A study to investigate efficacy and safety of INT230-6 compared with US standard of care in participants aged ≥ 18 years old with metastatic soft tissue sarcomas

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intensity Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Nov 2024 → ongoing

Decision date (initial)

2024-09-17

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Intensity Therapeutics, Inc.

External identifiers

EU CT number

2024-512423-36-00

ClinicalTrials.gov

NCT06263231

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare OS for INT230-6 vs US SOC in participants with unresectable or metastatic liposarcoma, undifferentiated pleomorphic sarcoma or leiomyosarcoma

Secondary objectives 5

1. To compare OS for INT230-6 vs US SOC in participants with leiomyosarcoma
2. To compare OS for INT230-6 vs US SOC in participants with liposarcoma
3. Exploratory: To compare the incidence of grade 3 or higher drug-related AEs of INT230-6 vs US SOC in participants with aSTS
4. Exploratory: To compare the QoL using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) questionnaire of INT230-6 vs US SOC in participants with aSTS
5. Exploratory: Compare health parameters

Conditions and MedDRA coding

Undifferentiated pleomorphic sarcoma

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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; legal representatives are not allowed)
2. Histologically proven, unresectable, locally advanced, or metastatic 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 aSTS 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 CT or MRI.
6. Participant must have an ECOG performance status of 0, 1 or 2
7. Participant must have adequate organ function as defined by screening laboratory values that must meet the following criteria: a. Neutrophils ≥ 1500/μL (≥ 1.5× 1000000000/L). b. PT, and INR ≤ 1.5× ULN, platelets ≥ 100,000/μL (≥ 10× 1000000000/L); hemoglobin ≥ 9 g/dL. Criteria must be met without erythropoietin dependency and without packed red blood cell transfusion within the last 2 weeks. c. Creatinine within normal range; or calculated creatinine clearance > 50 mL/min by the Cockcroft-Gault equation. d. ALT SGOT/ AST SGPT ≤ 2.5× ULN without, and ≤ 5× ULN with hepatic metastases. e. Bilirubin ≤ 1.5× ULN (except participants with Gilbert’s syndrome, who must have total bilirubin < 3.0 mg/dL [< 52 μmol/L]). f. Creatine phosphokinase < 2.5× ULN
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: a. Not a 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 FSH and estradiol will be obtained to confirm childbearing potential. b. 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
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
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 ICF and in this protocol.

Exclusion criteria 20

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 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. Use of other investigational drugs (drugs not marketed for any indication) must be discontinued at least 28 days prior to study intervention administration.
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 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.
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 1 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 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.
20. Pregnancy Exclusion: A WOCBP who has a positive serum pregnancy test at the clinical visit, prior to treatment. If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS), as defined as the time from date of randomization to date of death due to any cause.

Secondary endpoints 7

1. OS as defined as the time from date of randomization to date of death due to any cause.
2. Exploratory: The incidence of grade 3 or higher drug-related AEs will be assessed by the incidence of > grade 3 drug-related AEs according to the CTCAE (v6.0).
3. Exploratory: Change from baseline in the global health status/QoL scale score of the EORTC QLQC30 (Time Frame: Up to 24 months).
4. Exploratory: Summary of composite measure of change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment.
5. Exploratory: Time to 10% definitive deterioration in the global health status/QOL scale score of the EORTC QLQ-C30 (Time Frame: Up to 24 months).
6. Exploratory: Definitive deterioration: time from date of randomization to date of event, defined as at least a 10% worsening from baseline with no later improvement above this threshold observed during the course of the treatment or until death due to any cause, in the global health status/QOL scale score of EORTC QLQ-C30.
7. Exploratory: Changes in safety parameters including laboratory test results, ECOG performance status, etc.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intensity Therapeutics Inc.

Sponsor organisation

Intensity Therapeutics Inc.

Address

1 Enterprise Drive Suite 430

City

Shelton

Postcode

06484-4779

Country

United States

Scientific contact point

Organisation

Intensity Therapeutics Inc.

Contact name

Zubair

Public contact point

Organisation

Intensity Therapeutics Inc.

Contact name

Zubair

Third parties 4

Locations

5 EU/EEA countries · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 3 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 36 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications