A Study to Investigate Efficacy & Safety of Intratumoral INT230-6 Compared to US Standard of Care in Adults With Soft Tissue Sarcomas (INVINCIBLE-3)

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified June 2025 by Intensity Therapeutics, Inc.
Sponsor
Intensity Therapeutics, Inc.
Information Provided by (Responsible Party)
Intensity Therapeutics, Inc.
Clinicaltrials.gov Identifier
NCT06263231
Other Study ID Numbers:
IT-03
First Submitted
January 31, 2024
First Posted
February 15, 2024
Last Update Posted
July 28, 2025
Last Verified
June 2025

ClinicalTrials.gov processed this data on July 2025. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Sarcoma,Soft Tissue
Drug: INT230-6Drug: Eribulin

Study Design

Study TypeInterventional
Actual Enrollment333 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA 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)
Study Start DateJune 27, 2024
Actual Primary Completion Date1yr 6mos from now
Actual Study Completion Date2yrs 6mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
INT230-6 Monotherapy
INT230-6 administered intratumorally. Participants will be dosed every 2 weeks (± 2 days) for up to a total of 5 treatment sessions (e.g., Days 1, 15, 29, 43 and 57). Once the participant has completed the treatment phase, they will continue into a 22-month maintenance phase, where investigators may inject new lesions or previously injected lesions with up to 175 mL of INT230-6 every 12 weeks (Q12W) ± 14 days. Dose volume in a session is dependent on the participants presenting tumor burden.
Drug: INT230-6
INT230-6 is a fixed combination of cisplatin, vinblastine and SHAO.
US Standard of Care
Participants in this arm may receive any of the following depending on soft tissue sarcoma (STS) subtype and PI preference: * Pazopanib: 800 mg PO every day until clinical deterioration or disease progression * Trabectedin: 1.5 mg/m2 body surface area as 24-hour IV infusion every 3 weeks until clinical deterioration or disease progression * Eribulin: Non- European Union (EU) sites: 1.4 mg/m2 eribulin mesylate body surface area IV on Days 1 and 8 every 3 weeks until clinical deterioration or disease progression EU sites: 1.23 mg/m2 (free base) body surface area IV on Days 1 and 8 every 3 weeks until clinical deterioration or disease progression
Drug: Eribulin
Eribulin IV

Outcome Measures

Primary Outcome Measures
  1. Overall Survival (OS)
    To compare OS for INT230-6 vs 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.
Secondary Outcome Measures
  1. Overall Survival (OS) For INT230-6 Compared to OS for Standard of Care (SOC) for Participants with leiomyosarcoma
    To compare OS for INT230-6 vs US SOC in participants with leiomyosarcoma
  2. Overall Survival (OS) For INT230-6 Compared to OS for Standard of Care (SOC) for Participants with liposarcoma
    To compare OS for INT230-6 vs US SOC in participants with liposarcoma

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
1. 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 2. 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. 3. 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. 4. Participant must have measurable disease per RECIST 1.1 criteria. 5. 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). 6. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (see Section 11.7). 7. Participant must have adequate organ function as defined by screening laboratory values that must meet the following criteria: 1. Neutrophils ≥ 1500/μL (≥ 1.5× 109/L). 2. 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. 3. Creatinine within normal range; or calculated creatinine clearance \> 50 mL/min by the Cockcroft-Gault equation. 4. 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. 5. Bilirubin ≤ 1.5× ULN (except participants with Gilbert's syndrome, who must have total bilirubin \< 3.0 mg/dL \[\< 52 µmol/L\]). 6. Creatine phosphokinase \< 2.5× ULN Sex and Contraceptive/Barrier Requirements 8. 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: 1. 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. 2. 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). 9. 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).
Exclusion Criteria
Informed Consent: 1. Adult participants who lack capacity to consent without a legally authorized representative will be excluded from this study. Medical Conditions: 2. Prior primary or metastatic brain or meningeal tumors unless clinically and radiographically stable as well as off-steroid therapy for at least 2 months. 3. History of severe hypersensitivity reactions to US SOC agents and vinblastine or cisplatin or other products of the same class and their excipients. 4. Histologically proven, unresectable, locally advanced or metastatic STS subtypes other than those specified, for example excluded subtypes include liposarcoma (well differentiated), desmoid or dermatofibrosarcoma protuberans. 5. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or superficial bladder cancer, or any other cancer from which the participant has been disease-free for at least 2 years. 6. Underlying medical condition that, in the investigator's opinion, will make the administration of study intervention hazardous or obscure the interpretation of toxicity determination or Adverse Events (AEs). 7. Concurrent medical condition requiring the use of immunosuppressive medications, or systemic corticosteroids (topical steroids are permitted); systemic corticosteroids must be discontinued at least 4 weeks prior to dosing. Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if the participant is on a stable dose. Non-absorbed intra-articular steroid injections will be permitted. Use of steroids as prophylactic treatment for participants with contrast allergies to diagnostic imaging contrast dyes will be permitted. 8. Participants who require uninterrupted anticoagulants of any type or is on daily aspirin therapy or NSAIDS. 9. Known significant chronic liver disease, such as cirrhosis or active hepatitis (potential participants who test positive for hepatitis B surface antigen or hepatitis C antibodies are allowed provided they do not have active disease requiring antiviral therapy). 10. Myocardial infarction within 6 months before enrollment, New York Heart Association Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease or electrocardiographic evidence of acute ischemic or active conduction system abnormalities. 11. Uncontrolled intercurrent illness including, but not limited to, poorly controlled hypertension or diabetes, ongoing active infection or psychiatric illness/social situation that may potentially impair the participant's compliance with study procedures. 12. Participants with a Corrected QT interval (QTc) of \>450 ms for men and \>470 ms for women, or with a history of serum electrolyte abnormalities known to prolong the QT interval such hypocalcemia, hypokalemia, and hypomagnesemia, or a family or personal history of congenital long QT syndrome. 13. Participants actively receiving therapy with strong Cytochrome P450 3A4 isoenzyme (CYP3A4) inhibitors (e.g, erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil). 14. Participants actively receiving therapy with medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study intervention. Prior/Concomitant Therapy 15. Prior chemotherapy or immunotherapy (tumor vaccine, cytokine or growth factor given to control the cancer: systemic or IT) must have been completed at least 4 weeks prior to dosing (with the exception of kinase inhibitors or other short half-life drugs, a 2-week washout is acceptable prior to treatment) and all AEs have either returned to baseline or stabilized. Note: participants who have received prior platinum therapy are eligible irrespective of their response. If participant had received one of the 3 US SOC study regimens prior to enrollment, that previous US SOC cannot be assigned in this study. 16. Prior systemic radiation therapy (IV, intrahepatic or oral) completed at least 4 weeks prior to study intervention administration. Prior focal radiotherapy completed at least 2 weeks prior to study intervention administration. a. Prior major treatment-related surgery completed at least 4 weeks prior to study intervention administration. 17. Use of other investigational drugs (drugs not marketed for any indication) within 28 days prior to study intervention administration. 18. Received a live vaccine within 6 weeks of first dose of study intervention. 19. Received a Coronavirus Disease (COVID-19) vaccine less than 1 week prior to dosing (Cycle 1/Day 1) and/or during the study received a COVID-19 vaccine or booster less than 3 weeks ahead of a tumor assessment. Other Exclusion Criteria 20. Pregnancy Exclusion: A WOCBP who has a positive pregnancy test (e.g., within 72 hours) prior to treatment. If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Contacts and Locations

Sponsors and CollaboratorsIntensity Therapeutics, Inc.
Locations
USC/Norris Comprehensive Cancer Center | Los Angeles California, United States, 90033Sarcoma Oncology Center | Santa Monica California, United States, 90403University of California Los Angeles (UCLA) - Santa Monica Cancer Care | Santa Monica California, United States, 90404Yale School of Medicine - Smilow Cancer Hospital - Yale - New Haven Hospital Location | New Haven Connecticut, United States, 06519Profound Research LLC | Farmington Hills Michigan, United States, 48333Nebraska Methodist Hospital | Omaha Nebraska, United States, 68114Duke Cancer Center | Durham North Carolina, United States, 27710The James Cancer Hospital and Solove Research Institute | Columbus Ohio, United States, 43210University of Pennsylvania - Abramson Cancer Center | Philadelphia Pennsylvania, United States, 19106Temple University - Fox Chase Cancer Center | Philadelphia Pennsylvania, United States, 19111Princess Margaret Cancer Centre | Toronto Ontario, Canada, M5G 2M9Centre Leon Berard | Lyon , France, 69008Helios Klinikum Bad Saarow | Bad Saarow , Germany, 15526Universitäres Krebszentrum (UCCL) | Leipzig , Germany, 04103Hospital de la Santa Creu i Sant Pau | Barcelona , Spain, 08025Hospital Universitari Vall Hebron | Barcelona , Spain, 08740Centro Integral Oncologico Clara Campal (HM CIOCC) | Madrid , Spain, 28050
Investigators
Principal Investigator: Christian F. Meyer, MD, PhD, MS, Johns Hopkins University