Safety and efficacy of adding immunotherapy combined with stereotactic radiotherapy in patients with limited metastatic pancreatic cancer (MEPANC-1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Feb 2021 → 15 Oct 2024

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514598-23-00

EudraCT number

2020-003945-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

This is an open-label, non-randomized, multicentre phase II study with an initial safety-run in. During the safety run-in phase, we will investigate the safety of combining IMM-101 administration with SBRT in 20 patients with limited metastatic disease in the liver and/or lung. If deemed safe, we will continue inclusion in the second phase of the study with an additional 80 patients in order to evaluate the efficacy of combining IMM-101 treatment with SBRT based on a 100% improvement of progression free survival.
The primary objective of the safety run-in is to determine safety of IMM- 101 combined with SBRT in patients with limited metastatic pancreatic cancer. When this combination is found to be safe, the second phase of the study will be initiated, the primary objective of the phase II is to investigate the potential efficacy of IMM-101 combined with SBRT.

Secondary objectives 8

1. Overall survival calculated from the start of FOLFIRINOX (OS1).
2. Overall survival calculated from start of IMM-101 (OS2).
3. Progression-free survival calculated from the start of IMM-101 (PFS 2) at 12-month to the date of progressive disease of the primary tumour, locoregional recurrence, progression of previously treated lungs and/or liver metastases, the occurrence of new metastases, or death. All included patients will be analysed for this endpoint.
4. Quality of Life.
5. Radiological response rate after IMM-101 and SBRT using iRECIST criteria.
6. Radiological response rate after IMM-101 and SBRT using RECIST criteria (version 1.1).
7. Immunological effects: effect of IMM-101 and SBRT on circulating immune cells.
8. Effect on tumour markers, CA19.9 and CEA.

Conditions and MedDRA coding

Limited metastatic pancreatic cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Histologically confirmed (metastatic) pancreatic cancer, as indicated by a definite cytology/histology report.
2. ≤5 hepatic and/or pulmonary metastases in total.
3. The combined diameter of all liver metastases AND the primary tumour or local recurrence in the pancreas is <9 cm.
4. The combined diameter of all pulmonary metastases is <9 cm.
5. CA 19-9 < 1000 IU/mL after completion of chemotherapy.
6. Age > 18 years and < 75 years.
7. WHO performance status of 0-2.
8. Tumour volume of the primary tumour <7cmx7cmx7cm. Each diameter must not exceed 7 cm.
9. Adequate renal function (eGFR ≥ 30 ml/min).
10. Adequate liver tests (bilirubin < 1.5 times normal; ALAT/ASAT < 5 times normal).
11. Adequate bone marrow function (WBC > 3.0 x 109/L, platelets > 100 x 109/L and hemoglobin > 5.6 mmol/l).
12. Effective contraceptive methods.
13. Written informed consent.
14. Patients who did not complete at least 8 cycles of FOLFIRINOX due to severe toxicity, will be included in the expansion cohort.

Exclusion criteria 19

1. Metastasis in other organs than the lung and liver.
2. Histopathologically proven extra regional lymph node metastasis.
3. Malignant ascites.
4. Liver function insufficient to tolerate the prescribed dose of radiotherapy. To be determined by the treating radiologist.
5. Child-Pugh Classification grade B/C.
6. Lung function insufficient to tolerate the prescribed dose of radiotherapy. To be determined by the treating radiologist.
7. Diffuse liver metastasis pattern on CT scan.
8. Current or previous treatment with immunotherapeutic drugs.
9. Second primary malignancy except in situ carcinoma of the cervix, adequately treated non-melanoma skin cancer, or other malignancy treated at least 3 years previously to diagnosis of pancreatic cancer and without evidence of recurrence.
10. Pregnancy, breast feeding.
11. An active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or other immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
12. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the planned first dose of the study. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
13. History of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies).
14. Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
15. Positive PCR test for presence of SARS-CoV-2 during screening stage.
16. Live virus vaccine within 30 days of planned start of trial treatment.
17. Use of herbal remedies, including traditional Chinese herbal products (e.g., mistletoe).
18. Allergic reaction to M. obuense or had previously received IMM-101.
19. Otherwise deemed unsuitable by the Investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The main endpoint of the first inclusion phase is to determine safety/toxicity of IMM- 101 and SBRT administration in patients with limited metastatic pancreatic cancer.
2. The main endpoint of the second inclusion phase is to asses efficacy of IMM-101 therapy in combination with SBRT in patients with limited metastatic pancreatic cancer.

Secondary endpoints 9

1. Overall survival will be calculated from the start of FOLFIRINOX treatment to death (OS1).
2. Overall survival will be calculated from the start of IMM-101 treatment to death (OS2).
3. Progression free survival will be calculated from the start of IMM-101 treatment to the date of progressive disease of the primary tumour or locoregional recurrence, progression of previously treated lungs and/or liver metastasis, the occurrence of new metastases or death (PFS2).
4. Quality of life. Scoring procedures for the EORTC QLQ-c30 will be varied out according to the corresponding manual. Scores between baseline and week 8 will be compared by using the paired t-test for normally distributed data while the Wilcoxon signed rank test will be used for non-normally distributed data. For visualization, box plots will be generated.
5. Radiological response rate after IMM-101 and SBRT using iRECIST criteria.
6. Radiological response rate after IMM-101 and SBRT using RECIST criteria (version 1.1).
7. Safety/Toxicity according to CTCAE 5.0.
8. Effect on circulating immune cells: pre-treatment (week 0), during treatment (week 2,4,8) and post treatment (week 26) venous blood will be monitored for the frequency and activation state of T cells, NKs, and myeloid subsets and for WT-1 and mesothelin specific T cell responses by flow cytometry and Elispot read-out; inflammatory and suppressive cytokine levels will be assessed in plasma.
9. Tumour-specific immune and tumour marker responses. Pre- and 2x post-treatment CA19.9 and CEA levels will be assessed on blood samples.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Research Physician

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Research Physician

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 5 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