A PHASE 1/2 STUDY OF ONCOBAX®-AK ADMINISTERED IN COMBINATION WITH IMMUNOTHERAPY TO PATIENTS WITH ADVANCED SOLID TUMORS

Prior treatment

• Immunosuppressive therapy (>10 mg prednisone/day equivalent) within 4 weeks of signed informed consent.
• Radiotherapy (>30 Gy) to the lung(s) within 6 months of signed informed consent.

Other illness

• Active inflammatory bowel disease and/or any medical condition that alters the integrity of the intestinal barrier.
• Auto-immune diseases requiring systemic therapy.
• Known allergy to Oncobax®-AK excipients.
• Active infection. A 4-week delay must have elapsed between the resolution of any systemic infection and the initiation of Oncobax®-AK administration.

Lab values

• Alanine aminotransferase (ALT) >5 times the upper limit of normal range (ULN).
• Calculated creatinine clearance <40 mL/min.

Other

• 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.
• Pregnancy or breast-feeding.
• Other co-morbidities that, in the opinion of the Investigator, may place the patient at a higher risk of treatment-related AEs.
• Inability to comply with protocol-specific assessments.
• Patient is subject to any of the following procedures: ward of court, trusteeship, supervision order, applied mandate of future protection.
• Vaccination with a live attenuated virus, other than influenza, within 6 months of signed informed consent.

• Histologically or cytologically confirmed Stage IV NSCLC (for Phase 2 only) or clear cell RCC.
• Hemoglobin ≥90 g/L.
• Neutrophil count ≥1.0 x 10^9/L.
• Platelet count ≥75 x 10^9/L.
• Lymphocyte count > 0.5 x 10e^9/L.
• Albumin >30 g/L.
• A wash-out period of 5 half-lives or more since the last dose administered of any investigational medicinal products or chemotherapy received previously.
• 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).
• Signed informed consent form.
• Patient eligible for SOC PD-L1 based immunotherapy or chemo-immunotherapy (for NSCLC, for Phase 2 only) and ipilimumab + nivolumab (for RCC)).
• 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.
• RCC cohort-specific criterion: intermediate- or poor-risk newly diagnosed RCC patients (clear cell histology).
• 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.
• NSCLC cohort-specific criterion (for Phase 2 only): PD-L1 expression data ≥ 1%.
• At least one measurable (target) lesion per iRECIST.
• Eastern Cooperative Oncology Group (ECOG) performance status = 0-1.
• Age >18 years.