A Phase 1/2 Study of Oncobax®-Ak Administered in Combination with Immunotherapy to Patients with Advanced Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Everimmune

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Oct 2022 → 9 Apr 2026

Decision date (initial)

2024-10-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

EverImmune SAS

External identifiers

EU CT number

2024-516711-24-00

EudraCT number

2022-000163-53

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy

Phase 1: Characterize the safety profile and tolerability of repeated doses of Oncobax®-AK, administered in combination with PD-L1-based chemo-immunotherapy in metastatic RCC patients deficient in Akkermansia
Phase 2: Characterize the efficacy of repeated doses of Oncobax®-AK administered in combination with PD-L1-based immunotherapy in metastatic NSCLC or RCC patients and deficient in Akkermansia

Secondary objectives 1

1. Phase 2: - Characterize the efficacy of repeated doses of Oncobax®-AK administered in combination with PD-L1-based immunotherapy in metastatic NSCLC or RCC patients. -Characterize the safety profile and tolerability of repeated doses of Oncobax®-AK administered in combination with PD-L1-based immunotherapy in metastatic NSCLC or RCC patients

Conditions and MedDRA coding

Non-Small Cell Lung Cancer (NSCLC), Renal Cell Carcinoma (RCC)

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Histologically or cytologically confirmed Stage IV NSCLC (for Phase 2 only) or clear cell RCC.
2. Patient eligible for SOC PD-L1 based immunotherapy or chemo-immunotherapy (for NSCLC, for Phase 2 only) and ipilimumab + nivolumab (for RCC)).
3. NSCLC cohort-specific criterion (for Phase 2 only): best tumor response (by iRECIST) as stable disease (SD) between 12 and 18 weeks after initiation of first line PD-L1-based immunotherapy or chemo-immunotherapy.
4. RCC cohort-specific criterion: intermediate- or poor-risk newly diagnosed RCC patients (clear cell histology).
5. Negative stool polymerase chain reaction (PCR) test for Akkermansia (A. muciniphila and A. massiliensis) as defined in paragraph 11.2.7.2. of the protocol.
6. NSCLC cohort-specific criterion (for Phase 2 only): PD-L1 expression data ≥ 1%.
7. At least one measurable (target) lesion per iRECIST.
8. Eastern Cooperative Oncology Group (ECOG) performance status = 0-1.
9. Age >18 years.
10. Hemoglobin ≥90 g/L.
11. Neutrophil count ≥1.0 x 10^9/L.
12. Platelet count ≥75 x 10^9/L.
13. Lymphocyte count > 0.5 x 10e^9/L.
14. Albumin >30 g/L.
15. A wash-out period of 5 half-lives or more since the last dose administered of any investigational medicinal products or chemotherapy received previously.
16. For patients of child-bearing potential, commitment to use a birth control method with a failure rate of less than 1% per year, during the entire treatment period AND for at least 4 months after the last dose of ICI (for NSCLC patients, for Phase 2 only) OR at least 5 months after the last dose of nivolumab (for RCC patients).
17. Signed informed consent form.

Exclusion criteria 14

1. Symptomatic brain metastases. Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period.
2. Alanine aminotransferase (ALT) >5 times the upper limit of normal range (ULN).
3. Calculated creatinine clearance <40 mL/min.
4. Auto-immune diseases requiring systemic therapy.
5. Immunosuppressive therapy (>10 mg prednisone/day equivalent) within 4 weeks of signed informed consent.
6. Known allergy to Oncobax®-AK excipients.
7. Radiotherapy (>30 Gy) to the lung(s) within 6 months of signed informed consent.
8. Active infection. A 4-week delay must have elapsed between the resolution of any systemic infection and the initiation of Oncobax®-AK administration.
9. Vaccination with a live attenuated virus, other than influenza, within 6 months of signed informed consent.
10. Pregnancy or breast-feeding.
11. Active inflammatory bowel disease and/or any medical condition that alters the integrity of the intestinal barrier.
12. Other co-morbidities that, in the opinion of the Investigator, may place the patient at a higher risk of treatment-related AEs.
13. Inability to comply with protocol-specific assessments.
14. Patient is subject to any of the following procedures: ward of court, trusteeship, supervision order, applied mandate of future protection.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Phase 1: - AEs, TEAEs, related TEAEs, SAEs, DLTs per NCI CTCAE version 5.0. - Dose reductions and interruptions. Phase 2: - ORR per iRECIST

Secondary endpoints 1

1. Phase 2: - PFS9, OS12, DOR. - AEs, TEAEs, related TEAEs, SAEs, DLTs, per NCI-CTCAE version 5.0. - Dose reductions and interruptions

Investigational products

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

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Everimmune

Sponsor organisation

Everimmune

Address

39 Rue Camille Desmoulins

City

Villejuif

Postcode

94800

Country

France

Scientific contact point

Organisation

Everimmune

Contact name

Alain Thibault

Public contact point

Organisation

Everimmune

Contact name

Cyrille Jeune

Third parties 1

Locations

2 EU/EEA countries · 5 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 27 files

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

Application history

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