Data Monitoring Committee OKs INVINCIBLE-3 Sarcoma Trial Continuation

The phase 3 INVINCIBLE-3 trial is evaluating INT230-6 vs standard of care in locally recurrent, inoperable, or metastatic soft tissue sarcoma.

A data monitoring committee has authorized the continuation of the phase 3 INVINCIBLE-3 trial (NCT06263231) evaluating INT230-6, composed of cisplatin and vinblastine sulfate, vs standard of care (SOC) as a treatment for patients with locally recurrent, inoperable, or metastatic soft tissue sarcoma (STS), according to a news release from the drug’s developer, Intensity Therapeutics.1

The data monitoring committee reviewed data covering July to December 2024. Additionally, authorizations for the phase 3 trial have been obtained from the FDA, Health Canada, the European Medicines Agency, and Australia’s Therapeutic Goods Administration.

"The data monitoring committee is designed to confidentially review data to determine whether safety concerns with the data collected to date exist,” Lewis H. Bender, MS, MA, MBA, president and chief executive officer of Intensity Therapeutics, said in the news release.1 “We are encouraged by the continuation of the trial and continue to believe that INT230-6 represents important potential in a treatment area that has significantly unmet medical need. We look forward to continuing enrollment and to providing further updates as they develop."

The open-label, controlled study phase 3 trial is assessing the safety and efficacy of INT230-6 given intratumorally by a trained physician vs systemically dosed SOC chemotherapy, consisting of either pazopanib (Votrient) tablets, trabectedin (Yondelis), or eribulin mesylate (Halaven).

Patients treated with INT230-6 will receive a dose every 2 weeks ± 2 days totaling 5 treatment sessions.2 Once the treatment phase has concluded, a 22-month maintenance phase begins, wherein investigators may inject new or previously treated lesions with a maximum of INT230-6 every 12 weeks ± 14 days, with dose volume dependent on tumor volume.

Patients treated in a comparator arm are given either 800 mg of pazopanib tablets every day until disease progression or clinical deterioration, 1.5 mg/m2 of intravenous trabectedin every 3 weeks until disease progression or clinical deterioration, or 1.4 mg/m2 intravenous eribulin on days 1 and 8 of every 3-week cycle until disease progression or clinical deterioration in non-European Union (EU) sites. In EU sites, eribulin dosing is reduced to 1.23 mg/m2.

The study is seeking to screen approximately 333 adult patients with STS who experienced disease progression with prior study regimens, which must have included an anthracycline-based regimen unless contraindicated. Patients are permitted to have received 1 additional regimen. Following screening, patients are randomly assigned to receive either INT230-6 or a SOC regimen.

No crossover is permitted between study arms. Disease progression will be determined by World Health Organization (WHO) criteria. Furthermore, patients will be stratified by histologically defined STS strata, which include leiomyosarcoma; dedifferentiated, myxoid, round cell, and pleomorphic liposarcoma; and undifferentiated pleomorphic sarcoma.

The primary study end point is overall survival (OS). Secondary end points include OS in leiomyosarcoma and liposarcoma, and safety.

INT230-6 was previously assessed in a phase 2 trial (NCT03058289) as monotherapy or with ipilimumab (Yervoy), the results of which were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.3 Results from the trial showed that the median OS for INT230-6 alone was 649 days. The median OS was 715 days for patients who received a dose at a volume to total tumor burden ratio of 40% or greater.

The maximum tolerated INT230-6 dose was 175 mL, including 87.5 mg of cisplatin and 17.5 mg of vinblastine sulfate, in 1 or more tumors, which exceeds intravenous dosing with either singular therapy. Additionally, grade 3 treatment-related adverse events (TRAEs) occurred in 20% of patients treated with INT230-6 alone, with no grade 4 or 5 AEs observed.

References

1. Drug monitoring committee authorizes continuation of Intensity Therapeutics' ongoing global randomized phase 3 sarcoma trial ("INVINCIBLE-3 Study") following periodic review. News release. Intensity Therapeutics. January 28, 2025. Accessed January 28, 2025. https://tinyurl.com/359cj4ju
2. A study to investigate efficacy & safety of intratumoral INT230-6 compared to US standard of care in adults with soft tissue sarcomas (INVINCIBLE-3) (INVINCIBLE-3). ClinicalTrials.gov. Updated January 9, 2025. Accessed January 28, 2025. https://tinyurl.com/44w9k43h
3. Meyer CF, Ingham M, Hu JS, et al. Intratumoral INT230-6 (cisplatin, vinblastine, shao) alone or with ipilimumab prolonged survival with favorable safety in adults with refractory sarcomas. J Clin Oncol. 2025;41(suppl 16):11568. doi:10.1200/JCO.2023.41.16_suppl.11568