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

Sarcoma,Soft Tissue Clinical Trial

— INVINCIBLE-3  

Official title:

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06263231
• Other study ID #: IT-03
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: December 2028

Study information

• Verified date: February 2024
• Source: Intensity Therapeutics, Inc.
• Contact: Kimberly Guedes, RN, M.B.A
• Phone: (203) 293-4224
• Email: KGuedes[@]intensitytherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 333
• Est. completion date: December 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Participant is of any sex and must be = 18 years old and provide written informed consent to participate in the study, or consent may be provided by the participant's legally acceptable representative (In Germany: participants must be able to provide consent to participation.) 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 (non-uterine), 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 180 days 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 90 days after the end of study intervention (Section 11.5.2.2). Informed Consent

10. Participant (or legally acceptable representative if applicable) is capable of giving signed informed consent and provides written informed consent for the study as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol. Exclusion Criteria:

Medical Conditions:

1. Prior primary or metastatic brain or meningeal tumors unless clinically and radiographically stable as well as off-steroid therapy for at least 2 months.

2. History of severe hypersensitivity reactions to US SOC agents and vinblastine or cisplatin or other products of the same class and their excipients.

3. 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.

4. 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.

5. 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).

6. 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.

7. Participants who require uninterrupted anticoagulants of any type or is on daily aspirin therapy or NSAIDS.

8. 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).

9. 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.

10. 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.

11. 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.

12. Participants actively receiving therapy with strong Cytochrome P450 3A4 isoenzyme (CYP3A4) inhibitors (e.g, erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil).

13. 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

14. 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.

15. 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.

16. Use of other investigational drugs (drugs not marketed for any indication) within 28 days prior to study intervention administration.

17. Received a live vaccine within 6 weeks of first dose of study intervention.

18. 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

19. 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.

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma,Soft Tissue

Intervention

Drug:
• INT230-6
INT230-6 is a fixed combination of cisplatin, vinblastine and SHAO.
• Eribulin
Eribulin IV
• Trabectedin
Trabectedin infusion
• Pazopanib
Pazopanib pill

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Intensity Therapeutics, Inc.	Premier Research Group plc

References & Publications (21)

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	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	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	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.