The INVINCIBLE study tested INT230-6 in early-stage, presurgical breast cancer patients. Patients had strong interest in the drug; recruitment was rapid
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 was conducted in two parts both of which are now complete. The first portion was dose ranging. Key objectives were to understand safety of 1, 2 or 3 doses of INT230-6 compared to the standard of care, which is no treatment. The second part compared INT230-6 to saline solution intratumoral injections. The key objectives were to understand the percent necrosis from a single dose and effect on various biomarkers.
The overall goals of the study (both parts) were to understand changes in cancer proliferation, gene activation and immune response in the tumor and blood. A total of 91 patients were enrolled. Patients were randomized to either INT230-6 (60), no treatment (9) or saline injection (20). Two patients were excluded.
In The INVINCIBLE we seek to determine whether patients could achieve a complete pathologic response or a major pathological reduction of their surgical specimen and nodes using INT230-6 alone. These important pathology measures are correlated with the prevention of disease recurrence. We also seek to measure the reduction in the proportion of cells staining positive for Ki67 (a marker of cancer cell proliferation for systemic drug therapy). In addition, we wish to understand the potential for clinical benefit of INT230-6 when using the drug prior to surgery in the current neoadjuvant settings.
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 helped us to determine that the addition of INT230-6 to an existing or modified neoadjuvant (presurgical) treatment regimen may improve the pCR rate when added to the current presurgical standard of care for triple negative patients (TNBC). Our drug has the potential to reduce toxicities in these TBNC patients as well. We are planning to return to FDA with a phase 3 registration trial design and plan.
Conducted Phase 2 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. There were 110 patients having 25 different cancers treated in the study. Sixty-four (64) patients received INT230-6 alone. Thirty (30) received a combination of INT230-6 with Keytruda and 18 patients were treated using a combination of INT230-6 with Yervoy. Information can be found at www.clinicaltrials.gov us ID number 03058289.
Completed both the Phase 1 and Phase 2 portions of study IT-01 with treatment in 25 different metastatic cancer types
We have reported safety, immune response and efficacy data from patients treated during the escalation and phase 2 portions of our study in refractory metastatic patients at major cancer meetings. The selection committees from the world’s most important oncology conferences’ have chosen our data for oral podium discussion by independent key opinion leaders. These medical conferences include the annual American Society of Clinical Oncology (ASCO) conference, the annual Society for Immunotherapy of Cancer (SITC) conference, the annual Connective Tissue Oncology Society (CTOS, which is for sarcoma) and the annual San Antonio Breast Cancer Symposium (SABCS). Please view our presentation and results on the Presentations page.
In our metastatic study IT-01, a high percentage of highly refractory patients treated with INT230-6, whose cancer had progressed following multiple drug treatments – a median of 3 and primarily all approved therapies – have shown disease stabilization. There has also been a significant increase in overall survival compared to expected for this severely ill population. 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 baseline incoming total tumor burden (measured in cubic centimeters from scans) leads to a further increase in survival compared to historical data.
INT230-6 dosing is determined from scan data. The to-be-injected dose is based by either the tumor longest diameter (for tumors under 9 cm) or the total calculated volume based on 3 dimensions using the modified ellipsoid formula. 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 mild or moderate i.e. low grade (1 or 2) based on CTCAE scoring.