Study of Orellanine in Metastatic Clear-Cell or Papillary Renal Cell Carcinoma

Inclusion criteria:

1. Has provided written informed consent.

2. Has a diagnosis of histologically confirmed advanced ccRCC or pRCC. No conventionaltherapy is available or considered appropriate by the treating physician or isdeclined by the patient.

3. For patients in the expansion portion of the study only: Measurable disease perRECIST version 1.1 criteria.

4. ECOG performance status of 0 - 2.

5. Age ≥18 years.

6. Life expectancy ≥3 months.

7. Has acceptable haematologic laboratory values defined as:

8. Neutrophils ≥1.5 × 10^9/L, without growth factor stimulation within 3 weeksprior to the blood test;

9. Platelets ≥100 × 10^9/L;

10. Haemoglobin ≥5.6 mmol/L (~90 g/L). Use of erythropoietin or blood transfusionsare permitted.

11. Has acceptable liver laboratory values defined as:

12. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN for patients with liver metastases

13. Total bilirubin ≤1.5 × ULN or direct bilirubin ≤ ULN for patients with totalbilirubin levels >1.5 × ULN

14. For patients diagnosed with Gilbert's syndrome, total bilirubin ≤2 × ULN isacceptable.

15. Must be on chronic hemodialysis (on a consistent regimen for the previous threemonths, with allowance for intermittent treatments as required for volume overload).

16. The patient's treating nephrologist and oncologist agree that the prospect of lossof remaining renal function resulting from this treatment will not significantlychange the patient's future and chronic dialysis treatment.

17. Female patients of child-bearing potential and male patients must agree to use 2forms of highly effective contraception for the duration of study treatment andafter the last dose of orellanine for at least 3 months for males and 6 months forfemales.

18. For females of child-bearing potential, a negative serum pregnancy test atscreening.

19. Patients who are willing and able to comply with travel requirements, scheduledvisits, treatment schedule, efficacy assessments, laboratory tests, and other studyprocedures.

Exclusion criteria:

1. Diagnosis of any other malignancy within 2 years prior to enrolment, except foradequately treated basal cell or squamous cell skin cancer, superficial melanoma, orcarcinoma in situ of the breast or of the cervix, or low grade (Gleason 7 or below)prostate cancer on surveillance with no plans for treatment intervention (e.g.,surgery, radiation, or castration)

2. Radiotherapy within 2 weeks before first dose.

3. Immuno-oncology therapy (IO) given in the last six (6) months prior to enrolment

4. Other systemic anti-cancer therapy within 2 weeks before first dose.

5. Has not recovered from AEs due to prior anti-cancer medications to at least grade 1by CTCAE version 5.0 (except for alopecia and grade 2 neuropathy).

6. Has received any other investigational product within 4 weeks before first dose.

7. Pregnant or breastfeeding women.

8. Uncontrolled medical condition including, but not limited to, ongoing or activeinfection or psychiatric illness/social situations that would limit compliance withstudy requirements, or would, in the opinion of the investigator, place the patientat increased risk.

9. QTc interval at baseline of ≥470 msec.