Single-arm, multicenter, phase II study of immunotherapy in patients with type B3 thymoma and thymic carcinoma previously treated with chemotherapy - (Nivothym)

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]

Decision date (initial)

2024-08-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bristol-myers Squibb International Corporation · European Organisation for Research and Treatment of Cancer (EORTC)

External identifiers

EU CT number

2023-508658-24-00

EudraCT number

2015-005504-28

ClinicalTrials.gov

NCT03134118

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To assess PFS rate (PFSR) at 6 months in patients treated with nivolumab or the combination of nivolumab and ipilimumab, with
relapsed/advanced thymic carcinoma and type B3 thymoma not amenable to curative-intent radical treatment and previously treated with platinum-based chemotherapy

Secondary objectives 3

1. To assess Overall Response Rate (ORR), Disease Control Rate (DCR) and duration of response of nivolumab or nivolumab in combination with ipilimumab in this study population
2. To assess OS and PFS in this study population treated with nivolumab
3. To assess the safety of nivolumab in this study population

Conditions and MedDRA coding

type B3 thymoma and thymic carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Relapsed/advanced thymoma B3 or thymic carcinoma not amenable to curative-intent radical treatment
2. At least one previous line of platinum-based chemotherapy for advanced disease
3. Radiological progression documented per RECIST 1.1 during or after completion of previous line therapy
4. Presence of measurable disease according to RECIST 1.1.
5. At least 18 years
6. WHO Performance Status (PS) 0-2
7. Availability of FFPE tumor tissue (preferentially a tumor block or 10 unstained slides), notably for PD-L1 immunohistochemistry (IHC) expression assessment. Archival material is allowed. Tissue must be considered adequate (assessed by a local pathologist) for characterization of PD-L1 status as per procedure manual
8. Adequate hematological function: -White blood count ≥ 2 × 109/L; -Haemoglobin >9 g/dL; -Platelet count >100 × 109/L
9. Adequate liver function: -Total bilirubin <1.5 × ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL); -LT and/or AST <2.5 × ULN (< 4 x ULN in case of liver metastasis) -Alkaline phosphatase <5 × ULN
10. Adequate renal function: calculated creatinine clearance ≥50 mL/min (according to Cockroft-Gault, see below); -Female CrCl = ((140 - age in years) x weight in kg x 0.85)/ 72 x serum creatinine in mg/dL; -Male CrCl = ((140 - age in years) x weight in kg x 1.00)/72 x serum creatinine in mg/dL
11. Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment
12. Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 5 months for a woman and 7 months for a man after the last study treatment.
13. Female patients who are breast feeding should discontinue nursing prior to the first dose of study medication and must not breast feed during the trial treatment and for a period of at least 5 months following the last administration of trial drug(s)
14. Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion criteria 16

1. Any evidence of active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable (i.e. without evidence of progression by imaging for at least four weeks prior to enrollment and any neurologic symptoms have returned to baseline), and have not received steroids (for a total equivalent dose of more than 10 mg of prednisone per day) for at least 7 days prior to enrollment
2. Prior treatment with anti-PD-1, anti-PD-L1/2, anti-CD137, CTLA-4 modulators
3. Presence of acetylcholine receptor antibodies
4. Current participation in any other clinical research or treatment with an investigational agent or use of an investigational device within 4 weeks of enrollment
5. Known active Hepatitis B (e.g., positive HBsAg result) or C (e.g., HCV RNA[qualitative] is detected) or known history or current evidence of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies)
6. If CT has to be used, known contra-indications for CT with IV contrast
7. History of interstitial lung disease (ILD) OR pneumonitis (other than COPD exacerbation) that has required oral or IV steroids
8. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
9. Live vaccines within 30 days prior to the first dose of study therapy and while participating in study. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, H1N1 flu, rabies, BCG, and typhoid vaccine.
10. Autoimmune paraneoplastic syndrome requiring immunosuppressive or dedicated treatment. Particular attention should be given to detecting any minor myasthenia signs or positive autoantibodies at enrollment
11. History of any other hematologic or primary solid tumor malignancy, unless in remission for at least 5 years. pT1-2 prostatic cancer Gleason score < 6, superficial bladder cancer, non melanomatous skin cancer or carcinoma in situ of the cervix are allowed
12. Previous allogeneic tissue/solid organ transplant
13. Active infection requiring therapy
14. Surgery or chemotherapy related toxicity that have not resolved to a grade 1, with the exception of alopecia, fatigue, neuropathy and lack of appetite /nausea
15. Severe comorbidities that in the opinion of the investigator might hamper participation to the study and/or treatment administration
16. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression Free Survival Rate at 6 months (PFSR-6) per independent radiological review

Secondary endpoints 8

1. Progression Free Survival Rate at 6 months (PFSR-6) according to RECIST 1.1 per local investigator assessment
2. Safety according to CTCAE v4.0
3. Overall Response Rate (ORR) according to RECIST 1.1 per local investigator assessment
4. Disease Control Rate according to RECIST 1.1 per local investigator assessment (DCR)
5. Duration of response according to RECIST 1.1 per local investigator assessment
6. Progression Free Survival (PFS) according to RECIST 1.1 per local investigator assessment
7. Overall Survival (OS)
8. Progression Free Survival for patients continuing treatment after progression

Investigational products

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

Test 2

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

Locations

4 EU/EEA countries · 13 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 28 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