Treatment With Dinutuximab Beta, Zoledronic Acid and Low-dose Interleukin (IL-2) in Patients With Leiomyosarcoma

Inclusion Criteria:

1. Patients must have histologically confirmed leiomyosarcoma.

2. ≥ 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy (anthracycline-containing regimen).

3. Patients must have a cryopreserved and formalin-fixed paraffin-embedded tumor sampleavailable for submission to central pathology review.

4. Signed Written Informed Consent.

5. Men and women aged ≥ 18 years.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

7. Measurable disease.

8. Locally advanced/unresectable or metastatic disease.

9. No prior therapy with any agent targeting GD2.

10. Confirmed GD2-Expression proven on cryopreserved tissue tumor samples. A stainingscore of 2 on cryopreserved tissue is sufficient for enrollment of the patient.

11. No treatment with biologic therapy, immunotherapy, chemotherapy, investigationalagent for malignancy, or radiation ≤ 21 days before study registration.

12. No participation in another clinical trial in the period 30 days prior to start offirst dose.

13. Patients should have resolution of any toxic effects of prior therapy (exceptalopecia) to NCI CTCAE, version 5.0, grade 1 or less.

14. Not pregnant and not nursing; for women of childbearing potential who are sexuallyactive, a negative pregnancy test (urinary or serum beta-HCG) done ≤ 7 days prior totreatment start is required.

15. Absolute neutrophil count (ANC) ≥ 1,000/mm3.

16. Platelet count ≥ 70,000/mm3.

17. Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinineclearance > 45 mL/min.

18. Total bilirubin ≤ 1,5 x upper limit of normal (ULN). If total bilirubin is greaterthan 1,5 x ULN, measure indirect bilirubin to evaluate for Gilbert's syndrome (ifdirect bilirubin is within normal range, participant may be eligible).

19. AST/ALT ≤ 2.5 x upper limit of normal (ULN).

20. Adequate pulmonary function (FEV1 > 2 liters or ≥ 75% of predicted for height andage).

21. No clinical significant heart failure (NYHA<III) or ejection fraction (echocardiography or scintigraphy; EF > 40%)

22. Female participants must be postmenopausal (no spontaneous menses for at least 2years), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tuballigation, or otherwise be incapable of pregnancy), abstinent (at the discretion ofthe investigator), or if sexually active, have agreed to use an highly effectivecontraceptive method for the duration of their study participation (see Appendix 3for guidance); patients should maintain adequate contraception for a minimum of 2months after the last dose of dinutuximab beta. Male participants must agree to usean adequate contraception method as deemed appropriate by the investigator (e.g.,vasectomy, double-barrier, partner using effective contraception) and to not donatesperm for a minimum of 5 months after treatment discontinuation.

Exclusion Criteria:

1. Symptomatic, untreated, or uncontrolled brain metastases present.

2. Patients with a known history of hypersensitivity to interleukin-2.

3. Patients with a hypersensitivity to zoledronic acid or to other bisphosphonates.

4. Need for invasive dental procedures. Preventive dental exams should be performedbefore starting zoledronic acid.

5. Patients after allogenic stem cell transplantation or other allogenic organtransplantation (e.g., liver, kidney etc.).

6. Patients with different malignant diseases other than sarcoma (measurablemanifestations in the last 12 months or active therapy against the other malignantdisease in the last 12 months).

7. Known active pulmonary disease with hypoxia defined as:

• Oxygen saturation < 85% on room air or

• Oxygen saturation < 88% despite supplemental oxygen.

8. Uncontrolled intercurrent illness including, but not limited to, poorly controlledhypertension or diabetes, ongoing active infection, or psychiatric illness/socialsituation that may potentially impair the participant's compliance with studyprocedures.

9. Patients who have received prior anti-GD2 therapy, including chimeric antigenreceptor (CAR) T cells directed against GD2 antigen.

10. Lactating females are not eligible unless they have agreed not to breastfeed theirinfants.

11. Any condition that, in the opinion of the investigator, would compromise thewell-being of the participant or the study or prevent the participant from meetingor performing study requirements.