Maintenance With OSE2101 Plus FOLFIRI, or FOLFIRI After FOLFIRINOX-based Induction Therapy in Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma (TEDOPAM)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Association Gercor

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518139-12-00

EudraCT number

2017-004548-40

ClinicalTrials.gov

NCT03806309

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the overall survival (OS) of OSE2101 plus FOLFIRI or FOLFIRI alone as maintenance therapy in patients with locally advanced or metastatic PDAC, HLA-A2 positive, having experienced 4-month induction chemotherapy with FOLFIRINOX without disease progression

Secondary objectives 7

1. To assess the progression-free survival (PFS)
2. To assess the safety profile
3. To assess objective response rate (ORR)
4. To assess health-related Quality of life (HRQoL)
5. To assess Q-TWiST (Quality-Adjusted Time Without Symptoms of Disease or Toxicity of Treatment)
6. To assess predictive markers of response (biology, imaging)
7. To assess whether sarcopenia is associated with immune-related AEs (imAEs) in patients treated by OSE2101 alone or with nivolumab (for patient randomized in the first part of the study), and with AEs in patients treated with chemotherapy

Conditions and MedDRA coding

locally advanced or metastatic Pancreatic ductal adenocarcinoma

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Signed and dated informed consent document, willing and able to comply with protocol requirements
2. Adequate organ function, as defined by the following: - Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) - Total serum bilirubin < 1.5 ULN - Prothrombin ratio > 70% - Serum albumin ≥ 2.8 g/dL - Hemoglobin ≥ 10,0 g/dl - White blood cell count (WBC) ≥ 3,000/μL - Absolute neutrophil count (ANC) ≥ 1,500/μL - Platelets ≥ 100,000/μL - Serum creatinine ≤ 1.5 ULN or creatinine clearance > 50 mL/min (MDRD)
3. Life expectancy ≥ 3 months
4. Women participants of childbearing potential must have a negative serum pregnancy test within the 3 days prior to the first treatment administration until 180 days after the last dose of FOLFIRI, and after the last dose of OSE2101 for women and 90 days after the last dose of OSE2101 for men. Both women participants of childbearing potential and men participants who are sexually active with women of childbearing potential must agree to use a reliable method of birth control (i.e. pregnancy rate < 1% per year);
5. Registration in a national health care system (PUMA included)
6. Histologically or cytologically proven PDAC
7. Age ≥ 18 years
8. ECOG Performance Status (PS) 0-1
9. HLA-A2 genotype
10. Recurrent or advanced disease not amenable to surgery with curative intent (previous resection of primary tumor allowed)
11. Measurable or evaluable (radiologically detectable disease which does not fulfill RECIST criteria for measurable disease) lesions according to RECIST v1.1 criteria (CT-scan < 4 weeks)
12. Stable disease or tumor response according to RECIST v1.1 after a 4-month (8 cycles, CT-scan at C8 ± 2 weeks) course of first-line FOLFIRINOX or modified FOLFIRINOX induction chemotherapy
13. Have archival tissue sample that has been identified and confirmed as available for study, or newly obtained core or excisional biopsy of a tumor lesion

Exclusion criteria 21

1. Obstructive jaundice (bilirubin > 1.5 ULN) without adequate biliary drainage
2. Any systemic steroid therapy (> 10 mg daily dose of prednisone or equivalent) for more than seven days one month before inclusion
3. Allograft recipient
4. Active HBV, HCV, or HIV infection
5. Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri
6. Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of neuropathy, alopecia, and the laboratory values defined in the inclusion criteria
7. Known active central nervous system metastases and/or carcinomatous meningitis; patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids at a dose > 10 mg/day of prednisone or equivalent for at least 14 days prior to trial treatment
8. Uncontrolled massive pleural effusion or massive ascites
9. History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, that has required systemic treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
10. Evidence of interstitial lung disease, any active, non-infectious pneumonitis, or known active tuberculosis
11. Active uncontrolled infection, or current unstable or uncompensated respiratory or cardiac conditions, or bleeding
12. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
13. Live vaccine administration within 30 days prior to the first dose of study treatment
14. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the participant, in the opinion of the treating investigator
15. Known or suspected drug hypersensitivity to OSE2101 vaccine
16. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
17. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product
18. Treatment with any investigational medicinal product within 28 days prior to study entry
19. Prior intolerance/severe toxicity with 5FU or irinotecan (including DPD and UGT1A1 deficiency)
20. Pregnancy/lactation
21. Tutelage or guardianship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Evaluable patients for OS rate at 12 months will be patients alive at 12 months and patients dead within 12 months; patients lost to follow-up before 12 months without confirmation of death will be non-evaluable. The OS is defined according to the DATECAN consensus as the time from randomization to death for any reason. In the absence of confirmation of death, survival time will be censored at the date of the last clinical assessment.

Secondary endpoints 7

1. PFS by centralized review of CT-scan imaging.
2. All grade and severe (grade 3-5) toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
3. Response according to RECIST v1.1 77 (centralized review of CT-scan imaging)
4. HRQoL assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire
5. Q-TWiST
6. Potential predictive biomarkers (blood and tumor tissue)
7. Immune-related AEs (imAEs) according to sarcopenia

Investigational products

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

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Association Gercor

Sponsor organisation

Association Gercor

Address

151 Rue Du Faubourg Saint Antoine

City

Paris

Postcode

75011

Country

France

Scientific contact point

Organisation

Association Gercor

Contact name

GARCIA-LARNICOL

Public contact point

Organisation

Association Gercor

Contact name

GARCIA-LARNICOL

Locations

1 EU/EEA country · 34 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 6 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