A Study of Oncobax®-AK in Patients With Advanced Solid Tumors

NCT ID: NCT05865730

Last Updated: 2023-05-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-01
• Study Completion Date: 2026-06-30

Brief Summary

Akkermansia muciniphila is a naturally occurring bacterium found in the healthy human gastrointestinal tract.

Analysis of the gut microbiota of NSCLC or RCC patients shows that the presence of Akkermansia is associated with the clinical efficacy of immunotherapy. In preclinical models, oral administration of the Akkermansia p2261 strain reverses resistance to PD-1 blockade. In the clinical setting, it is therefore hypothesized that the oral administration of Oncobax®-AK to cancer patients under immunotherapy, but whose gut microbiota is deficient in Akkermansia will restore / improve the efficacy of immunotherapy in patients with NSCLC or RCC.

Conditions

Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 2 - NSCLC

Oncobax-AK (1 capsule) will be administered daily until PD\< excessive toxicity or withdrawal of consent

Group Type: EXPERIMENTAL

Live Bacterial Product - Akkermansia muciniphila

Intervention Type: OTHER

Oral administration of Oncobax-AK to patients deficient in Akkermansia by stool metagenomic analysis.

Phase 2 -RCC

Oncobax-AK (1 capsule) will be administered daily until PD\< excessive toxicity or withdrawal of consent

Group Type: EXPERIMENTAL

Live Bacterial Product - Akkermansia muciniphila

Intervention Type: OTHER

Oral administration of Oncobax-AK to patients deficient in Akkermansia by stool metagenomic analysis.

Interventions

Live Bacterial Product - Akkermansia muciniphila

Oral administration of Oncobax-AK to patients deficient in Akkermansia by stool metagenomic analysis.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Age > 18 years

2. Histologically confirmed Stage IV non-squamous NSCLC or clear cell RCC

3. NSCLC-specific criterion: Best tumor response (by iRECIST) as Stable Disease

4. NSCLC-specific criterion: PD-L1 expression > 50%

5. ECOG Performance Status = 0-1

6. Negative stool PCR test for Akkermansia

7. At least one measurable lesion per iRECIST

8. Hemoglobin ≥ 100 g/L

9. Albumin > 35 g/L

10. Signed informed consent

Exclusion Criteria

1. Symptomatic brain metastases

2. AST or ALT > 5 x ULN

3. Calculated creatinine clearance < 45 ml/min

4. Auto-immune diseases requiring systemic therapy

5. Immunosuppressive therapy (> 10 mg prednisone/day equivalent)

6. Radiotherapy (> 30 Gy) to the lung(s) within 6 months of signed informed consent

7. Active infection

8. Co-morbidities that may increase the risk of treatment-related adverse events

9. Pregnancy

10. Inability to comply with protocol-specific assessments

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EverImmune

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fabrice Barlesi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Gustave Roussy, Cancer Campus, Grand Paris

Locations

CHU Ambroise Paré

Mons, , Belgium

Site Status: RECRUITING

Centre Georges Francois Leclerc

Dijon, , France

Site Status: RECRUITING

Institut Gustave Roussy

Paris, , France

Site Status: RECRUITING

ICANS - Institut de cancérologie Strasbourg

Strasbourg, , France

Site Status: RECRUITING

Countries

Belgium; France

Central Contacts

Alain Thibault, MD

Role: CONTACT

alain.thibault@everimmune.com

+32472196345

Facility Contacts

Stephane Holbrechts, MD

Role: primary

Francois Ghiringhelli, MD, PhD

Role: primary

Laurence Albiges, MD, PhD

Role: primary

Philippe Barthelemy, MD, PhD

Role: primary

References

Derosa L, Routy B, Thomas AM, Iebba V, Zalcman G, Friard S, Mazieres J, Audigier-Valette C, Moro-Sibilot D, Goldwasser F, Silva CAC, Terrisse S, Bonvalet M, Scherpereel A, Pegliasco H, Richard C, Ghiringhelli F, Elkrief A, Desilets A, Blanc-Durand F, Cumbo F, Blanco A, Boidot R, Chevrier S, Daillere R, Kroemer G, Alla L, Pons N, Le Chatelier E, Galleron N, Roume H, Dubuisson A, Bouchard N, Messaoudene M, Drubay D, Deutsch E, Barlesi F, Planchard D, Segata N, Martinez S, Zitvogel L, Soria JC, Besse B. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer. Nat Med. 2022 Feb;28(2):315-324. doi: 10.1038/s41591-021-01655-5. Epub 2022 Feb 3.

Reference Type: BACKGROUND

PMID: 35115705 (View on PubMed)

Derosa L, Routy B, Fidelle M, Iebba V, Alla L, Pasolli E, Segata N, Desnoyer A, Pietrantonio F, Ferrere G, Fahrner JE, Le Chatellier E, Pons N, Galleron N, Roume H, Duong CPM, Mondragon L, Iribarren K, Bonvalet M, Terrisse S, Rauber C, Goubet AG, Daillere R, Lemaitre F, Reni A, Casu B, Alou MT, Alves Costa Silva C, Raoult D, Fizazi K, Escudier B, Kroemer G, Albiges L, Zitvogel L. Gut Bacteria Composition Drives Primary Resistance to Cancer Immunotherapy in Renal Cell Carcinoma Patients. Eur Urol. 2020 Aug;78(2):195-206. doi: 10.1016/j.eururo.2020.04.044. Epub 2020 May 4.

Reference Type: BACKGROUND

PMID: 32376136 (View on PubMed)

Other Identifiers

EV-2101

Identifier Type: -

Identifier Source: org_study_id