NSCLC Stage IVPhase 2ICARSNCT06219317
Immunotherapy Consolidation After Radical Treatment of Synchronous Oligo-metastatic NSCLC
A Phase 2 study testing Cemiplimab in people with NSCLC Stage IV, run by European Organisation for Research and Treatment of Cancer - EORTC at 12 sites in 5 countries.
Trial summary
This is a multi-center, double-blind, placebo-controlled randomized phase II study to assess whether continuation of cemiplimab treatment (for up to 12 months) increases progression-free survival (PFS) as compared to placebo in patients with a stage IV, synchronous, oligometastatic non-small cell lung cancer (NSCLC)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC Stage IV
- What is being tested?
- Cemiplimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 136 participants
- Where
- 12 sitesin 5 countries
- Study dates
- 14 Jan 2025to Jan 2030
- Phase
- Phase 2
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
- Histologic or cytologic confirmation of NSCLC. If small-cell elements present, participant will be ineligible.
- Synchronous oligometastatic disease at diagnosis - and still oligometastatic at registration into the study - defined as maximum 5 metastases, in maximum 3 organs. Hilar, mediastinal and/or supraclavicular lymph nodes are not considered as metastases.
- Age at registration ≥18 years
- Eastern Cooperative Oncology Group performance status (ECOG PS)/ World Health Organization (WHO) 0-1.
- Hepatic function:
- Serum total bilirubin ≤1.5x upper limit of normal (ULN), or ≤3x ULN, if liver metastases or in patients with history of Gilbert syndrome
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- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤3x ULN (or ≤5x ULN, if liver metastases)
- Renal function:
- Glomerular filtration rate (GFR) based on the modification of diet in renal disease (MDRD) equation ≥30 mL/min
- Bone marrow function:
- Hemoglobin ≥9.0 g/dL
- Absolute neutrophil count (ANC) ≥1.5 x 109/L
- Platelet count ≥100 x 109/L
- Women of childbearing potential (WOCBP) must have a negative serum or highly sensitive urine pregnancy test within 7 days prior to the first dose of treatment.
- Note: Women of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrhoeic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression, or other reasons.
- Patients of childbearing / reproductive potential should agree to use adequate birth control measures, as defined by the protocol, during the study treatment period and for:
- At least 6 months after the last dose of pemetrexed-if pemetrexed was administered.
- At least 6 months after the last dose of cemiplimab/placebo. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. Such methods are detailed in Appendix Y.
- Women who are breast feeding should discontinue nursing prior to the first dose of study treatment and until:
- At least 6 months after the last dose of pemetrexed, if pemetrexed was administered.
- At least 6 months after the last dose of cemiplimab/placebo.
- 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.
- Stable disease, partial or complete response according to RECIST v.1.1 after 4 cycles of induction treatment and radical treatment of all residual disease (if applicable). Patients with progressive disease will be excluded.
- Anticipated life expectancy >12 weeks
- Hepatic function:
- Serum total bilirubin ≤1.5x ULN (or ≤3x ULN, if liver metastases or in patients with history of Gilbert syndrome)
- AST and/or ALT ≤3x ULN (or ≤5x ULN, if liver metastases)
- Renal function:
- GFR based on MDRD equation ≥30 mL/min
- Bone marrow function:
- Hemoglobin ≥9.0 g/dL
- ANC ≥1.5 x 109/L
- Platelet count ≥100 x 109/L
- WOCBP must have a negative serum or highly negative urine pregnancy test within 7 days prior to the first dose of consolidation treatment.
Who cannot join
- Presence of malignant pleural, pericardial and/or peritoneal effusion.
- Presence of leptomeningeal carcinomatosis.
- Tumour known to be positive for EGFR exon 19 or 21 mutations, ALK translocations or ROS1 fusions.
- Prior pneumonectomy, radiotherapy (including mediastinal radiotherapy), chemotherapy, immune-check inhibitors or targeted therapy for lung cancer within the last 3 years before registration.
- Previously treated brain metastases that are radiologically non-stable.
- Notes:
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- Patients with previously treated brain metastases, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention, can participate. These treated brain metastasis will count as metastasis in the definition of oligometastatic disease.
- Symptomatic brain metastases should be treated with surgery and/or stereotactic radiotherapy/ radiosurgery as soon as possible after diagnosis. If surgery is considered it must be applied before enrolment. Radiotherapy can be performed at any time.
- History of any solid or hematological malignancy in the past 3 years before registration.
- Exceptions include patients who underwent successful definitive treatment of basal or squamous cell carcinoma of the skin, or any in-situ carcinoma(s).
- Any uncontrolled, intercurrent illness or clinical situation that would, in the judgment of investigator, limit compliance with study requirements.
- Any uncontrolled active infection, defined as an infection ≥ grade 3 according to CTCAE version 5.0.
- Any autoimmune disease that has required systemic treatment in the past 2 years (defined as any use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- Replacement therapy (e.g., thyroxine for hypothyroidism or insulin for type I diabetes) is not considered a form of systemic treatment.
- The following treatments are allowed:
- Intranasal, inhaled and topical steroids as well as local steroid injections (e.g., intra articular injection).
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
- Systemic corticosteroid replacement therapy for adrenal or pituitary insufficiency.
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Known active hepatitis B or C, defined as a positive HBV surface antigen (HBsAg) result or positive HCV RNA.
- Known active HIV infection, defined as >200 copies of HIV per ml of blood.
- History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or history of non-infectious pneumonitis that required systemic glucocorticoids to assist with management.
- A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥12 months prior to registration.
- Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 2 weeks prior to the first dose of cemiplimab.
- Patients who require brief courses of steroids (e.g., as prophylaxis for imaging studies due to hypersensitivity to contrast agents) can be included.
- Participation in any other clinical study involving an investigational drug or device within 4 weeks before registration.
- History of documented allergic reaction or acute hypersensitivity reaction attributed to antibody treatments.
- Sensitivity to any of the study interventions, or components thereof, or other allergy that, in the opinion of the investigator, contraindicates participation in the study.
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol, understanding and completion of questionnaires and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial
- At randomization Prior to treatment allocation for the consolidation phase an additional set of selection criteria need to be met and stratification factors provided.
- Use of immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 2 weeks prior to the first dose of cemiplimab/placebo. Patients who require brief courses of steroids (e.g., as prophylaxis for imaging studies due to hypersensitivity to contrast agents) can be included.
Trial locations and contacts
12 sites in 5 countries.
12 sites in 5 countries
Belgium3 sites
Cliniques Universitaires Saint-Luc
Brussels
CHU Helora Pole Hospitalier Jolimont
Haine-Saint-Paul
CHU Mont Godinne - UCL Namur
Yvoir
Italy3 sites
Azienda Unita Locale Socio-Sanitaria N. 9-Mater Salutis Hospital
Legnano
AUSL Della Romagna - Ospedale Santa Maria delle Croci
Ravenna
Azienda Ospedaliero - Universitaria "Santa Maria della Misericordia" di Udine
Udine
Spain3 sites
Hospital De La Santa Creu I Sant Pau
Barcelona
UOMi Cancer Center
Barcelona
University Hospital Virgen del Rocio
Seville
France2 sites
CH de La Cote Basque - Saint Leon
Bayonne
Institut Paoli-Calmettes
Marseille
About this study
This is a multi-center, double-blind, placebo-controlled randomized phase II study to assess whether continuation of cemiplimab treatment (for up to 12 months) increases progression-free survival (PFS) as compared to placebo in patients with a stage IV, synchronous, oligometastatic non-small cell lung cancer (NSCLC) who have not progressed following 4 cycles of cemiplimab with our without platinum-based chemotherapy and radical treatment.
Eligible patients are randomized with a 1:1 ratio to either the cemiplimab or placebo group and will undergo disease assessment (e.g. imaging, blood tests) at regular follow-up visits.
- Conditions
- NSCLC Stage IV
- Being tested
- Cemiplimab, Placebo
- Keywords
- NSCLC, cemiplimab, immunotherapy, oligometastatic disease, radical treatment
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CemiplimabDrug
Cemiplimab is provided in a 10 ml glass vial
PlaceboDrug
standard saline solution
| Study group | Role | What they receive |
|---|---|---|
| Cemiplimab | Experimental | Cemiplimab IV 350 mg every 3 weeks for up to 12 months or until progression or discontinuation Receives: Drug: Cemiplimab |
| Placebo | Placebo comparator | Placebo (saline solution) IV every 3 weeks for up to 12 months or until progression or discontinuation Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
PFS is defined as the time from the date of randomization until first occurrence of any of the following events:
- Disease progression at any site: loco-regional progression/recurrence (related to primary tumour); progression/recurrence of oligometastatic lesions initially present at registration
- Development of new metastatic lesions
- Death due to any cause.
Disease progression will be assessed using the RECIST 1.1 criteria.
Measured: 9 years from first patient randomized
Secondary outcomes (9)
Overall survival (OS)
OS is defined as the time from the date of randomization until date of death, for any reason
Measured: 6 years from first patient randomized
Time to disease progression
Time to disease progression is defined as the time from the date of randomization to the date of first occurrence of any of the following events:
- Disease progression at any site: loco-regional progression/recurrence (related to primary tumour); progression/recurrence of oligometastatic lesions initially present at registration
- Development of new metastatic lesions
- Death due to progressive disease.
Measured: 6 years from first patient randomized
Time to development of new metastatic lesions
Time to development of new metastatic lesions is the time interval from the date of randomization to the date of first occurrence of any of the following events:
- Development of new metastatic lesions not initially present at registration,
- Death due to progressive disease.
Measured: 6 years from first patient randomized
Time to progression in oligometastatic lesions initially present at registration
Time to progression in oligometastatic lesions initially present at registration is the time interval from the date of randomization to the date of first progression/recurrence in at least one of the oligometastatic lesions initially present at registration
Measured: 6 years from first patient randomized
AEs according to NCI-CTCAE v5.0 and SAEs
This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, for adverse event reporting
Measured: 9 years from first patient randomized
Patient reported QoL as measured by the EORTC QLQ-C30 questionnaire
This questionnaire is composed of 30 individual questions that are scored into 15 multi-item and single-item scales according the EORTC scoring manual. These include five functional scales (physical, role, emotional, social, and cognitive), nine symptom scales (fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulties) and a global health status/QoL scale.
The functional and symptom questions follow the same structure using a 4-point Likert scale with responses from "not at all" to "very much".
The questions on global health an QoL use a 7-point Likert scale with responses from "very poor" to "excellent".
Measured: 9 weeks from last patient last treatment
Patient reported QoL as measured by the IL316 questionnaire - self assessment of treatment side effects
This questionnaire includes self-assessment of treatment side effects, most notable pneumonitis.
The questions follow the same structure using a 4-point Likert scale with responses from "not at all" to "very much" and are scored according to the scale structure of their respective source questionnaire.
Measured: 9 weeks from last patient last treatment
Patient reported QoL as measured by the IL316 questionnaire - questions from EORTC QLQ-LC29 questionnaire
This questionnaire includes 8 questions from the EORTC lung cancer specific module (QLQ-LC29) were selected: the coughing domain scale (2 questions), the dyspnoea scale (3 questions), chest pain (1 question) and physical capabilities (1 question).
The questions follow the same structure using a 4-point Likert scale with responses from "not at all" to "very much" and are scored according to the scale structure of their respective source questionnaire.
Measured: 9 weeks from last patient last treatment
Patient reported QoL as measured by the IL316 questionnaire - questions from EORTC QLQ-ELD14 questionnaire
This questionnaire includes 1 item from the validated QLQ-ELD14 questionnaire to include self-assessment on treatment burden: "How much has your treatment been a burden to you?" The questions follow the same structure using a 4-point Likert scale with responses from "not at all" to "very much" and are scored according to the scale structure of their respective source questionnaire.
Measured: 9 weeks from last patient last treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2024
- Study start14 Jan 2025
- Primary completionJan 2030 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLC Stage IVStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 136 participants (estimated)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Dirk de Ruysscher, MD, Study chair, Maastro Clinic - Maastricht Radiation Oncology, Maastricht, NetherlandsFrank Aboubakar Nana, MD, Study chair, Cliniques Universitaires Saint-Luc, Brussels, Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06219317
- Sponsor's protocol ID
- EORTC-2029-LCG
- Acronym
- ICARS
- Status last verified
- Jun 2026
- First submitted
- 3 Jan 2024
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No