Clinical trial NCT05865730: A Study of Oncobax®-AK in Patients With Advanced Solid Tumors
Official title: A Phase 1/2 Study of Oncobax®-AK Administered in Combination With Immunotherapy To Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Carcinoma, Renal Cell
Carcinoma, Non-Small-Cell Lung
Lead sponsor: EverImmune
Sponsor class: INDUSTRY
First posted: 2023-05-19
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1 cohort of patients with NSCLC recruited in parallel to 1 cohort recruiting RCC patients.
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Objective Response Rate
timeFrame: 9 months
Secondary outcomes:
measure: Progression-free survival
timeFrame: 9 months
Other outcomes:
Locations:
city: Mons
country: Belgium
facility: CHU Ambroise Paré
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Paris
country: France
facility: Institut Gustave Roussy
city: Strasbourg
country: France
facility: ICANS - Institut de cancérologie Strasbourg
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Fabrice Barlesi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.