BMS CA209-73L: A Phase 3, Randomized, Open Label Study to Compare Nivolumab plus Concurrent Chemoradiotherapy (CCRT) followed by Nivolumab plus Ipilimumab or Nivolumab plus CCRT Followed by Nivolumab vs CCRT followed by Durvalumab in Previously Untreated, Locally Advanced Non-small Cell Lung Cancer
cancer du poumon non à petites cellules localement avancé n’ayant jamais été traité
nivolumab+radiochimiothérapie concomittante (RCTC), puis nivolumab+ipilimumab (ou nivolumab seul) VS RCTC, puis durvalumab
- cancer du poumon non à petites cellules localement avancé confirmé histologiquement
- stade IIIA, IIIB ou IIIC
- se prête à une radiochimiothérapie concomittante définitive
Département d'Oncologie - Service d'oncologie médicale
Rue du Bugnon 46
Primary objective :
Comparer l'efficacité du traitement nivolumab + radiochimiothérapie concomittante (RCTC) suivi par nivolumab + ipilimumab au traitement par radiochimiothérapie concomittante suivi par durvalumab chez des patients atteints d'un cancer du poumon non à petites cellules localement avancé non traité
Inclusion criteria :
- Males and females, ≥18 years of age
- ECOG performance status ≤1
- Locally advanced stage IIIA, IIIB, or IIIC (T1-2 N2-3 M0, T3 N1-3 M0, or T4 N0-3 M0) histologically-confirmed NSCLC that is amenable to definitive CCRT. Participants who are not planned for potential curative surgical resection are eligible.
- Newly diagnosed and treatment-naïve, with no prior local or systemic anticancer therapy given as primary therapy for locally advanced disease
- All participants must have tissue submitted to a central laboratory during screening
Exclusion criteria :
- Any condition including medical, emotional, psychiatric, or logistical that, in the opinion of the Investigator, would preclude the patient from adhering to the protocol or would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results (eg, a condition associated with diarrhea or acute diverticulitis)
- Active infection requiring systemic therapy within 14 days prior to randomization
- Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
- Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
- Participants with a condition requiring systemic treatment with either corticosteroids (> 10mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- Presence of pleural/pericardial effusion on CT scan and/or X-ray, unless it is not cytologically positive nor exudative via pleuracentesis. Effusions that are too small to be tapped safely are acceptable
- Participants with EGFR mutation regardless of mutation type are excluded. Non-squamous tumor with unknown EGFR mutation status must be tested for EGFR mutation (PCR based test should be used).
- Known ALK translocation and/or ROS1 rearrangement
- Clinical evidence of hearing loss
- ≥ Grade 2 peripheral neuropathy
- History of organ or tissue transplant that requires systemic use of immune suppressive agents
- Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at sites where mandated locally.
- Prior thoracic radiotherapy. However, other prior radiotherapy is allowed and must be completed at least 30 days prior to study treatment with residual toxicities resolved prior to study enrollment.
- Use of an investigational agent or an investigational device within 28 days before administration of first dose of study drug
- Participants who have received a live / attenuated vaccine within 30 days before first treatment
- Treatment with botanical preparations (eg, herbal supplements or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to randomization/treatment.
- Pancoast tumor or other situations with surgery as part of management plan.
- Radiation plan does not comply with any of the following: i) Mean lung dose <20 Gy and/or V20<35%, AND V5≤60% ii) Mean esophagus dose <34Gy iii) Mean heart dose <15Gy