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

NCT06263231 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: IT-03
• Study Type: interventional
• Target: 333
• Locations: 5 countries
• Sites: 17

Brief Summary

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.

Conditions

Sarcoma,Soft Tissue

Outcome Measures

Primary Outcomes (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.

  From date of randomization until the documented date of death from any cause for a period of up to 2 years, unless superiority is demonstrated sooner or 80% of deaths during the study period.

Secondary Outcomes (2)

• Overall Survival (OS) For INT230-6 Compared to OS for Standard of Care (SOC) for Participants with leiomyosarcoma

  From date of randomization until the documented date of death from any cause for a period of up to 2 years, unless superiority is demonstrated sooner or 80% of deaths during the study period.

• Overall Survival (OS) For INT230-6 Compared to OS for Standard of Care (SOC) for Participants with liposarcoma

  From date of randomization until the documented date of death from any cause for a period of up to 2 years, unless superiority is demonstrated sooner or 80% of deaths during the study period.

Study Arms (2)

INT230-6 Monotherapy

EXPERIMENTAL

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

US Standard of Care

ACTIVE COMPARATOR

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; Drug: Trabectedin; Drug: Pazopanib

Interventions

INT230-6 DRUG

INT230-6 is a fixed combination of cisplatin, vinblastine and SHAO.

INT230-6 Monotherapy

Eribulin DRUG

Eribulin IV

US Standard of Care

Trabectedin DRUG

Trabectedin infusion

US Standard of Care

Pazopanib DRUG

Pazopanib pill

US Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• Informed Consent:
• Adult participants who lack capacity to consent without a legally authorized representative will be excluded from this study.
• Medical Conditions:
• Prior primary or metastatic brain or meningeal tumors unless clinically and radiographically stable as well as off-steroid therapy for at least 2 months.
• History of severe hypersensitivity reactions to US SOC agents and vinblastine or cisplatin or other products of the same class and their excipients.
• 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.
• 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.
• 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).
• 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.
• Participants who require uninterrupted anticoagulants of any type or is on daily aspirin therapy or NSAIDS.
• 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).
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Intensity Therapeutics, Inc.: lead
• Premier Research: collaborator

Study Sites (17)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

University of California Los Angeles (UCLA) - Santa Monica Cancer Care

Santa Monica, California, 90404, United States

Location

Yale School of Medicine - Smilow Cancer Hospital - Yale - New Haven Hospital Location

New Haven, Connecticut, 06519, United States

Location

Profound Research LLC

Farmington Hills, Michigan, 48333, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania - Abramson Cancer Center

Philadelphia, Pennsylvania, 19106, United States

Location

Temple University - Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Leon Berard

Lyon, 69008, France

Location

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Universitäres Krebszentrum (UCCL)

Leipzig, 04103, Germany

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitari Vall Hebron

Barcelona, 08740, Spain

Location

Centro Integral Oncologico Clara Campal (HM CIOCC)

Madrid, 28050, Spain

Location

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MeSH Terms

Conditions

Sarcoma

Interventions

eribulin; Trabectedin; pazopanib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Christian F. Meyer, MD, PhD, MS

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 16, 2024
• Study Start: June 28, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: During the study for a period of 4 years.

Locations

ES (3); FR (1); US (10); DE (2); CA (1)