Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcoma and Osteosarcoma

Inclusion Criteria:

1. Patients must provide written informed consent prior to performance of anystudy-specific procedures and must be willing to comply with treatment and follow-up.Informed consent must be obtained prior to start of the screening process. Proceduresconducted as part of the patient's routine clinical management (e.g. imaging tests),obtained prior to signature of informed consent may be used for screening or baselinepurposes as long as these procedures are conducted as specified in the protocol.
2. Age: 18-80 years
3. Histologic diagnosis of soft tissue sarcoma (undifferentiated pleomorphic sarcoma,leiomyosarcoma, alveolar soft part sarcoma) or osteosarcoma confirmed by centralpathology review prior to enrolment with an archive tumor sample. A fresh paraffinembedded tumor tissue block must be provided for all subjects for biomarker analysisbefore and (when feasible) after treatment with investigational products.
4. Metastatic/advanced disease in progression in the last 6 months.
5. Patients have previously received at least one previous line of systemic therapy
6. Measurable disease according to RECIST 1.1 criteria.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
8. Adequate hepatic, renal, cardiac, and hematologic function.
9. Laboratory tests as follows:

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine ≤ 1.5 mg/dL

10. Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan.
11. Females of childbearing potential must have a negative serum or urine pregnancy testwithin 72 hours prior to enrollment and agree to use birth control measures duringstudy treatment and for 3 months after its completion. Patients must not be pregnantor nursing at study entry. Women/men of reproductive potential must have agreed to usean effective contraceptive method.

Exclusion Criteria:

1. Three or more previous lines of chemotherapy
2. Prior selinexor or another XPO1 inhibitor treatment.
3. Administration of a previous gemcitabine-containing treatment.
4. Any concurrent medical condition or disease (e.g. uncontrolled active hypertension,uncontrolled active diabetes, active systemic infection, etc.) that is likely tointerfere with study procedures.
5. Uncontrolled active infection requiring parenteral antibiotics, antivirals, orantifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylacticantibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
6. Pregnant or breastfeeding females.
7. Body surface area (BSA) <1.4 m2 at baseline, calculated by the Du Bois(31) orosteller(32) method.
8. Life expectancy of less than 3 months.
9. Major surgery within 4 weeks prior to C1D1.
10. Any active gastrointestinal dysfunction interfering with the patient's ability toswallow tablets, or dysfunction that could interfere with absorption of studytreatment.
11. Inability or unwillingness to take supportive medications such as anti-nausea andanti-anorexia agents as recommended by the NCCN CPGO for antiemesis andanorexia/cachexia (palliative care).
12. Any active, serious psychiatric, medical, or other conditions/situations that, in theopinion of the Investigator, could interfere with treatment, compliance, or theability to give informed consent.
13. Presence of brain or central nervous system metastases, unless they are controlled (patients with treated and stable metastasis are eligible).