Use in Metastatic Disease – Phase 3
Given the positive data on survival seen in our metastatic study in sarcoma patients, we plan to conduct a single Phase 3 study in 2nd/3rd line treatment for locally advanced, recurrent, inoperable, or metastatic non-diffuse soft tissue sarcoma with overall survival as the primary endpoint. The current Phase 3 study design plans to enroll subjects who will be randomized 2 to 1 to either INT230-6 for 5 doses every weeks with maintenance dosing every 9 weeks for 2 years or the standard of care. The three drugs most used for soft tissue sarcoma will be the control SOC at the investigator’s choice depending on the type of sarcoma. Our Phase 3 study is designed to be 90% powered to detect a difference Hazard Value of 0.65 in overall survival between the INT230-6 treatment group and the control group with 331 patients enrolled (2:1 randomization to either INT230-6 treatment or control therapy). The study will have 2 interim data reviews to determine efficacy. The first interim analysis is planned when 50% of the required events (deaths) for the final analysis has occurred and the second analysis will be at 75%. Futility will also be tested as part of the interim analysis. A protocol synopsis was developed and submitted to the FDA. On October 14, 2021, we met with FDA to discuss the Phase 3 protocol and reached alignment on the Phase 3 study design, patient population and statistical approach.
The U.S. Food and Drug Administration has granted INT230-6 Fast Track Designation and reviewed Company’s development program to investigate INT230-6 for the treatment of patients with relapsed or metastatic triple negative breast cancer who have failed at least 2 prior lines of therapy. Intensity has designed a Phase 2/3 program for INT230-6 for Metastatic Breast Cancer. Should resources become available we could initiate this program.
Presurgical (neoadjuvant) use – Phase 3
The results from the INVINCIBLE study indicate that INT230-6 can cause >95% of a large tumor to become necrotic on a single dose without toxicity other than minor pain at the injection site. Combining one or two doses upfront of INT230-6 with the standard of care neoadjuvant therapy (pembrolizumab with anthracycline, cyclophosphamide and taxane) could potentially increase the pCR rate to allow for an FDA accelerated approval. The data on percent tumor necrosis from the INVINCIBLE study indicate that meaningful necrosis can be induced prior to conventional neoadjuvant treatment. Follow receipt of the final data from the INVINCIBLE study, we plan to request another meeting with FDA to review a phase 2/3 randomized trial program in neoadjuvant breast cancer with pCR improvement for an accelerated approval endpoint to be followed with a full approval based on event free survival.