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

NCT07418931 | Not Yet Recruiting Phase 2

• 1 other identifier: GOIRC-04-2024
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 15

Brief Summary

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

Conditions

Advanced Squamous Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is the Overall Survival (OS)

  The OS will be measured from the date of registration to the date of death by any cause and will be analyzed as survival rate at 1 year.

  Four years

Secondary Outcomes (9)

• Secondary outcomes

  Four years

• Secondary Outcome

  Three and five years

• Secondary Outcome

  Four years

• Secondary Outcome

  Four years

• Secondary Outcome

  Four years

Study Arms (3)

CDA activity < 7.2 U/mg

EXPERIMENTAL

Patients with low CDA activity (\< 7.2 U/mg) will receive: Cisplatin 80 mg/sqm on day 1 + Gemcitabine 1200 mg/sqm on days 1 and 8 and Cemiplimab 350 mg on day 1 administered every 3 weeks for 4 cycles followed by Cemiplimab 350 mg every 3 weeks until disease progression or unacceptable toxicity or a maximum of 108 weeks

Drug: Cemiplimab 350 mg IV; Drug: Cisplatin 80 mg/sqm IV; Drug: Gemcitabine 1200 mg/sqm b

CDA activity ≥ 7.2 U/mg

EXPERIMENTAL

Patients with high CDA activity (≥ 7.2 U/mg) will receive carboplatin at an area under the concentration-time curve of 6 mg/mL/min IV (day 1) + paclitaxel 200 mg/sqm on days 1 and Cemiplimab 350 mg on day 1 administered every 21 days for 4 cycles followed by Cemiplimab 350 mg every 3 weeks until disease progression or unacceptable toxicity or a maximum of 108 weeks

Drug: Cemiplimab 350 mg IV; Drug: Paclitaxel 200 mg/sqm IV; Drug: Carboplatin AUC 6 IVb

CDA activity < 7.2 U/mg (at investigator's choice)

EXPERIMENTAL

At Investigator's choice: Carboplatin AUC 5 day 1 + Gemcitabine 1000 mg/sqm on days 1 and 8 every 21 days for 4 cycles plus Cemiplimab 350 mg every 3 weeks followed by Cemiplimab 350 mg every 3 weeks until disease progression or unacceptable toxicity or a maximum of 108 weeks

Drug: Cemiplimab 350 mg IV; Drug: Carboplatin AUC 5 IVa; Drug: Gemcitabine 1000 mg/sqm a

Interventions

Cemiplimab 350 mg IV DRUG

Over approximately 30 min +/- 10 min. Day 1 every 21 days

CDA activity < 7.2 U/mg; CDA activity < 7.2 U/mg (at investigator's choice); CDA activity ≥ 7.2 U/mg

Paclitaxel 200 mg/sqm IV DRUG

Over approximately 180 min. Day 1 every 21 days

CDA activity ≥ 7.2 U/mg

Carboplatin AUC 5 IVa DRUG

Over approximately 15-30 min. Day 1 every 21 days

CDA activity < 7.2 U/mg (at investigator's choice)

Cisplatin 80 mg/sqm IV DRUG

Over approximately 20 min. Day 1 every 21 days

CDA activity < 7.2 U/mg

Gemcitabine 1000 mg/sqm a DRUG

Over approximately 30 min. Day 1 and 8 every 21 days

CDA activity < 7.2 U/mg (at investigator's choice)

Carboplatin AUC 6 IVb DRUG

Over approximately 15-30 min. Day 1 every 21 days

CDA activity ≥ 7.2 U/mg

Gemcitabine 1200 mg/sqm b DRUG

Over approximately 30 min. Day 1 and 8 every 21 days

CDA activity < 7.2 U/mg

Eligibility Criteria

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

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.

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.

Sponsors & Collaborators

• Gruppo Oncologico Italiano di Ricerca Clinica: lead

Study Sites (15)

UOC Oncologia Medica IRCCS Azienda Ospedaliero-Universitaria Policlinico Sant'Orsola

Bologna, BO, 40138, Italy

Location

SC Oncologia Azienda Ospedaliera Santa Croce e Carle di Cuneo

Cuneo, CN, 12100, Italy

Location

SSD Gruppo di Patologia Toracica IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l.

Meldola, FC, 47014, Italy

Location

UO Oncologia Clinica Azienda Ospedaliero-Universitaria di Ferrara, Arcispedale Sant' Anna

Cona, FE, 44124, Italy

Location

UOC Oncologia Medica Ospedale Versilia

Lido di Camaiore, LU, 55041, Italy

Location

UOC Oncologia Medica Ospedale San Luca

Lucca, LU, 55100, Italy

Location

SC Oncologia Medica Ospedale Carlo Poma, ASST Mantova

Mantova, MN, 46100, Italy

Location

SOD Oncopneumologia Azienda Ospedaliero Universitaria Pisana

Pisa, PI, 56124, Italy

Location

SOC Oncologia Medica Nuovo Ospedale Santo Stefano

Prato, PO, 59100, Italy

Location

UOC Oncologia Medica Azienda Ospedaliero-Universitaria di Parma

Parma, PR, 43126, Italy

Location

SC Oncologia Medica Provinciale Azienda USL IRCCS di Reggio Emilia

Reggio Emilia, RE, 42123, Italy

Location

UOC Oncologia Medica Ospedale dell'Alta Val d'Elsa

Poggibonsi, SI, 53036, Italy

Location

UOC di Oncologia Medica Azienda Ospedaliero Universitaria di Sassari Ospedale Civile SS. Annunziata

Sassari, SS, 07100, Italy

Location

SC di Oncologia Azienda Ospedaliera Santa Maria

Terni, TR, 05100, Italy

Location

UOC Oncologia Medica ASST Valle Olona - Ospedale di Saronno

Saronno, VA, 21047, Italy

Location

MeSH Terms

Interventions

cemiplimab; Paclitaxel; Cisplatin; Gemcitabine

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Carmelo Tibaldi, MD

CONTACT

+39 0583 055748; carmelo.tibaldi@uslnordovest.toscana.it

Study Design

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

Study Record Dates

• First Submitted: February 4, 2026
• First Posted: February 18, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): November 1, 2030
• Last Updated: February 18, 2026

Record last verified: 2026-01

Locations

IT (15)