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Brief Title: An Open-label, Randomized, Parallel, Non Comparative, Phase II Trial of Nivolumab Plus Ipilimumab Versus Platinum-based Chemotherapy Plus Nivolumab in Chemonaive Metastatic or Recurrent Squamous-Cell Lung Cancer (SqLC)
Official Title: SQUINT (Squamous Immunotherapy Nivolumab-Ipilimumab Trial): An Open-label, Randomized, Parallel, Non Comparative, Phase II Trial of Nivolumab Plus Ipilimumab Versus Platinum-based Chemotherapy Plus Nivolumab in Chemonaive Metastatic or Recurrent Squamous-Cell Lung Cancer (SqLC)
Study ID: NCT03823625
Brief Summary: Non-small-cell Lung Cancer (NSCLC) remains the leading cause of cancer death in Western Countries. Approximately 85% of lung cancers are of the non-small-cell type (NSCLC), with 25-30% of NSCLC being squamous histology type. Unlike nonsquamous NSCLC, squamous NSCLC rarely harbors epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations for which there are directed therapies, and until the recent approval of immunotherapies for pretreated squamous NSCLC, a limited number of traditional cytotoxic chemotherapy drugs have been FDA-approved for use in the treatment of advanced and metastatic squamous NSCLC. A platinum-based combination chemotherapy regimen has been the standard first-line treatment for all NSCLC. Carboplatin is frequently substituted for cisplatin for patients who have poor renal function or who experience toxicities from cisplatin (most notably, nausea and vomiting). Taxanes, especially paclitaxel, or vinorelbine or gemcitabine, commonly complete the standard two-drug backbone of platinum-based chemotherapy for the first-line treatment of NSCLC, with platin-gemcitabine as the most commonly used regimen in Europe in patients with squamous-histology. A recent press release announced that pembrolizumab plus chemotherapy produced higher response rate when compared to chemotherapy alone in patients with squamous-cell lung cancer. Nevertheless, no data on Progression-Free Survival (PFS) and Overall Survival (OS) are available. Therefore, considering the lack of data in patients with squamous histology and the lack of information about efficacy of combinations of immune-checkpoints inhibitors versus immune-checkpoint inhibitor plus chemotherapy, there is a strong rationale for conducting a study assessing efficacy of such strategies in patients with advanced, metastatic squamous-cell lung cancer.
Detailed Description: Better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 (PD-1) and its ligand (PD-L1), on T cells, has led to high activity in cancer patients with long lasting responses. In the KEYNOTE 024 the anti-PD-1 inhibitor Pembrolizumab significantly prolonged progression-free survival (PFS) and overall survival (OS) of patients with advanced NSCLC and high PD-L1 level (\>50% of tumor cells) compared to platinum based chemotherapy, thus becoming a new standard of care in front line setting. However, the trial was not restricted to squamous population, with approximately 18% per arm having this histology. Nivolumab, another PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial comparing the drug to docetaxel, in second-line setting. Importantly, the benefit produced by the drug was irrespective of PD-L1 expression suggesting that the high mutation burden of squamous-cell lung carcinoma is more relevant than the expression of a single biomarker, at least in pretreated individuals. In addition, recent studies in chemo naive patients with non-squamous histology demonstrated that combination of chemotherapy and immunotherapy is superior to chemotherapy alone in terms of Overall Survival irrespective of PD-L1 expression (Keynote 189 and IMPOWER 150). In addition, the CheckMate 227 study recently showed that, in chemonaive NSCLC, combination of nivolumab and ipilimumab was superior to chemotherapy alone in patients with high tumor mutational burden (TMB), irrespective of PD-L1 expression. A recent press release announced that pembrolizumab plus chemotherapy produced higher response rate when compared to chemotherapy alone in patients with squamous-cell lung cancer (Keynote 407). Nevertheless, no data on Progression-Free Survival and Overall Survival are available. Therefore, considering the lack of data in patients with squamous histology and the lack of information about efficacy of combinations of immune-checkpoints inhibitors versus immune-checkpoint inhibitor plus chemotherapy, there is a strong rationale for conducting a study assessing efficacy of such strategies in patients with advanced, metastatic squamous-cell lung cancer.
Minimum Age: 18 Years
Eligible Ages: ADULT, OLDER_ADULT
Sex: ALL
Healthy Volunteers: No
IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica, Meldola, Forlì- Cesena, Italy
Ospedale "Infermi" Rimini, Rimini, Italia, Italy
Centro di Riferimento Oncologico della Basilicata, Rionero In Vulture, Potenza, Italy
Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica, Negrar, Verona, Italy
Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8, Arezzo, , Italy
IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari, Genova, , Italy
Istituto Europeo di Oncologia - Divisione di Oncologia Toracica, Milano, , Italy
A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio, Modena, , Italy
A.O.R.N dei Colli - Ospedale Monaldi, Napoli, , Italy
I.R.C.C.S. Istituto Oncologico Veneto, Padova, , Italy
Azienda Ospedaliera Universitaria Paolo Giaccone, Palermo, , Italy
Casa di Cura La Maddalena- U.O. Oncologia medica, Palermo, , Italy
Azienda Ospedaliera di Perugia- S.C. Oncologia Medica, Perugia, , Italy
Ospedale di Ravenna- Oncologia Medica, Ravenna, , Italy
IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, , Italy
Azienda Ospedaliera San Camillo-Forlanini, Roma, , Italy
Policlinico Universitario "Campus Biomedico" di Roma, Roma, , Italy
Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica, Verona, , Italy
Name: Federico Cappuzzo
Affiliation: Ospedale di Ravenna
Role: PRINCIPAL_INVESTIGATOR