The INVINCIBLE study; testing INT230-6 in early-stage, presurgical breast cancer patients
Following receipt of the authorization from Health Canada, Intensity executed agreements with The Ottawa Hospital and The Ontario Institute for Cancer Research (OICR) to conduct a Phase II Randomized Trial for Intratumoral INT230-6 (VINblastine CIsplatin) Evaluating Clinical and BioLogical Effects in early Stage Breast Cancer (the INVINCIBLE trial). The study has been initiated and being conducted in two parts. The first portion is a dose ranging, preliminary evaluation of immune activation and safety with enrollment now complete. We expect to enroll a total of about 90 patients in the study.
After diagnosis with early breast cancer, women often wait 3 to 5 weeks prior to their surgery. In The INVINCIBLE s study INT230-6 is being compared to the standard of care, which is no treatment for this early stage of breast cancer or to a sham intratumoral injection of saline. There are a number of objectives for the trial; to estimate the proportion of patients who achieve a complete pathologic response on surgical specimen pathology and to measure the reduction in the proportion of cells staining positive for Ki67 (a widely used marker of cancer cell proliferation). In addition, we plan to measure the Residual Cancer Burden after treatment with INT230-6 and understand the potential for clinical benefit when using the drug prior to surgery.
The percentage of change in pathological complete response (pCR or the absence of cancer in a tumor prior to resection) has been recognized by FDA as a surrogate endpoint to support accelerated approval for neoadjuvant treatment of high-risk, early-stage breast cancer. The data from the INVINCIBLE study will help us to determine whether to proceed with a study evaluating whether the addition of INT230-6 to an existing or modified neoadjuvant (presurgical) treatment regimen may increase pCR and help to reduce toxicities in neoadjuvant triple negative breast cancer patients.
Conducting Phase 2 expansion cohorts in metastatic cancers in partnership with Merck and Bristol Myers Squibb
In 2019, the Company executed a clinical collaboration agreement with Merck Sharpe & Dohme (Merck) to evaluate the combination of INT230-6, Intensity’s lead product candidate, and KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy, in patients with advanced solid malignancies (pancreatic, colon, bile duct and squamous cell carcinoma). In 2020, the Company executed a clinical collaboration agreement with Bristol Myers Squibb (BMS) to evaluate the combination of the Company’s lead product, INT230-6, with BMS’s anti-CTLA-4 antibody, Yervoy® (ipilimumab), in patients with advanced sarcoma, breast, and liver cancers. The cohorts are open to enrollment. Information can be found at www.clinicaltrials.gov us ID number 03058289.
Completed Phase 1 portion of INT230-6 in basket study of metastatic cancers
In recent years preliminary safety and response data from patients treated during the phase 1 escalation portion of our phase 1 / 2 study in refractory metastatic patients with different solid tumors who received INT230-6 alone, and subjects who received INT230-6 combined with Keytruda® (pembrolizumab) in the phase 1 portion of our trial have been reported at major medical meetings. These include the annual American Society of Clinical Oncology (ASCO) conference and the annual Society for Immunotherapy of Cancer (SITC) conference. Please view our results on the Presentations page.
Several highly refractory patients, whose cancer has progressed following multiple drug treatments, have shown disease stabilization for more than 6 months and overall survival for patients treated with INT230-6 has been much longer than would be expected based on historical publications from similar patient populations. Further, exploratory analysis indicates that receiving intratumoral INT230-6 where the total drug volume (mL) administered over 5 sessions is equivalent or greater than approximately 40% of the patient’s total tumor burden (cc) leads to a further increase in survival compared to historical data.
INT230-6 dosing is determined based on tumor size either longest diameter or the total calculated volume based on 3 dimensions from a scan. The observation made in mouse models that a specific drug dose per volume of tumor is needed to completely saturate the injected tumors appears to be highly relevant in humans. Following treatment, many subjects’ tumors increase in size over baseline, then regress on subsequent scans. Several patients showed some size reduction of one or more non injected lesions in lymph nodes, liver, lung, perineum, and retroperitoneal areas (abscopal effects to visceral lesions). Our drug has been well tolerated, with most adverse events being of low grade (1 or 2).