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Squamous-Cell Lung CancerPhase 2SQUINTNCT03823625

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)

A Phase 2 study testing Nivolumab plus Ipilimumab and Platinum-based chemotherapy plus Nivolumab in people with Squamous-Cell Lung Cancer, run by Fondazione Ricerca Traslazionale at 18 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Squamous-Cell Lung Cancer
What is being tested?
Nivolumab plus Ipilimumab and Platinum-based chemotherapy plus Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
112 participants
Where
18 sitesItaly
Study dates
13 Sep 2017to 28 Feb 2021
Phase
Phase 2
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
  • Chemonaive patient. Adjuvant/neoadjuvant chemotherapy is allowed if therapy was completed at least 6 months before trial inclusion;
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  • 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;
  • Patients must be either off corticosteroids, or on a stable or decreasing dose of ≥10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization.

Who cannot join

  • No tumor tissue available;
  • Tumor negative for p63 (or p40) or positive for TTF1;
  • Previous chemotherapy for stage IV disease;
  • Adjuvant or neoadjuvant chemotherapy completed less than 6 months before trial inclusion; adjuvant or neoadjuvant immunotherapy is not allowed;
  • Concomitant radiotherapy or chemotherapy;
  • Untreated brain metastases;
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  • 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.
  • Nivolumab and ipilimumab specific exclusion
  • 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).

Trial locations and contacts

18 sites in 1 country.

Federico Cappuzzo contact

0544285206

f.cappuzzo@gmail.com

18 sites in 1 country

Italy18 sites, 14 recruiting

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

    Arezzo, 52100

    Sergio Bracarda, +39 0575255438, sergio.bracarda@usl8.toscana.it

    Not yet recruiting

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

    Genova, 16132

    Francesco Grossi, +39 0105600385, fg1965@libero.it

    Not yet recruiting

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

    Meldola, Forlì- Cesena, 47014

    Angelo Delmonte, MD, +39 0543739100, angelo.delmonte@irst.emr.it

    Angelo Delmonte, MD

    Recruiting

  • Istituto Europeo di Oncologia - Divisione di Oncologia Toracica

    Milan, 20141

    Filippo De Marinis, MD, +39 0257489482, Filippo.DeMarinis@ieo.it

    Filippo De Marinis, MD

    Recruiting

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

    Modena, 41124

    Fausto Barbieri, MD, +39 0594224385, barbieri.fausto@policlinico.mo.it

    Fausto Barbieri, MD

    Recruiting

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

    Naples, 80131

    Active, not recruiting

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

    Negrar, Verona, 37024

    Stefania Gori, MD, +39 0456013472, stefania.gori@sacrocuore.it

    Stefania Gori, MD

    Recruiting

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

    Padova, 35128

    Laura Bonanno, MD, +39 0498215553, laura.bonanno@ioveneto.it

    Laura Bonanno, MD

    Recruiting

  • Azienda Ospedaliera Universitaria Paolo Giaccone

    Palermo, 90127

    Active, not recruiting

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

    Palermo, 90146

    Vittorio Gebbia, +39 0916806111, vittorio.gebbia@tin.it

    Not yet recruiting

  • Azienda Ospedaliera di Perugia- S.C. Oncologia Medica

    Perugia, 06132

    Vincenzo Minotti, MD, 0755784099, vinminotti@yahoo.it

    Vincenzo Minotti, MD

    Recruiting

  • Ospedale di Ravenna- Oncologia Medica

    Ravenna, 48121

    Federico Cappuzzo, MD, +39 0544285247, f.cappuzzo@googlemail.com

    Federico Cappuzzo, MD

    Recruiting

  • IRCCS Arcispedale Santa Maria Nuova

    Reggio Emilia, 42123

    Francesca Zanelli, MD, +39 0522296602, zanelli.francesca@asmn.re.it

    Francesca Zanelli, MD

    Recruiting

  • Ospedale "Infermi" Rimini

    Rimini, Italia, 47900

    Maximilian Papi, MD, maximilian.papi@auslromagna.it

    0541705413

    Recruiting

  • Centro di Riferimento Oncologico della Basilicata

    Rionero in Vulture, Potenza, 85028

    Michele Aieta, +39 0972726429, michele.aieta@crob.it

    Not yet recruiting

  • Azienda Ospedaliera San Camillo-Forlanini

    Roma, 00152

    Active, not recruiting

  • Policlinico Universitario "Campus Biomedico" di Roma

    Roma, 00152

    Daniele Santini, + 39 06225411344, d.santini@unicampus.it

    Not yet recruiting

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

    Verona, 37134

    Active, not recruiting

Other trials in Italy

About this study

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)

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.

Read the 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.

Being tested
Nivolumab plus Ipilimumab, Platinum-based chemotherapy plus Nivolumab
Keywords
SqLC

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nivolumab plus IpilimumabDrug

    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.

  • Platinum-based chemotherapy plus NivolumabDrug

    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.
Study groups in NCT03823625
Study groupRoleWhat they receive
ARM A: Nivolumab plus IpilimumabExperimentalImmunotherapy 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.
Receives: Drug: Nivolumab plus Ipilimumab
ARM B: Platinum-based chemotherapy plus NivolumabExperimentalPlatinum-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.
Receives: Drug: Platinum-based chemotherapy plus Nivolumab

What is being measured

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

  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

    Measured: 12 months

Secondary outcomes (2)

  1. Biomarkers analysis

    Correlation of PD-L1 expression and/or TMB with outcome in Arm A and B

    Measured: 48 months

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

    Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Measured: 48 months

Timeline

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

  1. First posted30 Jan 2019
  2. Study start13 Sep 2017
  3. Primary completion28 Feb 2021 (estimated)
  4. Study completion28 Feb 2021 (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
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Open-label, randomized, phase II trial
Masking
None (open label)
Enrolment
112 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03823625
Sponsor's protocol ID
SQUINT-FoRT 04
Acronym
SQUINT
Status last verified
Mar 2020
First submitted
2 Feb 2018
Last updated
25 Mar 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 39836372

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab plus Ipilimumab and Platinum-based chemotherapy plus Nivolumab in people with Squamous-Cell Lung Cancer, run by Fondazione Ricerca Traslazionale at 18 sites in Italy.

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 17 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 25 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Italy. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Federico Cappuzzo (0544285206, f.cappuzzo@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 12 months). 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 NCT03823625, which also lists 1 linked publication.

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 25 Mar 2020.

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