INT230-6 demonstrated direct tumor killing in soft tissue sarcoma and elicits an anti-cancer immune response within the injected tumor both alone and in combination with ipilimumab.
INT230-6 demonstrated direct tumor killing in soft tissue sarcoma (STS) and elicits an anti-cancer immune response within the injected tumor both alone and in combination with ipilimumab (Yervoy), according to findings from the single-arm, phase 1/2, open-label Study IT-01 (NCT03058289).
In results from 29 heavily pretreated patients with different metastatic sarcomas who received intratumoral INT230-6 as monotherapy (n = 15) or with ipilimumab (n = 14), investigators found that the median overall survival (OS) was not reached for those assigned to the combination at 345 days median follow-up. There have been only 2 deaths reported in this group as of data cutoff.
For those who received a cumulative dose of INT230-6 greater than 40% of their total tumor burden, the median OS was 715 days (95% CI, 649-1352). The median OS for all patients was 649 days (95% CI, 195-1352). The median OS was 205 days for the synthetic control group.
“The compelling safety and efficacy results from use of our drug in treating such a deadly and hard-to-treat cancer as soft tissue sarcomas underscore the potential of this treatment. The promising data support our belief that INT230-6 could show clinical benefit with lower levels of off-target side effects compared with standard chemotherapies,” Lewis H. Bender, president and CEO of Intensity Therapeutics, said in a news release. “We have designed a randomized phase 3 trial protocol to evaluate INT230-6 versus standard of care in patients with advanced soft tissue sarcomas and look forward to initiation of the study.”
INT230-6 combines cisplatin, vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. INT230-6 induces direct killing of the tumor by releasing a bolus of neoantigens specific to the patient’s malignancy, which results in systemic antitumor effects without the immunosuppression associated with systemic chemotherapy.
Patients in the monotherapy arm received a median of 3 prior therapies (range, 0-8) compared with 4 (range, 0-9) in the combination arm. In phase 2 of the study, patients were assigned to a maximum dose of 175 mL INT230-6 administered every 14 days for up to 5 doses. Those with breast cancer, sarcoma, or hepatocellular carcinoma received 4 doses of ipilimumab every 3 weeks.
The sarcoma subtypes between the 2 arms comprised sacral chordoma (n = 7), liposarcoma (n = 4), pleomorphic sarcoma (n = 3), chondrosarcoma (n = 1), Kaposi’s sarcoma (n = 1), leiomyosarcoma (n = 5), myofibroblastic (n = 1), osteosarcoma (n = 1), osteosarcoma (n = 1), chordoma (n = 2), spindle cell sarcoma (n = 2), fibrosarcoma (n = 1), and Langerhan sarcoma (n = 1).
Patients with squamous cell carcinoma or pancreatic, microsatellite stable colon, or bile duct cancers were assigned to INT230-6 plus pembrolizumab (Keytruda) every 3 weeks for 2 years. Those data will be released at a later date.
Patients received 266 total injections, 158 (59.3%) of which went into deep visceral tumors. The primary outcome measure was safety. Secondary end points included median OS, disease control rate (DCR), and pharmacokinetic profile.
The median age was 64 years (range, 42-76) in the monotherapy arm and 63 years (range, 33-82) in the combination arm. Eleven patients in the monotherapy arm were male while the combination arm was evenly balanced.
Fourteen (93.3%) patients in the monotherapy arm experienced any-grade treatment-related adverse events (TRAEs). However, there were no grade 4 AEs and only 3 patients experienced grade 3 events. The most common any-grade TRAE was localized tumor-related pain (n = 12; 80.0%).
Twelve (85.7%) patients in the combination arm experienced any-grade TRAEs, with 1 grade 3 AE of anemia (7.1%). The most common grade 1/2 TRAE was localized tumor-related pain (n = 6; 42.9%).
Investigators plan to initiate a randomized phase 3 study of INT230-6 in patients with soft tissue sarcoma in 2023.