Microbiota Modification for Immuno-Oncology in Hepatocellular Carcinoma - “Mother”

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre De Lutte Contre Le Cancer Eugene Marquis

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Mar 2025 → ongoing

Decision date (initial)

2024-05-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate efficacy of atezolizumab-bevacizumab with bacterial supplementation in HCC patients progressive to first line immunotherapy

Secondary objectives 1

1. To evaluate safety of atezolizumab-bevacizumab with bacterial supplementation in HCC patients progressive to first line immunotherapy.

Conditions and MedDRA coding

Hepatocellular carcinoma

Regulatory references

Scientific advice from competent authorities

Federal Agency For Medicines And Health Products, Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male or female
2. Aged ≥18 years at time of signing informed consent
3. Presenting with HCC, diagnosed either by histological or radiological criteria as described by EASL
4. Locally advanced or metastatic and/or unresectable HCC according a Multidisciplinary Team meeting
5. Progressive disease after exposure to standard-of-care approved first-line immunotherapy-based
6. Child-Pugh A within 7 days prior to inclusion
7. ECOG Performance status 0 to 1
8. Adequate hematological (Hemoglobin >8.5g/dL, platelets >60G/L, neutrophils >1.5G/L) and renal (creatinine clearance > 50 mL/min according to Cockcroft or MDRD formula) functions
9. Disease measurable by RECIST 1.1
10. Signed written Informed consent

Exclusion criteria 19

1. Partial response achieved under first-line immunotherapy-based combination
2. Interstitial lung disease
3. HBV chronic infection with HBV DNA > 100 IU/mL or without antiviral therapy; HBV patients with cirrhosis should be treated
4. HIV infection
5. Immunosuppression, including subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone equivalent)
6. Transplanted liver, or patient with intent for transplantation
7. Has difficulties in swallowing.
8. Has undergone major surgery or significant trauma ≤4 weeks prior to Screening
9. Is currently participating in or has participated in a study with an investigational compound or device within 3 months prior to the first dose of study intervention.
10. Has a systemic infection or other serious infection requiring systemic treatment within 30 days prior to screening
11. Has a history of hypersensitivity to EXL01 and/or any excipients, which are listed in the IB, and/or to soybean or soy-containing products
12. CTCAE Grade ≥3 or more toxicity under first-line immunotherapy-based combination or persistent toxicity Grade >1
13. Liver involvement > 50%
14. Presence of major macro vascular invasion (except Vp1/Vp2)
15. Pregnant woman, or breastfeeding or women of child-bearing potential with no adequate contraception
16. Under curatorship, guardianship, safeguard of justice or deprived of liberty
17. History of serious autoimmune disease
18. Specific contra-indication to atezolizumab-bevacizumab: 1) Thromboembolic events in the 3 months prior to inclusion 2) Prior bleeding event due to untreated or incompletely treated esophageal and / or gastric varices within 6 months’ prior inclusion 3) Has a history of hypersensitivity to the atezolizumab or to any of the excipients listed in section 6.1 of the SmPC of atezolizumab and bevacizumab or to any of the excipients listed in section 6.1 of the SmPC 4) Uncontrolled hypertension 5) Clinically significant cardiovascular disease such as pre-existing coronary artery disease, or congestive heart failure 6) Proteinuria
19. specific contra-indication for durvalumab : Has a history of hypersensitivity to the durvalumab or to any of the excipients listed in section 6.1 of the SmPC of durvalumab

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. The Objective Response Rate at W12, defined as the proportion of patients with a Complete objective tumor Response (CR) or a Partial objective tumor Response (PR) from inclusion to week 12. The objective tumor response is defined as the best overall tumor response (BOR) observed in a patient within all-time points between inclusion to the W12 visit, according to the RECIST 1.1.
2. The overall tumor response observed at first imaging after 2 cycles of standard of care immunotherapy (W6 for patients treated with atezolizumab-bevacizumab cohort or W8 for patients treated with durvalumab- tremelimumab cohort), W12, M6, M12 according to the mRECIST, RECIST 1.1 and iRECIST criteria.
3. The ORR at W12, according to the mRECIST, and iRECIST criteria.
4. The Disease control rate (DCR), as the proportion of patients with BOR as CR, PR or stable disease (SD) defined according to the mRECIST, RECIST 1.1 and iRECIST criteria at W12, M6, M12.
5. The Progression-Free Survival, defined as the time from patient inclusion to progression or death from any cause.
6. The Overall Survival, defined as the time from patient inclusion to death from any cause.
7. The ORR at M6, M12, according to the mRECIST, RECIST 1.1 and iRECIST criteria.

Secondary endpoints 1

1. Frequency of adverse events, graded according to the last up-to-date NCI-CTCAE classification. Adverse events are monitored from inclusion to 30 days after the last EXL01 intake.

Investigational products

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

Test 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre De Lutte Contre Le Cancer Eugene Marquis

Sponsor organisation

Centre De Lutte Contre Le Cancer Eugene Marquis

Address

Avenue La Bataille Flandre Dunkerque, Cs 44229 Cs 44229

City

Rennes Cedex

Postcode

35042

Country

France

Scientific contact point

Organisation

Centre De Lutte Contre Le Cancer Eugene Marquis

Contact name

Héloise BOURIEN

Public contact point

Organisation

Centre De Lutte Contre Le Cancer Eugene Marquis

Contact name

Héloise BOURIEN

Locations

1 EU/EEA country · 6 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 5 files

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

Application history

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