RR001, a cell-based gene therapy administered in combination with chemotherapy for the treatment of patients with locally advanced pancreatic cancer. Phase I /IIa clinical trial (open label and non-randomized) to test the effects (safety & efficacy) of increasing doses of RR001.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eir Biotherapies S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Jun 2025 → ongoing

Decision date (initial)

2024-12-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Eir Biotherapies S.r.l.

External identifiers

EU CT number

2024-516019-26-00

EudraCT number

2021-000588-53

ClinicalTrials.gov

NCT06861452

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Dose response, Pharmacodynamic, Others, Safety

1. To determine the safety of intra-tumoral injection of the RR001 administered by ultrasound (US) guided injections in combination with standard of care therapy based on GEM/Nab-PTX
2. To establish the maximal tolerated dose (MTD) and recommended phase IIb dose (RP2D) of intratumoral injections of RR001 after three dose levels delivery in combination with standard of chemotherapy

Secondary objectives 7

1. To determine the feasibility of intra-tumoral administration of the RR001 by ultrasound (US) guided injections in combination with standard of care therapy based on GEM/Nab-PTX
2. To determine the efficacy of the use of RR001 in combination with standard of care therapy based on 2 cycles of GEM/Nab- PTX by target tumor response, assessed by objective radiologic (CT+NMR) assessment using RECIST 1.1 criteria
3. To determine Overall response rate (ORR) assessed by objective radiologic (CT+NMR) assessment using RECIST 1.1 criteria
4. Percentage of patients successfully undergoing to surgery and percentage of pathological resection (R0 vs. R1 vs. R2)
5. Time to disease progression (TTP), progression free survival (PFS) and overall survival (OS)
6. Circulation tumoral markers modulation (CEA, CA19.9)
7. Quality of life (EORTC QLQ-C30, QLQ-PAN26)

Conditions and MedDRA coding

Ductal adenocarcinoma of pancreas

Regulatory references

Scientific advice from competent authorities

Italian Medicines Agency, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Patients with confirmed pancreatic ductal adenocarcinoma
2. Safe hematologic profile
3. Negative serum pregnancy test for females of childbearing potential within days of starting treatment
4. Patients with no evidence of peritoneal or hematogenous metastasis
5. Patients classified as non-resectable locally advanced pancreatic carcinoma (LAPC) based on imaging (TC and NMR), on multidisciplinary staff evaluation by at least an oncologist, radiologist and a qualified digestive surgeon and accounting for AJCC/UICC TNM and clinical staging
6. Measurable tumor according RECIST criteria v 1.1
7. Low tumor burden with at least one lesion equal/less than 3,5 cm that is suitable for US guided injection (and needle biopsy)
8. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
9. Patients must be eligible for chemotherapy treatment (based on standard of care)
10. Patient older than 18 years of age
11. Adequate hepatic and kidney function
12. Willingness and ability to comply with the scheduled visits, treatment plan, imaging procedures, laboratory tests and other study procedures, including lipoaspirate collection (liposuction)

Exclusion criteria 20

1. Patient with pancreatic cystic tumor or pancreatic pseudocyst
2. Patient with pancreatic tumor different from adenocarcinoma (endocrine, metastases)
3. Patients with unknown stage or recurrent pancreatic cancer
4. Patients with immunosuppression or susceptibility to viral infection
5. Patients with HIV, hepatitis B, hepatitis C, HTLV-I/II, Treponema Pallidum infections
6. Patients with liver cirrhosis or other documented liver diseases
7. Patient contraindication to use chemoterapy treatments
8. Previous radiotherapy and/or chemotherapy for PDAC
9. Previous haematopoietic stem cell or organ transplantation
10. Irreversible cardiac arrhythmias requiring permanent medication
11. Heart insufficiency (> grade II, New York Heart Association NYHA criteria)
12. History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris
13. Uncontrolled hypertension
14. Other malignancies within the past 2 years (not including basal cell carcinoma of the skin, prostate cancer or in situ cervix carcinoma, in situ melanoma)
15. Active autoimmune disease
16. Use of any investigational agents within 21 days from the administration of study treatment
17. Patient has had major open surgery within the 3 months prior to the administration of study treatment
18. Uncontrolled intercurrent illness including but not limited to psychiatric illness/social situations that in the opinion of the Investigator would compromise compliance of study requirements or put the patient at unacceptable risk
19. Suspected or known allergy or hypersensitivity to fluoroquinolones including but not limited to ciprofloxacin
20. Suspected or known allergy or hypersensitivity to protamine sulfate or protamine containing products. Including but not limited to patients who have previously undergone procedures such as coronary angioplasty or cardio-pulmonary bypass, which may involve the use of protamine, diabetics who have been treated with protamine insulin, patients allergic to fish, and men who have undergone a vasectomy or are infertile and may have antibodies to protamine

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. To investigate the safety of intratumoral injections of the gene therapy product RR001 administered by US guided injection in combination with standard of care therapy based on GEM/Nab-PTX
2. To establish the MTD and RP2D of intratumoral injections of RR001 after three dose levels delivery in combination with standard of care therapy

Secondary endpoints 9

1. To investigate the feasibility of intratumoral injections of the gene therapy product RR001 administered by US guided injection in combination with standard of care therapy based on GEM/Nab-PTX
2. Antitumor activity: Target tumor response will be assessed by objective radiologic assessment using RECIST 1.1 criteria
3. Response rate: the overall response rates (ORR) for objective response (complete, partial responses, stable disease, progressive disease) will be assessed by objective radiographic assessment using RECIST 1.1 criteria
4. Percentage of patients successfully undergoing to surgery and percentage of pathological resection (R0 vs. R1 vs. R2)
5. Time to disease progression (TTP)
6. Overall survival (OS)
7. Tumor markers in serum (CEA, CA19.9 if present at the diagnosis)
8. Quality of life by scoring of quality of life according to the EORTC QLQ-C30 and QLQ-PAN26
9. Progression free survival (PFS)

Investigational products

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

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eir Biotherapies S.r.l.

Sponsor organisation

Eir Biotherapies S.r.l.

Address

Piazza Costituente 33

City

Mirandola

Postcode

41037

Country

Italy

Scientific contact point

Organisation

Eir Biotherapies S.r.l.

Contact name

Giorgio Mari

Public contact point

Organisation

Eir Biotherapies S.r.l.

Contact name

Giorgio Mari

Third parties 5

Locations

1 EU/EEA country · 1 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 12 files

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

Application history

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