Howard S. Hochster, MD: [00:00:00] Um,
first of all, this is for late line colorectal cancer after the standard chemotherapy and targeted therapy drugs. it’s a space where we’re seeing new drugs approved for colon cancer, but many people continue to have the need for additional treatments once they finish the approved drugs. this particular drug is quite novel, ME344.
we are working, in the, AGIC group, the Academic GI Cancer Consortiwhich is an academically based Phase II national consortium. with MEI Pharma to test this drug. It’s novel because it interrupts mitochondr m my this is novel because it, interferes with mitochondrial oxidative phosphorylation and can cause cell death on a totally [00:01:00] different mechanism.
We also have some data from breast cancer trials in the past that an anti VEGF, especially Bevacizumab, can potentiate the activity of this agent. So the trial is ongoing. We are accruing patients. quite, regularly and we’re looking for an end point of, four month progression free survival as a, Simon early stopping rule and we’re not quite at that level where we can decide if we’ll continue forward with the trial or not.
The drug is quite well tolerated with very few side effects and, certainly, there are a number of patients that have had stable disease on the treatment to date.
OncologyTube: Excellent. How does the mechanism of action of ME344, specifically inhibiting Oxfos, complement the effects of anti [00:02:00] angiogenetics, like Bevacizumab, in the treatment of refractory metastatic colorectal cancer?
Howard S. Hochster, MD: Well, this, the question as to, why we believe that there’ll be more activity of an anti angiogenic with, an Oxfos inhibitor is a good one, and I think it’s more empirical based on preclinical data and one breast cancer trial, but we believe that, by inhibiting the energy source in tumor cells at the same time, improving The vascularity of the tumors that will get a larger effect.
OncologyTube: Okay, can you explain the rationale behind enrolling patients who have already failed standard therapies, including various chemotherapy regimens and targeted therapies in this Phase 1B study with MA344 and Bevacizumab?
Howard S. Hochster, MD: the question as to the right way to develop new drugs in colon cancer remains a challenge, [00:03:00] but in this case, I think the paradigm that has been most successful recently is in the space of late line colon cancer.
After patients have received the standard chemotherapy drugs of a fluoroperimidine, oxaliplatin, arenotecan, and the appropriate, and targeted therapies, usually an anti VEGF drug and an, and or an anti EGF receptor drug. So, we have a number of drugs approved in that space now, regorafenib, TASC 102 and, fruquentinib and we think that this is where an ongoing need to treat, colon cancer patients exists at this time.
What
OncologyTube: are the primary and secondary endpoints of this Open Label Phase 1B study and how do they measure the safety and efficacy of ME344 in combination with bevacizumab The
Howard S. Hochster, MD: primary endpoint of this study will be a [00:04:00] progression free survival at 16 weeks or 4 months. that’s the time that people are getting their second, scan evaluation at that time.
And we’re looking for at least disease stabilization or response at that time point. That’s kind of an early indicator if the drug is showing sufficient activity or not, and then if we continue to enroll after that up to 50 patients, we’ll look at the response rate and progression free survival for this combination.
OncologyTube: Okay, for our GI oncologists at home, what are the key takeaways from this study so far?
Howard S. Hochster, MD: this is a study in late line colon cancer looking at a, an agent with a novel mechanism of cell killing for cancer cells, by inhibiting mitochondrial oxidative phosphorylation. We’re combining it with, an anti angiogenic to improve its activity.
And we hope to see, whether this will be worth, continuing further development [00:05:00] if it shows sufficient activity in this late line setting.
OncologyTube: Alright, this has been an interview with Dr. Howard Hoekstra, Medical Doctor, Associate Director for Clinical Research, and Director, GI Oncology, Rutgers Cancer Institute, and Distinguished Professor of Medicine, Dr.
Hoekstra. Thank you so much for sitting down with us.
Howard S. Hochster, MD: Thank you.