Efecto de la inmunoterapia en pacientes con cáncer de pulmón de células no pequeñas oligometastásico (número limitado de metástasis) después de haber sido tratados con radioterapia y/o cirugía

Overview

Sponsor-declared trial summary

Key facts

Sponsor

European Organisation For Research And Treatment Of Cancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Jan 2025 → ongoing

Decision date (initial)

2024-10-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Regeneron Pharmaceutical, Inc.

External identifiers

EU CT number

2023-508741-40-00

ClinicalTrials.gov

NCT06219317

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Others

To assess whether continuation of cemiplimab treatment (for up to 12 months) increases progression free survival (PFS) as compared to placebo in patients with stage IV, synchronous, oligometastatic NSCLC who have not progressed following 4 cycles of platinum-based chemotherapy plus cemiplimab or cemiplimab alone and who received a radical treatment (primary tumour and metastases) if a complete response was not achieved.

Secondary objectives 4

1. To evaluate the efficacy of continuation of cemiplimab as consolidation treatment in improving overall survival (OS) as compared to placebo.
2. To study the pattern and rate of first progressions over time (time to disease progression, time to progression in oligometastatic lesions initially present, time to development of new metastatic lesions) for the continuation of cemiplimab as consolidation treatment versus placebo.
3. To evaluate the safety and tolerability according to CTCAE v5.0 of the continuation of cemiplimab as consolidation treatment as compared to placebo.
4. To establish the patient-reported tolerability profile of the continuation of cemiplimab as consolidation treatment as compared to placebo.

Conditions and MedDRA coding

Non-small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Registration phase: Histologic or cytologic confirmation of NSCLC. If small-cell elements present, participant will be ineligible.
2. Registration phase: 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.
3. Registration phase: Measurable disease according to RECIST 1.1.
4. Registration phase: Age at registration ≥18 years
5. Registration phase: Eastern Cooperative Oncology Group performance status (ECOG PS)/ World Health Organization (WHO) 0-1.
6. Registration phase: 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 • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤3x ULN (or ≤5x ULN, if liver metastases)
7. Registration phase: Renal function: Glomerular filtration rate (GFR) based on the modification of diet in renal disease (MDRD) equation ≥30 mL/min
8. Registration phase: Bone marrow function: • Haemoglobin ≥9.0 g/dL • Absolute neutrophil count (ANC) ≥1.5 x 10^9/L • Platelet count ≥100 x 10^9/L
9. Registration phase: 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.
10. Registration phase: 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.
11. Registration phase: 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.
12. Registration phase: 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.
13. At randomization: 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.
14. At randomization: Anticipated life expectancy >12 weeks
15. At randomization: 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)
16. At randomization: Renal function: GFR based on MDRD equation ≥30 mL/min
17. At randomization: Bone marrow function: • Haemoglobin ≥9.0 g/dL • ANC ≥1.5 x 10^9/L • Platelet count ≥100 x 10^9/L
18. At randomization: WOCBP must have a negative serum or highly negative urine pregnancy test within 7 days prior to the first dose of consolidation treatment.

Exclusion criteria 19

1. Registration phase: Presence of malignant pleural, pericardial and/or peritoneal effusion.
2. Registration phase: Known active hepatitis B or C, defined as a positive HBV surface antigen (HBsAg) result or positive HCV RNA.
3. Registration phase: Known active HIV infection, defined as >200 copies of HIV per ml of blood.
4. Registration phase: 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.
5. Registration phase: 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.
6. Registration phase: Presence of leptomeningeal carcinomatosis.
7. Registration phase: Tumour known to be positive for EGFR exon 19 or 21 mutations, ALK translocations or ROS1 fusions.
8. Registration phase: Prior pneumonectomy, radiotherapy (including mediastinal radiotherapy), chemotherapy, immune-check inhibitors or targeted therapy for lung cancer within the last 3 years before registration.
9. Registration phase: Previously treated brain metastases that are radiologically non-stable.
10. Registration phase: History of any solid or haematological 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).
11. Registration phase: Any uncontrolled, intercurrent illness or clinical situation that would, in the judgment of investigator, limit compliance with study requirements.
12. Registration phase: Any uncontrolled active infection, defined as an infection ≥ grade 3 according to CTCAE version 5.0.
13. Registration phase: 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)
14. Registration phase: Receipt of live vaccines (including attenuated) within 30 days of first study treatment.
15. Registration phase: Participation in any other clinical study involving an investigational drug or device within 4 weeks before registration.
16. Registration phase: History of documented allergic reaction or acute hypersensitivity reaction attributed to antibody treatments.
17. Registration phase: 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.
18. Registration phase: Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol, understanding and completion of questionnaires and followup schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial
19. At randomization: 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival according to RECIST 1.1

Secondary endpoints 6

1. Overall survival
2. Time to disease progression
3. Time to development of new metastatic lesions
4. Time to progression in oligometastatic lesions initially present at registration
5. AEs according to NCI-CTCAE v5.0 and SAEs
6. Patient-reported symptoms and treatment side-effects as measured by the EORTC QLQ-C30 and IL316 questionnaires.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

European Organisation For Research And Treatment Of Cancer

Sponsor organisation

European Organisation For Research And Treatment Of Cancer

Address

Emmanuel Mounierlaan 83 Bus 11

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Stéphanie Kromar

Public contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Vassilis Golfinopoulos

Third parties 2

Locations

5 EU/EEA countries · 18 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 3 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