A Multicenter Open-label Phase II Study of Cemiplimab Plus Chemotherapy, Selected on the Basis of Baseline Cytidine Deaminase Activity, in Advanced Squamous Non-small Cell Lung Cancer

Starting soon · Phase 2

Conditions studied: Advanced Squamous Non-Small Cell Lung Cancer

In brief

This is a multicenter phase II study enrolling treatment- naïve patients with metastatic or recurrent squamous carcinoma of the lung

Key facts

Study ID

NCT07418931

Run by

Gruppo Oncologico Italiano di Ricerca Clinica

People needed

108

Starts

2026-05-01

Expected to finish

2030-11-01

Last updated by the study team

2026-02-18

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Age > 18 years at the time of study entry.
• Histologically or cytologically (cell blocks only; smears are not acceptable) documented pulmonary squamous carcinoma.
• Stage IV or recurrent disease according to the AJCC 8th edition Cancer Staging Manual.
• Body weight > 30 kg
• No prior chemotherapy or treatment with another systemic anti-cancer agent for the metastatic disease.
• Patients who have received prior neo-adjuvant, adjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment- free interval of at least 6 months from enrolment since the last chemotherapy or completion of chemoradiotherapy.
• Patients who received prior anti-PD-(L)1 as adjuvant or neoadjuvant therapy at stage 3B /3C disease will be allowed if have experienced a treatment-free interval of at least 6 months from enrolment since the last immunotherapy dose.
• Known PD-L1 tumor status as determined by an IHC assay performed by local laboratory on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening.
• No need for concomitant chest irradiation.
• ECOG perforance status 0-1.
• Life expectancy ≥12 weeks.
• At least one lesion measurable according to RECIST v 1.1 outside of the CNS, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis > 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
• Adequate hematologic function as evidenced by absolute neutrophil count (ANC) ≥1,500/μL, hemoglobin ≥ 9.0 g/dL (5.58 mmol/L), and platelet count ≥ 100,000/μl.
• Adequate hepatic and renal function:
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN).
• ALT (SGPT), AST (SGOT) ≤ 2.5 x institutional upper limit of normal (< 5 x ULN if the liver has tumor involvment).
• Serum creatinine ≤ 1.5 times the ULN or creatinine clearance ≥ 60 mL/min, calculated according to the standard Cockcroft and Gault formula.
• The patient has adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) (PTT/aPTT) < 1.5 x ULN.
• Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). If receiving warfarin, the patient must have an INR ≤ 3.0.
• Female patients must have a negative pregnancy test and not be breast feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
• Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments and with LH and FSH levels in the post- menopausal range for the institution.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation

You may not qualify if…

• Patients with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene, or with anaplastic lymphoma kinase (EML4-ALK) translocations or with ROS1 proto-oncogene receptor tyrosine kinase (ROS1) translocations. EGFR mutations, ALK and ROS1 translocations will be assessed in never- smoker patients
• Symptomatic brain metastases or spinal cord compression (CT or MRI of the head is required within 4 weeks prior to registration) requiring immediate radiotherapy for palliation. Patients with asymptomatic CNS lesions are eligible, provided that all of the following criteria are met:
• The patient has no history of intracranial haemorrhage, spinal cord haemorrhage or haemorrhagic intracranial lesions
• At least 14 days between the end of stereotactic radiotherapy or whole brain radiotherapy and initiation of study treatment, or at least 28 days between neurosurgical resection and initiation of study treatment
• The patient is on a dose of corticosteroids ≤ 10 mg of oral prednisone or equivalent; anticonvulsant therapy at a stable dose is permitted
• Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla or spinal cord)
• There is no evidence of interim progression between completion of CNS directed therapy (if administered) and initiation of study treatment.
• History of leptomeningeal disease.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. Patients with indwelling catheters (e.g., Pleura-Cath) are allowed.
• Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected calcium > ULN).
• History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI or acute coronary syndrome more than 12 months prior to study entry is allowed); cardiac arrythmias requiring anti-arrythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.
• Transient ischemic attack or stroke within 1 year
• Active SARS- COV-2 infection.
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C.
• Participants with HBsAg positive who have controlled infection (serum HBV DNA PCR that is below the limit of detection and receiving anti-viral therapy for hepatitis B) are eligible. Participants with controlled infections must undergo periodic monitoring of HBV DNA. Participants must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study medication.
• Participants with HBsAg negative but total HBcAb positive are permitted with the following requirements: If serum HBV DNA PCR is above the limit of detection at screening, initiate HBV antiviral therapy before study entry. If serum HBV DNA PCR is below the limit of detection, periodic monitoring of HBsAg must be performed.
• Participants who are HCV Ab+ who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are eligible.
• Known positive serology for HIV. Participants with known controlled HIV infection (undetectable viral load on HIV RNA PCR) and CD4 count above 350 either spontaneously or on a stable antiviral regimen are eligible. For these participants monitoring will be performed per local standards.
• Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication
• Significant traumatic injury or radiotherapy involving an extensive field within the last 4 weeks prior to first dose of study treatment or anticipation of the need for major surgery during study treatment. Palliative radiotherapy to a limited field is allowed if concluded at least 2 weeks prior enrolment.
• Other malignancies (previous or current), except for adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, localized prostate cancer surgically treated with curative intent or ductal carcinoma in situ treated surgically treated with curative intent or if previous malignancy was more than 5 years prior and there are no signs or symptoms of recurrence.
• Major surgery (including open biopsy) within 28 days prior to first dose of protocol therapy.
• Prior allogeneic stem cell or solid organ transplantation.
• Patients with any underlying medical condition that might be aggravated by treatment or which cannot be controlled i.e. patients with active serious infection, uncontrolled diabetes mellitus, pericardial effusion.
• Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment other than those in the present study. Concurrent use of hormonal therapy for non-cancer- related conditions (e.g., hormone replacement therapy) is acceptable.

Where it is running

• UOC Oncologia Medica IRCCS Azienda Ospedaliero-Universitaria Policlinico Sant'Orsola — Bologna, BO, Italy
• SC Oncologia Azienda Ospedaliera Santa Croce e Carle di Cuneo — Cuneo, CN, Italy
• SSD Gruppo di Patologia Toracica IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l. — Meldola, FC, Italy
• UO Oncologia Clinica Azienda Ospedaliero-Universitaria di Ferrara, Arcispedale Sant' Anna — Cona, FE, Italy
• UOC Oncologia Medica Ospedale Versilia — Lido di Camaiore, LU, Italy
• UOC Oncologia Medica Ospedale San Luca — Lucca, LU, Italy
• SC Oncologia Medica Ospedale Carlo Poma, ASST Mantova — Mantua, MN, Italy
• SOD Oncopneumologia Azienda Ospedaliero Universitaria Pisana — Pisa, PI, Italy
• SOC Oncologia Medica Nuovo Ospedale Santo Stefano — Prato, PO, Italy
• UOC Oncologia Medica Azienda Ospedaliero-Universitaria di Parma — Parma, PR, Italy
• SC Oncologia Medica Provinciale Azienda USL IRCCS di Reggio Emilia — Reggio Emilia, RE, Italy
• UOC Oncologia Medica Ospedale dell'Alta Val d'Elsa — Poggibonsi, SI, Italy
• UOC di Oncologia Medica Azienda Ospedaliero Universitaria di Sassari Ospedale Civile SS. Annunziata — Sassari, SS, Italy
• SC di Oncologia Azienda Ospedaliera Santa Maria — Terni, TR, Italy
• UOC Oncologia Medica ASST Valle Olona - Ospedale di Saronno — Saronno, VA, Italy

Full record on ClinicalTrials.gov

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