A Multicenter, Randomized, Phase 3 Study to Assess the Efficacy and Safety of INtratumorally Administered INT230-6 (SHAO, VINblastine, CIsplatin) Compared With US Standard of Care in Adults With Locally Recurrent, InoperaBLE, or Metastatic Soft Tissue Sarcomas (INVINCIBLE-3)
To compare Overall Survival (OS) for INT230-6 vs United States (US) Standard of Care (SOC) in participants with unresectable or metastatic liposarcoma, undifferentiated pleomorphic sarcoma or leiomyosarcoma who have disease progression prior to study enrollment following no more than 2 standard therapies, which must have included an anthracycline-based regimen, unless contraindicated, and then a maximum of 1 additional regimen.
• Participant is of any sex and must be ≥ 18 years old and provide written informed consent to participate in the study.
• Type of Participant and Disease Characteristics
• Histologically proven, unresectable, locally advanced, or metastatic Soft Tissue Sarcoma (STS) only of the following subtypes: liposarcoma (dedifferentiated, myxoid, round cell or pleomorphic), leiomyosarcoma, and undifferentiated pleomorphic sarcoma. Participant must have a pathology report indicating the diagnosis of their STS.
• Participant must have received at least 1 line of therapy for a STS and must have progressed following anthracycline-based or alternative standard therapies, except if medically contraindicated or refused by participant. Participant cannot have received more than 2 prior regiments for unresectable, locally advanced or metastatic STS.
• Participant must have measurable disease per RECIST 1.1 criteria.
• Participant must have at least 1 target tumor suitable for injection using routine image guidance ≥ 2 cm measurable by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI).
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (see Section 11.7).
• Participant must have adequate organ function as defined by screening laboratory values that must meet the following criteria:
‣ Neutrophils ≥ 1500/μL (≥ 1.5× 109/L).
⁃ Prothrombin Time (PT), and International Normalized Ratio (INR) ≤ 1.5× Upper Limit of Normal (ULN), platelets ≥ 100,000/μL (≥ 10× 109/L); hemoglobin ≥ 9 g/dL. Criteria must be met without erythropoietin dependency and without packed red blood cell transfusion within the last 2 weeks.
⁃ Creatinine within normal range; or calculated creatinine clearance \> 50 mL/min by the Cockcroft-Gault equation.
⁃ Alanine Aminotransferase (ALT) Serum Glutamic-Oxaloacetic Transaminase (SGOT)/ Aspartate Aminotransferase (AST) Serum Glutamic-Pyruvic Transaminase (SGPT) ≤ 2.5× ULN without, and ≤ 5× ULN with hepatic metastases.
⁃ Bilirubin ≤ 1.5× ULN (except participants with Gilbert's syndrome, who must have total bilirubin \< 3.0 mg/dL \[\< 52 µmol/L\]).
⁃ Creatine phosphokinase \< 2.5× ULN Sex and Contraceptive/Barrier Requirements
• A female participant is eligible to participate if she is not pregnant (as demonstrated by pregnancy testing prior to each treatment; performed at least monthly), not breastfeeding, and at least 1 of the following conditions applies:
‣ Not a Woman of Childbearing Potential (WOCBP). Women of non-childbearing potential are defined as women with functioning ovaries with a documented history of tubal ligation or hysterectomy or females who are post menopausal, as defined by 12 months of spontaneous amenorrhea with an appropriate clinical profile, e.g., age appropriate, \> 45 years, in the absence of hormone replacement therapy. In questionable cases, a blood sample for Follicle Stimulating Hormone (FSH) and estradiol will be obtained to confirm childbearing potential.
⁃ A WOCBP who may become pregnant or who is sexually active with a partner and who could become pregnant agrees to use a highly effective form of contraception during the study and for at least 7 months after the end of study intervention (see Section 11.5.2 for highly effective methods of contraception).
• Male participants with female partners of childbearing potential must agree to use contraception and refrain from sperm donation during the study and for 6 months after the end of study intervention (Section 11.5.2.2).