Trial comparing the continuation of nivolumab and ipilimumab (doublet immunotherapy) to observation after a first 6 months treatment by nivolumab - ipilimumab in patient with stage IV lung cancer

A randomized phase 3 trial comparing continuation Nivolumab-Ipilimumab doublet immunotherapy until progression versus observation in treatment-naive patients with PDL1-positive stage IV Non-Small Cell Lung Cancer (NSCLC) after Nivolumab-Ipilimumab induction treatment - DICIPLE : Double Immune Checkpoint Inhibitors in PD-L1-positive stage IV non-small Lung CancEr

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-002540-33-FR

Enrollment

1360

Registered

2017-12-19

Start date

2017-12-15

Completion date

Unknown

Last updated

2025-01-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

PD-L1 positive stage IV Non Small Cell Lung Cancer

Interventions

Trade Name: Yervoy Product Name: Ipilimumab Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: IPILIMUMAB Other descriptive name: ipilimumab Concentration unit: mg/ml mill

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Signed Written Informed Consent: IFCT-1701 DICIPLE (version 1.0 26/06/2017) Page 24 sur 85 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 =65 years) yes F.1.3.1 Number of subjects for this age range 136

Exclusion criteria

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 IH, 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 syndrome persisting after VCS 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 RMI 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 hypothyroïdy, 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

Design outcomes

Primary

Measure	Time frame
Main Objective: According to a non-inferiority design, the primary objective will be to observe not significantly different median 1st Progression-Free Survival (=PFS) from the date of randomization (thus in disease controlled patients) for the 'stop and go' arm B, as compared to the standard arm A with induction immunotherapy, followed by cisplatin-based chemotherapy at progression. The null hypothesis will be that PFS would be below 16 months, the alternative hypothesis will be that PFS in the stop and go arm B will not statistically differ from 20 months.;Secondary Objective: QOL by using EQ-5D and a visual analogic scale questionnaire scores and assessing Time Until Definitive Deterioration (TUDD). PFS-2 from the date of second-line chemotherapy initiation or from the date of resuming double immunotherapy to 2nd progression date; OS from the date of randomization or from the date of inclusion to the date of death or last vital status information will be assessed in both arms. O Centrally-assessed PD-L1 tumour expression prognostic and predictive value (with the treatment arm as interaction term) Locally-assessed PD-L1 tumour expression prognostic and predictive value (with the treatment arm as interaction term). Pharmaco-economics study assessing for micro-costing of the two tested therapeutic strategies. Safety and tolerance will be performed in all treated patients.;Primary end point(s): Progression Free Survival;Timepoint(s) of evaluation of this end point: time between the date of randomization and the first date of documented progression, as determined by BICR, or death due to any cause, whichever occurs first.	—

Measure

Time frame

Main Objective: According to a non-inferiority design, the primary objective will be to observe not significantly different median 1st Progression-Free Survival (=PFS) from the date of randomization (thus in disease controlled patients) for the 'stop and go' arm B, as compared to the standard arm A with induction immunotherapy, followed by cisplatin-based chemotherapy at progression. The null hypothesis will be that PFS would be below 16 months, the alternative hypothesis will be that PFS in the stop and go arm B will not statistically differ from 20 months.;Secondary Objective: QOL by using EQ-5D and a visual analogic scale questionnaire scores and assessing Time Until Definitive Deterioration (TUDD). PFS-2 from the date of second-line chemotherapy initiation or from the date of resuming double immunotherapy to 2nd progression date; OS from the date of randomization or from the date of inclusion to the date of death or last vital status information will be assessed in both arms. O Centrally-assessed PD-L1 tumour expression prognostic and predictive value (with the treatment arm as interaction term) Locally-assessed PD-L1 tumour expression prognostic and predictive value (with the treatment arm as interaction term). Pharmaco-economics study assessing for micro-costing of the two tested therapeutic strategies. Safety and tolerance will be performed in all treated patients.;Primary end point(s): Progression Free Survival;Timepoint(s) of evaluation of this end point: time between the date of randomization and the first date of documented progression, as determined by BICR, or death due to any cause, whichever occurs first.

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Secondary

Measure	Time frame
Secondary end point(s): - PFS2 - Quality of life : Time Until Definitive Deterioration (TUDD) - Overall Survival - Safety analyses;Timepoint(s) of evaluation of this end point: - time between the start date of the second line and the second date of documented progression, as determined by BICR, or death due to any cause, whichever occurs first. At 6 and 12 months. - time interval between randomization and the first occurrence of a decrease in QLQ-C30 score= 5 points without any further improvement in HRQoL score = 5 points or any further available HRQoL data. - At 6 months and 12 months -Frequency, management and resolution of AR during study treatment and until 100 days	—

Measure

Time frame

Secondary end point(s): - PFS2 - Quality of life : Time Until Definitive Deterioration (TUDD) - Overall Survival - Safety analyses;Timepoint(s) of evaluation of this end point: - time between the start date of the second line and the second date of documented progression, as determined by BICR, or death due to any cause, whichever occurs first. At 6 and 12 months. - time interval between randomization and the first occurrence of a decrease in QLQ-C30 score= 5 points without any further improvement in HRQoL score = 5 points or any further available HRQoL data. - At 6 months and 12 months -Frequency, management and resolution of AR during study treatment and until 100 days

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Countries

France

Contacts

Public ContactContact

IFCT

contact@ifct.fr

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026