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)

NCT03823625 | Unknown Phase 2 DMC

• 1 other identifier: SQUINT-FoRT 04
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 18

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.

Conditions

Squamous-Cell Lung Cancer

Keywords

SqLC

Outcome Measures

Primary Outcomes (1)

• Efficacy in terms of Overall Survival in subjects with Stage IIIB not amenable to radical treatment or Stage IV or recurrent squamous-cell lung carcinoma treated in the study

  Overall Survival rate at 12 months in Arm A and B

  12 months

Secondary Outcomes (2)

• Biomarkers analysis

  48 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  48 months

Study Arms (2)

ARM A: Nivolumab plus Ipilimumab

EXPERIMENTAL

Immunotherapy will be given up to disease progression, toxicity or patient refusal and in any case for up to 24 months. Platinum-based chemotherapy will be given up to 6 cycles.

Drug: Nivolumab plus Ipilimumab

ARM B: Platinum-based chemotherapy plus Nivolumab

EXPERIMENTAL

Platinum-based chemotherapy will be given up to 6 cycles. Immunotherapy will be given up to disease progression, toxicity or patient refusal and in any case for up to 24 months.

Drug: Platinum-based chemotherapy plus Nivolumab

Interventions

Nivolumab plus Ipilimumab DRUG

Nivolumab will be administered at the standard dose of 360 mg every 3 weeks. Ipilimumab will be administered at the dose of 1 mg/kg every 6 weeks.

ARM A: Nivolumab plus Ipilimumab

Platinum-based chemotherapy plus Nivolumab DRUG

Nivolumab will be administered at the standard dose of 360 mg every 3 weeks. Platinum-based chemotherapy will be chosen by the investigator among the following regimens: * Cisplatin 80 mg/mq iv day 1 and Gemcitabine 1250 mg/mq iv days 1 and 8 every 21 days; * Carboplatin AUC 5 iv day 1 and Gemcitabine 1000 mg/mq iv days 1 and 8 iv every 21 days; * Carboplatin AUC 6 iv day 1 and paclitaxel 200 mg/mq iv day 1 every 21 days.

ARM B: Platinum-based chemotherapy plus Nivolumab

Eligibility Criteria

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

You may qualify if:

• Male and female patients willing and able to give written informed consent;
• Histologically confirmed diagnosis of Stage IIIB-not amenable to radical treatment or Stage IV or recurrent squamous-cell lung carcinoma;
• Tumor p63 (or p40) positive and TTF1 negative;
• Availability of tumor tissue for PD-L1 expression analysis. One formalin-fixed paraffin embedded tumor tissue block or a minimum of 16 unstained tumor tissue sections are acceptable. The tumor tissue sample may be fresh or archival if obtained within 6 months prior to enrollment, and there can have been no systemic therapy (eg, adjuvant or neoadjuvant chemotherapy) given after the sample was obtained. Tissue must be a core needle biopsy, excisional or incisional biopsy. Fine needle biopsies or drainage of pleural effusions with cytospins are not considered adequate for biomarker review. Biopsies of bone lesions that do not have a soft tissue component or decalcified bone tumor samples are also not acceptable;
• Availability of PD-L1 status;
• Performance status 0-1 (ECOG);
• Patient compliance to trial procedures;
• Age ≥ 18 years;
• Written informed consent;
• Adequate BM function (ANC ≥ 1.5x109/L, Platelets ≥ 100x109/L, HgB \> 9g/dl);
• Adequate liver function (bilirubin \< G2, transaminases no more than 3xULN/\<5xULN in present of liver metastases);
• Normal level of alkaline phosphatase and creatinine;
• If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of approved contraceptive method \[intrauterine contraceptive device (IUD), birth control pills, or barrier device\] during and for twenty-three (23) weeks after end of treatment;
• If men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product;
• Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to treatment. Patients with symptomatic tumor lesions that may require palliative radiotherapy within 4 weeks of first treatment are strongly encouraged to receive palliative radiotherapy prior to treatment. Patients are eligible if CNS metastases are adequately treated and patients are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization;

You may not qualify if:

• No tumor tissue available;
• Tumor negative for p63 (or p40) or positive for TTF1;
• Previous chemotherapy for stage IV disease;
• Concomitant radiotherapy or chemotherapy;
• Untreated brain metastases;
• Diagnosis of any other malignancy during the last 2 years, except for in situ carcinoma of cervix uteri and cutaneous squamous cell carcinoma;
• Pregnancy or lactating;
• Other serious illness or medical condition potentially interfering with the study.
• Patients with an active, known or suspected autoimmune disease. Patients with type I diabetes mellitus; hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll;
• Patients with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease;
• Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection;
• Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

Sponsors & Collaborators

• Fondazione Ricerca Traslazionale: lead
• Clinical Research Technology S.r.l.: collaborator

Study Sites (18)

IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)- Oncologia Medica

Meldola, Forlì- Cesena, 47014, Italy

RECRUITING

Ospedale "Infermi" Rimini

Rimini, Italia, 47900, Italy

RECRUITING

Centro di Riferimento Oncologico della Basilicata

Rionero in Vulture, Potenza, 85028, Italy

NOT YET RECRUITING

Sacro Cuore- Don Calabria Hospital- U.O.C. Oncologia Medica

Negrar, Verona, 37024, Italy

RECRUITING

Istituto Toscano Tumori Ospedale San Donato- U.O.C. di Oncologia Medica Dipartimento di Oncologia USL-8

Arezzo, 52100, Italy

NOT YET RECRUITING

IRCCS A.O.U. San Martino- IST- Istituto Nazionale per la Ricerca sul Cancro- U.O.S. Tumori Polmonari

Genova, 16132, Italy

NOT YET RECRUITING

Istituto Europeo di Oncologia - Divisione di Oncologia Toracica

Milan, 20141, Italy

RECRUITING

A.O.U. Policlinico di Modena- Oncologia Ematologia e Malattie Apparato Respiratorio

Modena, 41124, Italy

RECRUITING

A.O.R.N dei Colli - Ospedale Monaldi

Napoli, 80131, Italy

ACTIVE NOT RECRUITING

I.R.C.C.S. Istituto Oncologico Veneto

Padua, 35128, Italy

RECRUITING

Azienda Ospedaliera Universitaria Paolo Giaccone

Palermo, 90127, Italy

ACTIVE NOT RECRUITING

Casa di Cura La Maddalena- U.O. Oncologia medica

Palermo, 90146, Italy

NOT YET RECRUITING

Azienda Ospedaliera di Perugia- S.C. Oncologia Medica

Perugia, 06132, Italy

RECRUITING

Ospedale di Ravenna- Oncologia Medica

Ravenna, 48121, Italy

RECRUITING

IRCCS Arcispedale Santa Maria Nuova

Reggio Emilia, 42123, Italy

RECRUITING

Azienda Ospedaliera San Camillo-Forlanini

Roma, 00152, Italy

ACTIVE NOT RECRUITING

Policlinico Universitario "Campus Biomedico" di Roma

Roma, 00152, Italy

NOT YET RECRUITING

Policlinico 'G.B.Rossi' Borgo Roma - A.O.U. Integrata (Giampaolo Tortora)- Oncologia Medica

Verona, 37134, Italy

ACTIVE NOT RECRUITING

Related Publications (1)

• Cappuzzo F, Ricciuti B, Delmonte A, Bonanno L, Wang X, Lye WK, Gortz A, Andrikou K, Dal Maso A, Minuti G, Papi M, Alessi JV, Di Federico A, Rodig S, Awad MM, Metro G, Attili I, Vitiello F, Pilotto S, Gori S, Rossi G, Buglioni S, Giannarelli D, Landi L. MAPK Pathway-Activating Alteration and Immunotherapy Efficacy in Squamous Cell Lung Carcinoma: Results from the Randomized, Prospective SQUINT Trial. Clin Cancer Res. 2025 Mar 17;31(6):1027-1036. doi: 10.1158/1078-0432.CCR-24-2077.

  PMID: 39836372 DERIVED

MeSH Terms

Interventions

Nivolumab; Ipilimumab; Platinum Compounds

Intervention Hierarchy (Ancestors)

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

Study Officials

• Federico Cappuzzo

  Ospedale di Ravenna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Federico Cappuzzo

CONTACT

0544285206; f.cappuzzo@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, randomized, phase II trial

Study Record Dates

• First Submitted: February 2, 2018
• First Posted: January 30, 2019
• Study Start: September 13, 2017
• Primary Completion: February 28, 2021
• Study Completion: February 28, 2021
• Last Updated: March 25, 2020

Record last verified: 2020-03

Locations

IT (18)