Dijon - CAC

Dijon, 21000, France

Location

CHRU Grenoble

Grenoble, France

Location

La Roche Sur Yon - CH

La Roche-sur-Yon, 85925, France

Location

Centre Hospitalier - Pneumologie

Le Mans, 72000, France

Location

CHRU de Lille

Lille, France

Location

CHU de Limoges

Limoges, France

Location

CH Lyon Sud - Pneumologie

Lyon, France

Location

Institut Paoli Calmette

Marseille, France

Location

Marseille - Hôpital Européen

Marseille, France

Location

Mont de Marsan - CH

Mont-de-Marsan, 40000, France

Location

Mulhouse - CH

Mulhouse, 68000, France

Location

Nantes - Centre René Gauducheau

Nantes, 44805, France

Location

Centre Antoine Lacassagne

Nice, France

Location

CHU Nîmes

Nîmes, France

Location

Orléans - CH

Orléans, 45000, France

Location

AP-HP Hopital Tenon - Pneumologie

Paris, 75020, France

Location

AP-HP Hôpital Bichat

Paris, France

Location

GH Paris Saint-Joseph

Paris, France

Location

Hôpital Saint Louis APHP

Paris, France

Location

Paris - Institut Curie

Paris, France

Location

Rouen - CHU

Rouen, 76000, France

Location

Centre René Huguenin

Saint-Cloud, France

Location

HIA Begin

Saint-Mandé, France

Location

ICL Lucien Neuwirth

Saint-Priest-en-Jarez, France

Location

Saint Quentin - CH

Saint-Quentin, 02100, France

Location

Suresnes - Hopital Foch

Suresnes, 92151, France

Location

Toulon - CHI

Toulon, 83000, France

Location

CHU Toulouse

Toulouse, France

Location

CHRU de Tours

Tours, France

Location

Versailles - CH

Versailles, 78157, France

Location

CH de Villefranche - Pneumologie

Villefranche, France

Location

Related Links

• IFCT website

MeSH Terms

Interventions

Ipilimumab; Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2018
• First Posted: March 19, 2018
• Study Start: May 2, 2018
• Primary Completion: November 8, 2023
• Study Completion: October 15, 2025
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

FR (47)