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

A Phase 1/2 Study of Oncobax®-AK Administered in Combination With Immunotherapy To Patients With Advanced Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Other: Live Bacterial Product - Akkermansia muciniphila

• Study Type: Interventional
• Enrollment (Anticipated): 122
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alain Thibault, MD; Phone Number: +32472196345; Email: alain.thibault@everimmune.com

Study Locations

• Belgium
  • Mons, Belgium
    • Recruiting
    • CHU Ambroise Pare
    • Contact: Stephane Holbrechts, MD
• France
  • Dijon, France
    • Recruiting
    • Centre Georges François Leclerc
    • Contact: François GHIRINGHELLI, MD, PhD
  • Paris, France
    • Recruiting
    • Institut Gustave Roussy
    • Contact: Laurence Albiges, MD, PhD
    • Sub-Investigator: Lisa Derosa, Md, PhD
  • Strasbourg, France
    • Recruiting
    • ICANS - Institut de Cancérologie Strasbourg
    • Contact: Philippe Barthelemy, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2 - NSCLC; Oncobax-AK (1 capsule) will be administered daily until PD< excessive toxicity or withdrawal of consent	Other: Live Bacterial Product - Akkermansia muciniphila; Oral administration of Oncobax-AK to patients deficient in Akkermansia by stool metagenomic analysis.
Experimental: Phase 2 -RCC; Oncobax-AK (1 capsule) will be administered daily until PD< excessive toxicity or withdrawal of consent	Other: Live Bacterial Product - Akkermansia muciniphila; Oral administration of Oncobax-AK to patients deficient in Akkermansia by stool metagenomic analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	iRECIST	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	iRECIST	9 months

Collaborators and Investigators

• Sponsor: EverImmune
• Investigators: Principal Investigator: Fabrice Barlesi, MD, PhD, Gustave Roussy, Cancer Campus, Grand Paris

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: May 9, 2023
• First Posted (Actual): May 19, 2023

Study Record Updates

• Last Update Posted (Actual): May 19, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Kidney Neoplasms; Lung Neoplasms; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma
• Other Study ID Numbers: EV-2101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No