IFCT-2401 SPORADIC a multicenter randomized open label phase II study evaluating the efficacy and the tolerance of adding cemiplimab to Sequential hyPOfractionated chemoRADiotherapy in unfit or elderly patients with unresectable stage III non-small cell lung cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intergroupe Francophone De Cancerologie Thoracique

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Nov 2025 → ongoing

Decision date (initial)

2024-12-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

REGENERON · IFCT

External identifiers

EU CT number

2024-517316-29-00

ClinicalTrials.gov

NCT06656598

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To determine the efficacy of sequential strategy (neoadjuvant chemoimmunotherapy prior to hypofractionated radiotherapy) in patients with stage III NSCLC mesuread by progression-free survival (PFS).

Secondary objectives 5

1. To evaluate efficacy of sequential strategy mesured by Objective response (ORR) and disease control (DCR) rates according to RECIST 1.1 criteria, by PFS rate at 12 months, 18 months and 3 years by treatment arm and by OS curve and OS rate at 12 months, 18 months and 3 years by treatment arm.
2. To evaluate tolerance of neoadjuvant chemoimmunotherapy before hypofractionated radiotherapy.
3. To evaluate the impact of neoadjuvant treatment on respiratory function.
4. To evaluate the quality of life of patients receiving neoadjuvant chemoimmunotherapy before hypofractionated radiotherapy.
5. To evaluate tolerance of consolidation immunotherapy.

Conditions and MedDRA coding

Unresectable stage III Non-Small Cell Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Patients must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
2. Renal and hepatic function: estimated creatinine clearance ≥ 45 ml/min, bilirubin ≤1.5xULN, AST ALT ≤3xULN, Albumin ≥28g/dl.
3. Participant has national health insurance coverage.
4. Effective method of contraception during the treatment and during the 6 months following the last dose for patients of childbearing potential and for male subjects who are sexually active with a woman of childbearing potential.
5. Patients must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
6. Age ≥ 18 years.
7. Histologically or cytologically confirmed locally advanced NSCLC stage IIIA non resectable, IIIB or IIIC accordingly to 8th classification TNM, UICC 2015.
8. Unfit or elderly patients as defined below: ≥ 70 years ; PS 0 to 1 ; Charlson sccore : watever OR < 70 years ; PS 0 to 1 ; Charslon score ≥ 3 OR < 70 years ; PS 2 ; Charlson sccore : watever
9. Patients eligible for treatment with sequential radio-chemotherapy validated by multidisciplinary committee.
10. Measurable disease according to RECIST 1.1 per investigator assessment. The radiological assessment has to be done within the timelines indicated
11. Respiratory function: FEV1 ≥ 40% of theoretical value, DLCO ≥ 40%.
12. Bone marrow function: absolute neutrophil count (ANC) ≥ 1.5.109/L, platelets ≥ 100.109/L, hemoglobin ≥ 9 g/dl.
13. Expression of PD-L1 as assessed locally by the investigator center.

Exclusion criteria 26

1. Immunotherapy or chemotherapy contra-indicated.
2. Patients eligible for treatment with concomitant radio-chemotherapy validated by multidisciplinary committee.
3. Stage I or II NSCLC.
4. Previously received a treatment with anti-PD1/PDL1, anti-CTLA, or other antineoplastic immunotherapy or chemotherapy for NSCLC.
5. Histology other than primary non-small cell lung cancer.
6. Known activating EGFR mutation or ALK or ROS1 translocation.
7. Metastatic NSCLC including brain metastasis.
8. Patients not eligible for curative radiotherapy (tumor extension, predictable dose constraints that cannot be met).
9. Severe uncontrolled comorbidities or severe intercurrent disease: acute coronary syndrome less than 3 months old, unstable angina, heart failure with LVEF ≤30%, uncontrolled hypertension, Child B or C cirrhosis, severe sepsis, myocarditis or any other active conditions that would contraindicate chemotherapy, immunotherapy, or radiotherapy in the opinion of the investigator.
10. Weight loss ≥15% of total body weight in the last 6 months.
11. ECOG PS upper 2
12. Active autoimmune pathology. History of autoimmune pathology including myasthenia, Guillain-Barre syndrome, lupus erythematosus, antiphospholipid syndrome, Wegener's granulomatosis, glomerulonephritis, inflammatory bowel disease, vasculitis, sarcoidosis, uveitis. Autoimmune thyroid pathologies under replacement therapy as well as type 1 diabetes under insulin are authorized.
13. History of idiopathic pulmonary fibrosis, organized pneumopathy or signs of active interstitial pulmonary pathology on CT scan.
14. Any immunosuppressive therapy received within 28 days and corticosteroids > 10mg/day of prednisone or equivalent received within 7 days prior the start of chemotherapy excepted hydrocortisone replacement for adrenal insufficiency or pituitary disease not considered immunosuppressive therapy.
15. Chronic active infection including tuberculosis, HIV, hepatitis B (HBsAg positive) or C. Patients with a history of cured hepatitis B (anti HBc and absence of negative HBs antigen) are eligible. In case of hepatitis C (anti HCV Ac) patients are eligible if the HCV PCR is negative.
16. Severe infections (including covid-19 infection) within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
17. History of neoplastic disease (other than NSCLC) less than 3 years old or progressive (except basal cell carcinoma of the skin and carcinoma in situ of the cervix).
18. History of thoracic radiotherapy.
19. Live attenuated vaccine received within 28 days of starting chemotherapy
20. History of organ or bone marrow transplantation.
21. Major surgery within 4 weeks of starting treatment.
22. Patient already included in another therapeutic trial.
23. Positive pregnancy test or breastfeeding woman.
24. Protected adults (under guardianship or curatorship).
25. Inability to undergo medical monitoring of the study (for geographical, social and/or physical reasons).
26. Patients unable to understand the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS)

Secondary endpoints 9

1. Objective response (ORR) and disease control (DCR) rates according to RECIST 1.1 criteria.
2. PFS rate at 12 months, 18 months and 3 years by treatment arm.
3. OS curve and OS rate at 12 months, 18 months and 3 years by treatment arm.
4. Neoadjuvant chemoimmunotherapy : Grade 3-4 toxicity rates by treatment arm according to CTCAE v5.0 up to 90 days after the end of immunotherapy
5. Percentage of discontinuation after two cycles of systemic therapy.
6. Toxic death rate.
7. Variation of respiratory function tests before neoadjuvant therapy and after neoadjuvant therapy (just before radiation) and after, at 3, 6 and 12 months.
8. Global and specific quality of life questionnaire QLQ-C30 QLQ-LC29.
9. Consolidation immunotherapy : Acute and late grade 3-4 toxicity rates by treatment arm according to CTCAE v5.0 up to 90 days after the end of immunotherapy.

Investigational products

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

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intergroupe Francophone De Cancerologie Thoracique

Sponsor organisation

Intergroupe Francophone De Cancerologie Thoracique

Address

10 Rue De La Grange Bateliere

City

Paris

Postcode

75009

Country

France

Scientific contact point

Organisation

Intergroupe Francophone De Cancerologie Thoracique

Contact name

Contact

Public contact point

Organisation

Intergroupe Francophone De Cancerologie Thoracique

Contact name

Contact

Third parties 1

Locations

1 EU/EEA country · 32 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 7 files

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

Application history

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