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.
After diagnosis, women often wait 4 weeks prior to their surgery. INT230-6 is being compared to the standard of care, which is no treatment for this early stage of breast cancer. 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.
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
Preliminary safety and response data from 53 subjects with different solid tumors who received monotherapy (INT230-6 alone), and 7 subjects who received INT230-6 combined with Keytruda® (pembrolizumab) in the phase 1 portion of our trial were reported at the Society for Immunotherapy of Cancer 2020 annual meeting. Several highly refractory patients have had disease stabilization for more than 6 months.
INT230-6 dosing is determined based on tumor size. A minimum threshold of dose per volume needed to saturate tumors as seen in nonclinical models appears to be relevant in humans. Analysis of dose response relationship is ongoing; however, results show that receiving INT230-6 doses equivalent to half of the tumor burden (for tumors above 2 cm in diameter) results in an increase in survival. Data presented show doses >50% compared to <50% provide a survival with a Hazard Ratio of 0.272 (95% CI: 0.125, 0.592) (p=0.00103).
Following treatment, many subjects’ tumors increase in size over baseline, then regress on subsequent scans (potential pseudo progression). 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). The drug was well tolerated, with most adverse events being of low grade (1 or 2). Over 25% of patients receiving an INT230-6 dose of greater than 50% of their incoming tumor burden had an un-injected tumor regress, an abscopal effect.