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 - CECYDE trial - GOIRC-04-2024

Overview

Sponsor-declared trial summary

Key facts

Sponsor

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-07-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Regeneron Pharmaceuticals

External identifiers

EU CT number

2024-517799-40-00

ClinicalTrials.gov

NCT07418931

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To explore the efficacy of the combination of platinum+gemcitabine+cemiplimab in treatment naïve patients with metastatic or recurrent squamous lung cancer and low baseline CDA activity.

Secondary objectives 4

1. To evaluate activity of the combination of platinum+gemcitabine+cemiplimab as first line treatment for patients with metastatic or recurrent squamous lung cancer and low baseline CDA activity.
2. To evaluate activity of the combination of carboplatin+paclitaxel+cemiplimab as first line treatment for patients with metastatic or recurrent squamous lung cancer and high baseline CDA activity.
3. To assess the safety and tolerability profile of the combination of platinum+gemcitabine+cemiplimab as first line treatment for patients with metastatic or recurrent squamous lung cancer and low baseline CDA activity
4. To assess the safety and tolerability profile of the combination of carboplatin+paclitaxel+cemiplimab as first line treatment for patients with metastatic or recurrent squamous lung cancer and high baseline CDA activity.

Conditions and MedDRA coding

Advanced squamous non-small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. 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
2. 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
3. No need for concomitant chest irradiation
4. ECOG performance status 0-1
5. Life expectancy ≥ 12 weeks
6. 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.
7. 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.
8. 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 involvement) • Serum creatinine ≤ 1.5 times the ULN or creatinine clearance ≥ 60 mL/min, calculated according to the standard Cockcroft and Gault formula.
9. 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.
10. - 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 • For female patients of childbearing potential, agreement (by patient and/or partner) to use a highly effective form of contraception that results in a low failure rate (< 1% per year) when used consistently and correctly, and to continue its use for 6 months after the last dose of chemotherapy or at least 4 months after the last dose of cemiplimab, whichever occurs last. Such methods include: combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, and vasectomized partner (on the understanding that this is the only one partner during the whole study duration). Female patients of childbearing potential should agree not to donate eggs (ova/oocytes) to others or to freeze or store eggs for reproductive purposes from the start of dosing until 6 months after discontinuation of the study treatment.
11. Male patients who are sexually active must be willing to use barrier contraceptives (i.e.; by use of condoms) during sex with all partners during treatment with chemotherapy and for at least 6 months after the last dose of chemotherapy or at least 4 months after the last dose of cemiplimab, whichever occurs last. Men must refrain from donating sperm from the start of dosing until 6 months after discontinuing study treatment.
12. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
13. Ability to comply with the study protocol, in the investigator's judgment
14. Age ≥ 18 years at the time of study entry.
15. Histologically or cytologically (cell blocks only; smears are not acceptable) documented pulmonary squamous carcinoma
16. Stage IV or recurrent disease according to the AJCC 8th edition Cancer Staging Manual
17. No prior chemotherapy or treatment with another systemic anti-cancer agent. for the metastatic disease
18. 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
19. 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

Exclusion criteria 35

1. 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
2. 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
3. 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 CECYDE trial - GOIRC-04-2024 v. 1.0 of 25 August 2025 Page 28 of 91 screening, initiate HBV antiviral therapy before study entry.
4. 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
5. 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.
6. Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication
7. 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.
8. 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.
9. Major surgery (including open biopsy) within 28 days prior to first dose of protocol therapy
10. Prior allogeneic stem cell or solid organ transplantation
11. 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
12. 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
13. Any concurrent chemotherapy, IP, 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.
14. Treatment with any other investigational agent within 30 days prior to starting study treatment, or concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
15. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra- indicates the use of an investigational drug or puts the patient at high risk for treatment- related complications.
16. Active or prior documented autoimmune or inflammatory disorders
17. History or active autoimmune neurologic paraneoplastic syndrome (e.g. non-infectious encephalitis, Lambert-Eaton syndrome etc.) or any other immune-mediated paraneoplastic syndrome. Patients with SIADH or ectopic ATCH production are allowed on the study.
18. Patient has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP. Receipt of COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study medication.
19. History of idiopathic pulmonary fibrosis, including pneumonitis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
20. Prior therapy for metastatic disease with any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent and anti-CTL-A4 agent.
21. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of study treatment
22. Any condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization
23. History of leptomeningeal disease
24. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
25. History of allergies or hypersensitivity to any study drugs or study drug components or excipients.
26. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria: a) Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. b) Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with carboplatin, paclitaxel, gemcitabine or cemiplimab may be included only after consultation with the Study Physician.
27. Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results
28. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 6 months after last chemotherapy dose at least 4 months after the last dose of cemiplimab, whichever occurs last.
29. Patients should not donate blood whilst on this study.
30. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.Patients with indwelling catheters (e.g., Pleura-Cath) are allowed.
31. Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected calcium > ULN).
32. 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-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.
33. Transient ischemic attack or stroke within 1 year
34. Active SARS- COV-2 infection.
35. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is Overall Survival (OS) that will be measured from the date of registration to the date of death by any cause and will be analyzed as 1-year survival rate in the low CDA activity cohort.

Secondary endpoints 10

1. Median OS that will be measured from the date of registration to the date of death by any cause.
2. Survival rate at 3 year and 5 years will be analysed.
3. Progression Free Survival (PFS) that will be measured from the date of registration to the date of disease progression, based on the Investigator's assessment according to standard RECIST 1.1 criteria, or death and reported as median PFS and 6-month and 12-month PFS.
4. Objective Response Rate (ORR) that will be defined as the sum of complete response (CR)+ partial response (PR), based on the Investigator's assessment according to standard RECIST 1.1 criteria. Patients with no tumor assessment after baseline will be classified as non-responders.
5. Median Duration of Response (DoR) that will be measured from the date of first radiological evidence PR or CR to the date of first evidence of PD, both based on the Investigator's assessment according to standard RECIST 1.1 criteria17. Patients with no tumor assessment after baseline will be classified as non-responders.
6. Time to tumor response (TTR) that will be defined as the time from the start of treatment to the first objective of tumor response
7. Disease control rate (DCR) that will be defined as the sum of complete response (CR)+ partial response (PR)+ stable disease (SD), based on the Investigator's assessment according to standard RECIST 1.1 criteria
8. OS, PFS and ORR will be analysed by PD-L1 levels: < 1%; 1-49%, ≥ 50%.
9. Toxicity that will be based mainly on the frequency and severity of adverse events (all grades and grade 3-4); severity will be measured according to NCI Common terminology Criteria Adverse Event (CTCAE), version 5.0. The worst severity grade adverse event will be considered for each patient.
10. The secondary endpoints will be analysed separately for the low and high CDA activity cohorts.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Sponsor organisation

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Address

Viale Antonio Gramsci 14

City

Parma

Postcode

43126

Country

Italy

Scientific contact point

Organisation

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Contact name

Coordinating Investigator

Public contact point

Organisation

G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

Contact name

Coordinating Investigator

Third parties 1

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications