Inclusion Criteria:
1. Provision of signed and dated informed consent form.
2. Age ≥12 years at time of informed consent.
3. Histologically proven, advanced high-grade osteosarcoma not suitable for local treatments with curative intent
4. Confirmed disease progression by radiological report to at least one line of standard chemotherapy containing cisplatin and anthracycline, and no more than 2 previous lines.
5. Measurable disease as per RECIST v1.1 criteria and documented by CT/MRI (Appendix 1 - RECIST Response Criteria). NOTE: Lesions to be used as measurable disease for the purpose of response assessment must either:
1. not reside in a field that has been subjected to prior radiotherapy, or
2. have demonstrated clear evidence of radiographic progression since the completion of prior radiotherapy and prior to study enrolment.
6. Provision of a newly obtained tumour biopsy (either from the primary tumour or from metastases) during screening and on-treatment from all patients \>16 years of age. Notes:
* The identified lesion to be biopsied should not have been previously irradiated and should not be the only lesion being used as a measurable-disease target lesion for objective response assessment. Patients must have tumour lesions that can be accessible for biopsy with acceptable clinical risk in the judgement of the Investigator.
* In case a patient has had a tumour biopsy in the previous 6 months and a paraffin block is available, a new biopsy does not need to be done at Screening (if they have received no treatment after biopsy).
7. Documented progression on or following the last line of therapy.
8. ECOG performance status 0-2 (Appendix 2 - Performance Status Criteria).
9. Life expectancy of ≥ 12 weeks as estimated by the treating physician.
10. Resolution of all acute, reversible toxic effects of prior therapy or surgical procedure to Grade ≤1 (except alopecia and peripheral neuropathy to Grade ≤2).
11. Adequate organ function.
12. If not postmenopausal or surgically sterile, female patients and female sexual partners of male patients must be willing to use at least one highly effective method of birth control (hormonal contraception, IUD, abstinence, condom) for at least a menstrual cycle before and for 3 months after last study drug administration.
Exclusion Criteria:
1. Treatment with systemic anti-cancer therapy within three weeks prior to study drug administration for chemotherapy and 5 half-lives for targeted therapies.
2. Radiation therapy within four weeks prior to study entry. Localised palliative radiotherapy to nontarget lesions is allowed
3. Low-grade osteosarcoma, parosteal, or periosteal osteosarcoma.
4. Prior history of other malignancies other than osteosarcoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 2 years.
5. Non-malignant systemic disease including cerebrovascular accident, unstable angina pectoris, unstable atrial fibrillation, unstable cardiac arrhythmia, myocardial infarction in the last six months, New York Heart Association (NYHA) Class III or IV heart failure (Appendix 5 - New York Heart Association Criteria).
6. Patients with active uncontrolled infection or known to be serologically positive for human immunodeficiency virus (HIV), hepatitis B (except after vaccination) or hepatitis C infection. Investigators may test as per their discretion.
7. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
8. Patients with symptomatic or unstable central nervous system primary tumour or metastases and/or sarcomatous meningitis
9. Live vaccine in the last four weeks.
10. Current participation in another interventional therapeutic trial.
11. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
12. Knowledge of any other disease or medication that may interfere with study treatment.
13. Patients with known allergies or hypersensitivity reactions to the active substance or to any of its excipients
14. Patient unable to comply with the study protocol owing to psychological, social (lack of social support or social exclusion) or geographical reasons.
