Our Colorectal Cancer Program
Metastatic colorectal cancer that has become refractory to two lines of chemotherapy and is not responsive to first generation checkpoint inhibition or CAR-T cell immunotherapy is the lead indication for our next generation immunotherapy. The US FDA has approved two drugs for third-line metastatic colorectal cancer patients: regorafenib (Stivarga®) and TAS-102 (Lonsurf®).
In a randomized, controlled clinical trial of 760 third-line metastatic colorectal cancer patients randomized 2:1 with regorafenib vs. best supportive care, the overall survival was 6.4 months for regorafenib compared to 5.0 months for best supportive care (1.4 months survival advantage). In double-blind, randomized, placebo-controlled Phase III study of 800 third-line metastatic cancer patients assigned 2:1 to receive TAS-102 or placebo, the overall survival in the placebo group of 5.3 months was improved to 7.1 months with TAS-102 (1.8 months survival advantage). These studies provide a good historical control for third-line metastatic colorectal cancer patients demonstrating a median life expectancy of 5.0 to 5.3 months.
In our Phase IIA 3+3 dose and dose frequency finding clinical trial in patients with the same third-line metastatic colorectal cancer inclusion/exclusion criteria as the regorafenib and TAS-102 trials, the median overall survival was 9.6 months. In the best triplicate, the overall survival was 11.6 months (over double the survival of historical controls). We are currently attempting to confirm the survival signal in the best triplicate in an open-label Phase IIB multi-center clinical trial. See ClinicalTrials.gov Identifier: NCT04444622.
Our colorectal cancer program is our developed country initiative, as the incidence and mortality of colorectal cancer is highest in developed countries. (our liver cancer program is targeted to less developed countries). Colorectal cancer is the third most common cancer diagnosed in both men and women in the United States. The American Cancer Society's estimates for the number of colorectal cancer cases in the United States for 2020 are: 147,950 new cases. In 2017, there were an estimated 1,348,087 people living with colorectal cancer in the United States.
Estimated US New Cases in 2020 147,950
% of All New US Cancer Cases 8.2%
Estimated US Deaths in 2020 53,200
% of All US Cancer Deaths 8.8%
USA Colorectal Cancer Incidence
Our colorectal cancer program initially targets USA patients suffering from disease that has already spread to distant sites referred to as metastatic (stage IV) colorectal cancer.
Cure is not currently possible for most patients with metastatic colorectal cancer. Chemotherapy is the option most commonly used for prolonging life of patients with metastatic colorectal cancer. Sometimes both chemotherapy and surgery are recommended.
Patients normally receive at least two different lines of chemotherapy regimens for treatment of metastatic disease. When patients can no longer tolerate or progress after two lines of chemotherapy, they become eligible for our experimental immunotherapy.
Immunotherapy has only shown activity against colorectal cancer in a subset (about 10%) of patients that have a type of colorectal cancer termed microsatellite high (MSI-H). The latest research has shown that certain checkpoint inhibitors, called PD-1 or PD-L1 inhibitors, can be effective against metastatic colorectal cancer that is MSI-H. However, the majority of colorectal cancers are not MSI-H, but are rather microsatellite stable (MSI-S). These MSI-S patients generally do not respond to immunotherapy.
Our next generation immunotherapy is designed to provide benefit to the MSI-S metastatic colorectal cancer population that are no longer responding to chemotherapy. In our Phase IIA clinical study in this population, the best treatment schedule tested provided double the survival expected based on historical controls. Significantly, the extended survival was provided without causing deterioration of the quality of life.
Our Phase IIB clinical study, now cleared by US FDA, is designed to expand these findings and determine if the survival data observed can be repeated in a larger population.
Upon completion of our USA Phase IIB open label, multi-site metastatic colorectal cancer trial in the USA, we plan to expand next to the EU.
Colorectal cancer (CRC) is the most common cancer in EU; with about 450,000 people newly diagnosed each year in Europe, approximately 4 times the incidence as in the USA.