INT230-6 Shows Promising Efficacy, Safety in Sarcomas

Soft tissue sarcoma

INT230-6, a locally derived cytotoxic treatment, led to improvements in overall survival (OS) and disease control rate (DCR) alone and in combination with ipilimumab (Yervoy) in patients with relapsed, refractory, and metastatic sarcomas, according to results from the phase 1/2 IT-01 (NCT03058289) trialpresented at the Connective Tissue Oncology Society (CTOS) Annual Meeting 2023 in Dublin, Ireland.¹

The median OS of patients treated with INT230-6 was 14.9 months compared with 6.8 months in patients treated with a synthetic control. The DCR was 93% in patients who received at least 1 dose of INT230-6 as monotherapy.²

"The data presented at CTOS highlights the true potential of INT230-6 as both a monotherapy or in combination with ipilimumab. INT230-6 showed an extensive increase in overall survival in [patients with metastatic sarcomas] over expected results for the heavily pretreated and diverse sarcoma population with an increase of nearly 15 months compared to a synthetic control. Approval of INT230-6, a locally delivered therapy, could be a paradigm-changing treatment for metastatic cancers," said Lewis H. Bender, president and chief executive officer of Intensity Therapeutics, INT230-6’s manufacturer, in a press release.¹

About IT-01

Fifteen patients were enrolled in the INT230-6 monotherapy arm, and 14 patients were enrolled in the INT230-6/ipilimumab combination arm. The median age in the monotherapy arm was 64 years (range, 42-76), and 73.3% of patients were male. The median age in the combination arm was 63 (range, 33-82), and 50% of patients were male. The median number of prior therapies in the monotherapy arm was 3 (range, 0-8), and the median was 4 (range, 0-9) in the combination arm.²

Along with the primary end points of OS and DCR, the study’s secondary end points include safety and pharmacokinetics.¹

Patients in the monotherapy arm received INT230-6 injections every 28 days for 5 cycles with a low starting dose and low concentration per tumor or injections, or every 2 weeks with a higher starting dose and moderate drug concentration per tumor. In the ipilimumab combination arm, patients received INT230-6 every 2 weeks at the higher dose and concentration for 5 cycles with ipilimumab every 3 weeks for 4 treatments.³

"INT230-6 can fully saturate a tumor with cytotoxic agents to begin apoptosis and cause necrosis when delivered intratumorally, resulting in immune activation consisting of dendritic and T-cell influx to the tumor all while maintaining a favorable safety profile,” Bender added.

Safety Profile of INT230-6

For safety, 90% of adverse events (AEs) observed in the trial were grade 1 or 2. In the monotherapy arm, 107 AEs were observed, while 76 AEs were observed in the combination arm. In the monotherapy arm, 12 patients (80%) experienced localized tumor-related pain, 6 patients (40%) experienced nausea, 5 patients experienced fatigue (33.3%), 3 patients (20%) experienced vomiting, 4 patients (26.7%) experienced decreased appetite, and 3 patients (20%) experienced anemia.

In the combination arm, 6 patients (42.9%) experienced localized tumor-related pain, 5 patients (35.7%) experienced fatigue, 4 patients (28.6%) experienced nausea, 3 patients (21.4%) experienced vomiting, 2 patients (14.3%) experienced decreased appetite, 2 patients (14.3%) experienced anemia, 3 patients (21.4%) experienced pruritus, and 3 patients (21.4%) experienced maculopapular rash.

One patient in the combination arm and 2 patients in the monotherapy arm experienced grade 3 AEs. There were no grade 4 or 5 AEs.²

Future of INT230-6

Investigators are designing a phase 3 study to compare INT230-6 as a monotherapy with standard-of-care pazopanib (Votrient), trabectedin (Yondelis), and eribulin (Halaven). Up to 332 patients will be randomized in a 2:1 fashion. The primary end point will be OS, and secondary end points will be safety, quality of life, OS for leiomyosarcoma, and OS for liposarcoma.

REFERENCES:

1. Intensity Therapeutics presents positive INT230-6 data in patients with refractory tissue sarcoma at the Connective Tissue Oncology Society Annual Meeting 2023. News release. Intensity Therapeutics. November 2, 2023. Accessed November 2, 2023. https://tinyurl.com/mumxun6v

2. Meyer C, Ingham M, et al. Intratumoral INT230-6 (cisplatin, vinblastine, shao) alone or with ipilimumab prolonged survival with favorable safety and immune activation in adults with refractory sarcomas (NCT03058289). Presented at: Connective Tissue Oncology Society Annual Meeting 2023; November 1-4, 2023; Dublin, Ireland. Abstract 1574238.

3. A phase 1/2 safety study of intratumorally dosed INT230-6 (IT-01). ClinicalTrials.gov. Updated March 2, 2023. Accessed November 2, 2023. https://clinicaltrials.gov/study/NCT03058289