According to the results at the 2022 Annual Meeting of Connective Tissue Oncology Society (CTOS), intratumoral injection therapy INT230-6 demonstrates its mechanism of dual antitumor activity as a monotherapy or in combination with Yervoy for patients with metastatic sarcoma.
As part of the open-label phase 1/2 IT-01 study, INT230-6 showed its ability to target cancer cells directly and elicit an immune anti-tumor response in soft tissue sarcoma (STS) when injected into the tumor. Treatment was well tolerated, with more than 95% of the active agent remaining in the tumor relative to intravenous administration.
Preliminary data show that when used as a monotherapy or in combination with the immune checkpoint blocker iplimma, INT230-6 can directly kill tumors in STS and trigger an anti-cancer immune response in the injected tumor.
INT230-6 is a novel therapy composed of cisplatin and vinblastine that can be injected into tumors and spread to surrounding cancer cells. In an INVINCIBLE study in breast cancer patients, it showed evidence of increased tumor necrosis and tumor infiltration of lymphocytes in . The
IT-01 trial recruited patients with advanced solid tumors including sarcoma and breast cancer in the INT230-6 monotherapy cohort, as well as patients with breast cancer, hepatocellular carcinoma and sarcoma who received INT230-6 plus Iprimma. The data presented reported 15 patients with sarcoma who received monotherapy and 14 patients with sarcoma who received combination of iplimma. The demographic data of the selected patients were similar whether they received monotherapy or combination therapy: the median previous treatments in the single-therapy treatment group were 3, while the median previous treatments in the combination therapy group was 4. Most patients had ECOG performance score of 1.
primary endpoint is the incidence and severity of (TRAE) associated with grade 3 or higher treatment-related adverse events (TRAE) up to 5 years. Secondary endpoints include initial control or regression of tumor size and several key pharmacokinetic parameters, and overall survival (OS) is an exploratory endpoint.
Scan of chordoma injected with INT230-6 monotherapy showed that the volume decreased from 55.65 mm × 32.48 mm to 47.5 mm × 18.78 mm at 6 months, which was considered a partial response. As we all know, the components of INT230-6, cisplatin and vinblastine, have immune activation effects. On day 28 after 2 doses of INT230-6 treatment, the researchers observed activation of CD3, CD4, and CD8 T cells in tumors in 2 selected patients (one with ovarian cancer and another with liposarcoma).
Although there was no control group for this study, the researchers compared the overall survival (OS) results with other phase 1/2 studies in sarcoma patients and concluded that the median OS for the control group was 205 days. The median OS for patients receiving INT230-6 monotherapy was 649 days. Of the 15 patients who received a cumulative dose exceeding 40% of their total tumor burden, 11 patients had a median OS of 715 days. Median OS was not achieved in the INT230-6 plus Iprimma group at 345 days of median follow-up. Twelve of the 14 patients were still alive at the time of data cutoff.
For TRAE in the INT230-6 monotherapy group, there was a 3-grade incidence of local tumor-related pain, fatigue, anemia, and hyponatremia . Local tumor-associated pain is common at any level TRAE, which occurs in 12 patients (80.0%), followed by nausea in 6 patients (40.0%) and fatigue in 5 patients (33.3%). There was 1 treatment-related incidence of grade 3 anemia in the INT230-6 plus Iprimma group. Common TRAEs of any grade were local tumor-associated pain in 6 patients (42.9%), fatigue in 5 patients (35.7%), and nausea in 4 patients (28.6%) No grade 4 or 5 TRAE was reported in either group.
Based on the safety and early efficacy demonstrated in this trial, a randomized phase 3 trial is planned to study the efficacy of the drug. Compared with standard chemotherapy, INT230-6 can show clinical benefits and lower levels of off-target side effects. The proposed Phase 3 trial, which is scheduled to begin in 2023, will include patients with locally advanced or metastatic STS who have received line 1 or 2 treatment.Up to 332 patients will be randomly assigned to INT230-6 or standard treatment in a 2:1 ratio, which may be pazopanib (Votrient), trabetidine (Yondelis), or Halaven. The primary endpoint is OS, and the secondary endpoints include safety and quality of life.
