Study to evaluate the impact of VCN-01 on the overall survival of patients with advanced pancreatic cancer treated with standard therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Theriva Biologics S.L.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Nov 2022 → 29 Mar 2025

Decision date (initial)

2024-10-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Theriva Biologics, S.L.

External identifiers

EU CT number

2024-511290-30-00

EudraCT number

2022-000897-24

ClinicalTrials.gov

NCT05673811

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To evaluate the time from randomization until death in both arms (OS).
To evaluate the safety and tolerability of VCN-01, IV administered at Week 1 and Week 14 in Arm II.

Secondary objectives 6

1. To evaluate the time to progression (TTP) or PFS.
2. To determine the ORR.
3. To determine the disease control rate (DCR) (stable disease [SD] + PR + complete response [CR]).
4. To determine the landmark 1-year survival and PFS at the 1-year landmark.
5. To evaluate the duration of response (DoR).
6. To assess changes in tumor marker Ca 19.9 measured every 4 weeks while on study.

Conditions and MedDRA coding

Metastatic Pancreatic Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Written informed consent obtained prior to any study-specific procedures or assessments.
2. Male/female patients aged 18 years or over.
3. Patients with histologically or cytologically confirmed, first line metastatic pancreatic adenocarcinoma stage IV de novo, who never received previous systemic treatment for their pancreatic cancer for which the established therapy is nab-paclitaxel/gemcitabine (clinical SoC). All patients must have at least one measurable tumor lesion that can be imaged for assessments determined by RECIST 1.1.
4. Patients willing to comply with the study treatment.
5. Patients with a minimum life expectancy of 5 months.
6. ECOG performance status of 0 or 1
7. Use of a reliable method of contraception in fertile men and women. Female patients of childbearing potential (i.e., female patients who are not postmenopausal or surgically sterile) must agree to use effective contraception. Male patients must agree to use effective contraception or be surgically sterile. All male patients must use a male condom.
8. Adequate baseline organ function (hematologic, liver, renal and nutritional) verified by laboratory analyses performed within 72 hours prior to dosing*: Hematology: Absolute neutrophil count #1.5x109 /L, Hemoglobin #9 g/dL, Platelets #100x109/L, Coagulation (*except in patients on anticoagulants), Prothrombin time or international normalized ratio #1x upper limit of normal (ULN), Activated partial thromboplastin time #1.2xULN Hepatic:Total bilirubin #1.5xULN, ALT and AST #2.5xULN (if there are no liver metastases), ALT and AST <5xULN, and bilirubin <1.5xULN (if there are liver metastases) Renal: Serum creatinine #1.5xULN, and if >1.5xULN: Estimated creatinine, clearance >50 mL/min using Cockcroft and Gault formula Nutritional: Serum Albumin #30 g/L

Exclusion criteria 20

1. Patients not willing to complete the study procedures for geographic, psychiatric, or social reasons.
2. Active infection or other serious illness or autoimmune disease at the moment of randomization. Active infection includes tuberculosis (TB; clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (HBV; positive HBV surface antigen [HBsAg] result), hepatitis C (HCV; positive HCV Ribonucleic acid [RNA]), or human immunodeficiency virus (positive HIV 1/2 antibodies). HBV carriers (patients positive or HBsAg) or those patients requiring antiviral therapy treatment for HBV virus or HCV are not eligible to participate. However, the following patients are eligible to participate in the study: - Patients with past or resolved TB are eligible; - Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible. Blood HBV DNA must be obtained and must be negative in these patients prior to treatment; - Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
3. Treatment with live attenuated vaccines in the last 3 weeks and with the adenovirus type-5 (Ad5)-based COVID-vaccine in the last 12 weeks before the administration of study treatment.
4. Known chronic liver disease (liver cirrhosis, chronic hepatitis). If there is a suspect of hepatic fibrosis, a fibroscan must be performed; patients with a value #9.5 kPa will be excluded. Note: Transient elastography (Fibroscan) is a non-invasive method for the assessment of hepatic fibrosis.
5. Treatment with another investigational agent within five of that treatment’s half-lives prior to infusion of study treatment.
6. Viral syndrome diagnosed during the 2 weeks before start of study treatment administration.
7. Chronic immunosuppressive and/or disease modifying therapy, except inhaled corticosteroids, and oral or IV corticosteroids with a dose lower than 10 mg prednisone or equivalent/day (exception: dexamethasone 1 mg/day as maximum).
8. Concurrent malignant hematologic or solid disease. Patients with a prior history of cancer can be allowed if complete remission for at least 3 years.
9. Patients in close contact (e.g., living in same house) with immunosuppressed patients (i.e., patients with chronic immunosuppressive therapy including high dose of corticosteroids, patients with acquired immunodeficiency syndrome (AIDS), and other chronic immune system diseases).
10. Patients with Li Fraumeni syndrome or with previously known retinoblastoma protein pathway germline deficiency.
11. A female patient, who is pregnant or lactating.
12. Patients receiving full-dose anticoagulant therapy or in whom these therapies cannot be withdrawn 2 days prior and 2 days after VCN-01 administration. Patients with uncontrolled coagulopathy should be excluded.
13. Untreated brain metastases and/or leptomeningeal carcinomatosis with progressive symptoms despite corticosteroid coverage. Patients with brain metastases with stable symptoms can be included.
14. Any other condition, disease, metabolic dysfunction (e.g., uncontrolled diabetes mellitus), active or uncontrolled infection/inflammation, physical examination finding, mental state or clinical laboratory finding that would contraindicate participation in the clinical study due to safety concerns or compliance with clinical study procedures.
15. Patients with previous pneumonitis or interstitial lung disease.
16. Patients with pre-existing sensory neuropathy >G1.
17. Patients with risk factors for bowel perforation.
18. Patients with QT interval corrected by Fridericia (QTcF) assessment >450 ms for men or >470 ms for women and left ventricular ejection fraction (LVEF) evaluation less than 50% measured by ECHO or multigated acquisition scan.
19. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
20. Subjects, for whom first line treatment options other than the combination Gemcitabine/Nab-Paclitaxel are recommended by the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. OS
2. Safety and tolerability

Secondary endpoints 6

1. PFS or TTP
2. ORR
3. DCR (SD + PR + CR)
4. Landmark 1-year survival and PFS at the 1-year landmark
5. DoR
6. Changes in tumor marker Ca 19.9

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Theriva Biologics S.L.

Sponsor organisation

Theriva Biologics S.L.

Address

Calle Torrent De Can Ninou Naves 5-6

City

Parets Del Valles

Postcode

08150

Country

Spain

Scientific contact point

Organisation

Theriva Biologics S.L.

Contact name

Theriva Biologics S.L.

Public contact point

Organisation

Theriva Biologics S.L.

Contact name

Theriva Biologics S.L.

Third parties 3

Locations

1 EU/EEA country · 10 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

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