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

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05865730
• Other study ID #: EV-2101
• Status: Recruiting
• Phase: Phase 2
• Start date: October 1, 2022
• Est. completion date: June 2026

Study information

• Verified date: May 2023
• Source: EverImmune
• Contact: Alain Thibault, MD
• Phone: +32472196345
• Email: alain.thibault[@]everimmune.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 122
• Est. completion date: June 2026
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Other:
• Live Bacterial Product - Akkermansia muciniphila
Oral administration of Oncobax-AK to patients deficient in Akkermansia by stool metagenomic analysis.

Locations

Country	Name	City	State
Belgium	CHU Ambroise Paré	Mons
France	Centre Georges Francois Leclerc	Dijon
France	Institut Gustave Roussy	Paris
France	ICANS - Institut de cancérologie Strasbourg	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
EverImmune

Countries where clinical trial is conducted

Belgium,  France, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	iRECIST	9 months
Secondary	Progression-free survival	iRECIST	9 months