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Metastatic NSCLCPhase 2/3DIALNCT05255302

De-escalation Immunotherapy mAintenance Duration Trial for Stage IV Lung Cancer Patients With Disease Control After Chemo-immunotherapy Induction

A Phase 2/3 study testing Pembrolizumab before randomization, Chemotherapy and Pemetrexed in people with Metastatic NSCLC, run by Intergroupe Francophone de Cancerologie Thoracique at 44 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Immunotherapeutic approaches recently have demonstrated clinical efficacy in several cancer types, including melanoma and NSCLC. As a matter of fact, first registration trials of immune-checkpoints inhibitors (ICI) in second-line settings (pembrolizumab as well as nivolumab or atezolizumab) had stated that ICI could… Read more about this study

Who is it for?
Ages 18 to 74 years
Conditions the study is for
Metastatic NSCLC
What is being tested?
Pembrolizumab before randomization, Chemotherapy and Pemetrexed
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,360 participants
Where
44 sitesFrance
Study dates
2 May 2022to 1 Jun 2029
Phase
Phase 2/3
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 to 74 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Patients with histologically confirmed metastatic NSCLC (Stage IV accordingly to 8th classification TNM, UICC 2015). A cytologically-proven NSCLC is allowed if a cytoblock has been prepared.
  • PD-L1 tumor content as assessed locally by the investigator center.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
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  • Weight loss< 10% within 3 months of study entry.
  • 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
  • The Investigator must confirm prior to enrolment that the patient has adequate tumor tissue available. Tumor biopsy should be exploitable for molecular analysis. If archival tissue is either insufficient or unavailable, the patient may still be eligible upon discussion with IFCT.
  • Note: Tumor tissue collected after the patient was diagnosed with metastatic disease is preferred.
  • Tumor tissue sample must not be from locations previously radiated. Tumor sample must be 1 block or at least 7 unstained slides of analyzable tissue.
  • Adequate biological functions:
  • Creatinine Clearance ≥ 45 mL/min (Cockcroft or MDRD or CKD-epi); neutrophils≥ 1500/mm3 ; platelets ≥100 000/mm3 ; Hemoglobin≥ 9g/dL ; AST and ALT< 3x ULN, total bilirubin < 2xULN (patients with hepatic metastases or Gilbert's syndrome must have AST and ALT ≤ 5 x ULN and a baseline total bilirubin ≤ 2xULN).
  • 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) 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 6 months following the last dose.
  • Patient has national health insurance coverage.

Who cannot join

  • Small cell lung cancer or tumors with mixed histology including a SCLC component.
  • Note : Sarcomatoid histology is allowed. Neuro-endocrine large cell lung cancer with molecular features of small-cell lung cancer (i.e; Rb loss associated with TP53 mutation) will not be eligible. Other neuro-endocrine large cell subtypes, i.e. with adenocarcinoma features (STK11 or K-Ras mutations) will be eligible. In case of doubt, please contact the sponsor.
  • Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R ou L861X mutations in exon 21, G719A/S mutation in exon 18, exon 20 insertion) or HER2 exon 20 insertion (either tissue or plasma cfDNA mutation).
  • Known ALK, ROS1, Ret, NTRK, NRG1 gene rearrangement as assessed by immunohistochemistry, FISH or NGS (ADN or ARN) sequencing by local genetics and/or pathology laboratory.
  • Previous or active cancer within the previous 3 years (except for treated carcinoma in situ of the cervix, or basal cell skin cancer treated or not). Patients with a prostate adenocarcinoma history within the previous 3 years could be included in case of localized prostate cancer, with good prognostic factors according to d'Amico classification (≤T2a, score de Gleason ≤ 6 and PSA ≤ 10 (ng/ml)) provided they were treated in a curative way (surgery or radiotherapy, without any chemotherapy).
  • Superior vena cava syndrome persisting despite VCS stenting.
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  • Radiotherapy needed at initiation of tumour treatment, except bone palliative radiotherapy on a painful or compressive metastasis, respecting 1 week delay between the end of radiotherapy and the beginning of treatment
  • Symptomatic untreated brain metastasis (without previous whole brain radiotherapy or stereotactic ablative brain radiotherapy or without surgical resection). At least 2 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, 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 but not limited to rheumatoid polyarthritis, myasthenia, autoimmune hepatitis, systemic Lupus, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome with interstitial pulmonary disease, recent Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
  • Patients with type I diabetes, or hypothyroidism, or immune cutaneous disease (vitiligo, psoriasis, alopecia) or benign rheumatoid polyarthritis not needing any immunosuppressive systemic treatment, or benign sicca syndrome (Sjogren) without interstitial pulmonary disease, or history of past Guillain-Barre syndrome, totally reversible with no sequelae, no systemic immunosuppressive treatment during the last 20 years, are allowed to be included.
  • Active inflammatory intestinal disease (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. Past primary pulmonary tuberculosis in youth does not consist of a contra-indication. Past tuberculosis disease history does not consist of a contra-indication provided the patient was treated during at least 6 months by anti-tuberculosis antibiotic treatment.
  • Known HIV infection
  • Living attenuated vaccine received within the 30 previous days
  • Previous treatment with anti-PD-1, anti-PD-L1, Anti-CTLA4 or any ICI antibody
  • Previous treatment with chemotherapy for lung cancer. However, if a patient has a lung adenocarcinoma, previous cisplatin treatment for another cancer type with squamous histology (Head and Neck, bladder) may be allowed provided the sponsor accepts, and provided blood tests are normal (see above).
  • General serious condition such as congestive uncontrolled cardiac failure, uncontrolled cardiac arrythmia, uncontrolled ischemic cardiac disease (unstable angina or history of myocardial infarction within the previous 6 months), history or stroke within the 6 previous months. Patients with a significant cardiac history, even if controlled, should have a LVEF > 50%.
  • Pre-existing moderate or severe lung interstitial disease as assessed by the diagnosis CT-scan.
  • Inability to comply with study and/or follow-up procedures for family, social, geographic or psychological reasons.
  • Pregnant, lactating, or breastfeeding women.
  • Patients deprived of liberty by judicial or administrative decision
  • Patient who is subject to legal protection or who is unable to express his will

Trial locations and contacts

44 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Clinical Operations Manager contact

0156811046 ext. 33

contact@ifct.fr

44 sites in 1 country

France44 sites, 41 recruiting

  • Aix-en-Provence - CH

    Aix-en-Provence

    Stéphanie MARTINEZ, Dr, contact@ifct.fr

    Not yet recruiting

  • Amiens - Clinique de l'Europe

    Amiens

    Charles DAYEN, Dr

    Not yet recruiting

  • Angers - CHU

    Angers

    Youssef OULKHOUIR, Dr, contact@ifct.fr

    Not yet recruiting

  • Avignon - CH

    Avignon

    Nicolas CLOAREC, Dr, contact@ifct.fr

    Not yet recruiting

  • Besançon - CHU

    Besançon

    Virginie WESTEEL, contact@ifct.fr

    Not yet recruiting

  • Bordeaux - Polyclinique

    Bordeaux

    Sigolène GALLAND - GIRODET, Dr, contact@ifct.fr

    Not yet recruiting

  • CHU de Bordeaux

    Bordeaux

    Charlotte DOMBLIDES, MD, contact@ifct.fr

    Not yet recruiting

  • Caen - CHU Côte de Nacre

    Caen, 14000

    Jeannick MADELAINE, Dr, contact@ifct.fr

    Recruiting

  • Cannes - CH

    Cannes

    Yannick DUVAL, contact@ifct.fr

    Not yet recruiting

  • Chauny - Centre Hospitalier

    Chauny

    Patrick DUMONT, MD, contact@ifct.fr

    Not yet recruiting

  • CH

    Colmar

    Lionel MOREAU, contact@ifct.fr

    Not yet recruiting

  • Centre Georges François Leclerc

    Dijon

    Cléa FRAISSE, Dr, contact@ifct.fr

    Not yet recruiting

  • CHRU Grenoble

    Grenoble

    Active, not recruiting

  • La Roche Sur Yon - CH

    La Roche-sur-Yon, 85925

    Cyril GUIBERT, Dr

    Not yet recruiting

  • CH de Versailles

    Le Chesnay

    Cécile DUJON, Dr, contact@ifct.fr

    Not yet recruiting

  • Centre Hospitalier - Pneumologie

    Le Mans, 72000

    Camille GUGUEN, Dr, contact@ifct.fr

    Not yet recruiting

  • CHRU de Lille

    Lille

    Alexis CORTOT, Pr, contact@ifct.fr

    Not yet recruiting

  • CHU de Limoges

    Limoges

    Thomas EGENOD, Dr, contact@ifct.fr

    Not yet recruiting

  • Lyon - Hôpital Jean Mermoz

    Lyon

    Pierre BOMBARON, MD

    Not yet recruiting

  • Marseille - Hôpital Européen

    Marseille

    Jacques LE TREUT, Dr, contact@ifct.fr

    Not yet recruiting

  • Meaux - CH

    Meaux

    Chrystèle LOCHER, Dr, contact@ifct.fr

    Not yet recruiting

  • Metz - Hôpital Robert Schuman

    Metz

    Active, not recruiting

  • Hôpital Arnaud de Villeneuve

    Montpellier, 34295

    Benoit ROCH, Dr

    Not yet recruiting

  • Centre Hospitalier

    Mulhouse, 68070

    Didier DEBIEUVRE, Dr

    Not yet recruiting

  • Nantes - CHU Hôpital Laënnec

    Nantes

    Elvire PONS-TOSTIVINT, Dr, contact@ifct.fr

    Not yet recruiting

  • Nice - CRLCC

    Nice

    Josiane OTTO, Dr, contact@ifct.fr

    Not yet recruiting

  • Orléans - CHR

    Orléans

    Hugues MOREL, Dr, contact@ifct.fr

    Not yet recruiting

  • Paris - APHP - Hopital Tenon

    Paris, 75020

    Active, not recruiting

  • Institut CURIE

    Paris, 75248

    Sophie BEAUCAIRE DANEL, Dr

    Not yet recruiting

  • Hôpital Bichat - Claude - Bernard

    Paris

    Gérard ZALCMAN, Pr, contact@ifct.fr

    Recruiting

  • Reims - CHU

    Reims

    Maxime DEWOLF, Dr, contact@ifct.fr

    Not yet recruiting

  • Rouen - CHU

    Rouen

    Florian GUISIER, Dr, contact@ifct.fr

    Not yet recruiting

  • Centre René Huguenin

    Saint-Cloud, 92210

    Sophie BEAUCAIRE DANEL, Dr

    Not yet recruiting

  • CHU Saint-Etienne Pneumologie

    Saint-Etienne, 42000

    Pierre Fournel, Dr, contact@ifct.fr

    Franck Morin, +33.1.56.81.10.45, franck.morin@ifct.asso.fr

    Not yet recruiting

  • Hôpital privé de la Loire

    Saint-Etienne

    Claire TISSOT, Dr, contact@ifct.fr

    Not yet recruiting

  • Institut de Cancérologie de l'Ouest - René Gauducheau

    Saint-Herblain, 44805

    Sandrine Hiret, Dr, contact@ifct.fr

    Not yet recruiting

  • Saint-Nazaire - Clinique Mutualiste de l'Estuaire

    Saint-Nazaire

    Thierry CHATELLIER, MD, contact@ifct.fr

    Not yet recruiting

  • CHU de La Réunion-Site Sud

    Saint-Pierre, 97448

    Eric Huchot, Dr, contact@ifct.fr

    Not yet recruiting

  • Centre Hospitalier

    Saint-Quentin, 02100

    Charles DAYEN, Dr

    Not yet recruiting

  • Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg

    Strasbourg, 67091

    Céline MASCAUX, Pr, contact@ifct.fr

    Not yet recruiting

  • Centre Hospitalier Intercommunal

    Toulon

    Clarisse AUDIGIER-VALETTE, Dr

    Not yet recruiting

  • Hôpital Larrey (CHU)

    Toulouse, 31059

    Laurence BIGAY-GAME, Dr

    Not yet recruiting

  • CHRU de Tours

    Tours

    Eric PICHON, Dr, contact@ifct.fr

    Not yet recruiting

  • Centre Alexis Vautrin

    Vandœuvre-lès-Nancy, 54511

    Christelle CLEMENT-DUCHENE, Dr

    Not yet recruiting

Other trials in France

About this study

Official title: A Phase II-III Randomized Trial Evaluating Maintenance Pembrolizumab (± Pemetrexed) Until Progression Versus Observation (± Pemetrexed) After 6 Months of Platinum-based Doublet Chemotherapy Plus Pembrolizumab Induction Treatment in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)

Immunotherapeutic approaches recently have demonstrated clinical efficacy in several cancer types, including melanoma and NSCLC. As a matter of fact, first registration trials of immune-checkpoints inhibitors (ICI) in second-line settings (pembrolizumab as well as nivolumab or atezolizumab) had stated that ICI could be continued until disease progression or not tolerable toxicity, up to 5 years. This is only for the first-line registration studies that the arbitrary maximal duration of treatment of 2 years was set up by the Companies sponsoring such trials.

The aim is to study a de-escalation scheme of treatment from 2 years of immunotherapy to 6 months (27-weeks), in patients with controlled disease.

Read the detailed description

This is a phase II-III randomized, open-labelled, multicentre study for NSCLC patients who are naive of treatment for advanced disease. Patients will be given first-line chemotherapy + pembrolizumab: platinum doublet for at least 3 cycles, either paclitaxel-carboplatin for patient with SCC or 3 cycles of pemetrexed-platinum salt followed by 2 cycles of pemetrexed and 6 cycles of pembrolizumab.

Only patients with disease control, confirmed at 6 months (27-weeks) without drug-related toxicity imposing treatment discontinuation will be randomized 1:1 either to continuation of pembrolizumab (± pemetrexed for non-SCC) until disease progression or unacceptable toxicity or 2 years, or observation (± pemetrexed for non-SCC).

Patients will be stratified by performance status (0 versus 1), histology (SCC versus non-SCC), PD-L1 (PD-L1 < 1% versus 49%≥PD-L1 ≥ 1% versus PD-L1>49%), sex and response at randomization (partial response versus stabilisation).

Being tested
Pembrolizumab before randomization, Chemotherapy, Pemetrexed, Pembrolizumab after randomization
Keywords
IFCT, DIAL, NSCLC, Immunotherapy duration
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.

  • Pembrolizumab before randomizationDrug

    Pembrolizumab 200 mg every 3 weeks before randomization

  • ChemotherapyDrug

    Platinum doublet - 4 cycles: either paclitaxel-carboplatin for patient with SCC or pemetrexed-platinum salt followed by 2 cycles of pemetrexed until reaching the 6 months time-point for randomization Carboplatin AUC 5 for non-squamous cell carcinoma and AUC6 for squamous cell carcinoma every 3 weeks or cisplatin 75 mg/m² every 3 weeks Pemetrexed 500 mg/m² every 3 weeks or paclitaxel 175 mg/m² every 3 weeks

  • PemetrexedDrug

    Maintenance pemetrexed after randomization Pemetrexed 500 mg/m² every 3 weeks

  • Pembrolizumab after randomizationDrug

    Pembrolizumab 200 mg every 3 weeks after randomization

Study groups in NCT05255302
Study groupRoleWhat they receive
Arm A : control ArmActive comparator6 months treatment by chemotherapy + pembrolizumab followed by pembrolizumab ± pemetrexed for patients with non-squamous cell carcinoma (SCC) until 2 years max
Receives: Drug: Pembrolizumab before randomization; Drug: Chemotherapy; Drug: Pemetrexed; Drug: Pembrolizumab after randomization
Arm B : experimental armExperimental6 months treatment by chemotherapy + pembrolizumab followed by pemetrexed for patients with non-SCC or observation for patients with SCC
Receives: Drug: Pembrolizumab before randomization; Drug: Chemotherapy; Drug: Pemetrexed

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase II: 18-month overall survival (OS)

    Rate of patients not dead 18 months after inclusion

    Measured: 18 months after inclusion

  2. Phase III: overall survival

    Time from date of inclusion to the date of death due to any cause

    Measured: about 24 months after randomization

Secondary outcomes (8)

  1. Incidence, nature, and severity of adverse events

    Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)

    Measured: about 24 months after randomization

  2. Time until definitive health related quality of life score deterioration

    The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30/LC13 questionnaire will be used to determine time until definitive HRQoL score deterioration.

    Measured: about 24 months after randomization

  3. Change from baseline of EuroQol Quality of Life 5-Dimension 5-Level Scale

    Change from baseline of EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) at all scheduled time points.

    Measured: about 24 months after randomization

  4. Progression-Free Survival (PFS)

    Time between the date of randomization and the first date of documented progression, as determined by investigator, or death due to any cause, whichever occurs first.

    Measured: about 24 months after randomization

  5. OS according to histological subtype

    Time from date of inclusion to the date of death due to any cause according to histological subtype.

    Measured: about 24 months after randomization

  6. PFS according to histological subtype

    Time between the date of randomization and the first date of documented progression, as determined by investigator, or death due to any cause, whichever occurs first according to histological subtype.

    Measured: about 24 months after randomization

  7. OS according to PDL1 tumor level

    Time from date of inclusion to the date of death due to any cause according to PDL1 tumor level.

    Measured: about 24 months after randomization

  8. PFS according to PDL1 tumor level

    Time between the date of randomization and the first date of documented progression, as determined by investigator, or death due to any cause, whichever occurs first according to PDL1 tumor level.

    Measured: about 24 months after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2022
  2. Study start2 May 2022
  3. Primary completionMay 2025 (estimated)
  4. Study completion1 Jun 2029 (estimated)

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,360 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05255302
Sponsor's protocol ID
IFCT-2103
Other IDs
2021-006044-27
Acronym
DIAL
Status last verified
Mar 2025
First submitted
14 Feb 2022
Last updated
1 Apr 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Pembrolizumab before randomization, Chemotherapy and Pemetrexed in people with Metastatic NSCLC, run by Intergroupe Francophone de Cancerologie Thoracique at 44 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 19 inclusion and 24 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: looking for participants now, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Contact Clinical Operations Manager (0156811046 ext. 33, contact@ifct.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase II: 18-month overall survival (OS) (time frame: 18 months after inclusion). The study lists 2 primary outcomes in all. 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 NCT05255302.

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 1 Apr 2025.

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