REPLATINUM Phase III  - Why does it matter? -Tony Reid, MD
What is The Phase III REPLATINUM Clinical Trial In Small Cell Lung Cancer (SCLC)?
Interesting question, RRx-001 was tested in the phase III REPLATINUM clinical trial. Is it a new compound, and what has it been used for? So the answer to that is, absolutely, it is a new compound. There is nothing else like it. It is a traditional alkylating agent. But then, on alkylating cystines, not DNA protein cystines, it converts to a biologic agent and actually releases nitric oxide.
As you were asking, the thing that's probably most similar to it would be nitroglycerin. But it has a strange ring structure. So when it binds to cystine, it releases nitric oxide. And similar to nitroglycerine, which alters the vascular microenvironment, this alters the tumor (cell) microenvironment.
And so we're very excited about it. It is a completely new molecule and, in fact, has its own stem. It's a bromo nitro, there is no other molecule like it.
What Is The Current Standard of Care In Patients with Small Cell Lung Cancer (SCLC)?
I'm a practicing doctor of clinical oncology and treating patients with small cell lung cancer, a very devastating and not a stable disease. And one of the things that's really attractive to me about this is its lack of toxicity. It does not bind to DNA outplates, proteins, or emit nitric oxide. We don't really have the same kind of toxicity to the bone marrow as we do to other organs. So, very interesting in small cell lung cancer.
Initially, the upfront treatment is usually a platinum and atopic side with or without a checkpoint inhibitor or an immune therapy. And patients usually respond pretty well to that. You can have a big regression, which is good for a medical oncologist because most patients feel better when that happens.
But one of the true conundrums in the field is that it tends to come back very rapidly. So even though you get a very good initial response, 6 to 8 to 9 months later, the small cell lung cancer comes back very aggressively (with a poor prognosis) and at that point it's usually resistant to any further chemotherapy, hindering superior progression free survival (overall survival).
So second line therapy is usually another chemotherapy agent like Topotecan with or without a checkpoint inhibitor, and complete response rates to that are relatively low. We placed this in third-line therapy. They're mostly third-line therapies, which is more chemotherapy, which is largely ineffective and very toxic.
And so we felt that with our mechanism of action, cystine alkylation release of nitric oxide altering the tumor microenvironment to change immunosuppressive macrophages into immunostimulatory, we had a real chance to make a big difference there. And to do so with limited toxicity.
What Was The REPLATINUM Phase III Clinical Trial Design For Small Cell Lung Cancer?
So, the REPLATINUM clinical trial design really derives from what we were talking about before in first and second line therapy. The patients had to go through first and second line therapy, so they would've had to have a platinum agent and have two lines of therapy.
And it's designed really to give an effective therapy, hopefully one with much less toxicity. Our main goals are how long it takes for the disease to get worse and how long people live in general. Quality of life and managing symptoms are the main goals of our secondary goals.
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What Led You To Study Small Cell Lung Cancer?
Yeah, that's funny. When I was an undergraduate, I had no prior exposure to medicine. I had no interest in medicine. And, it was in the days when I needed a work study job. And it was in the days of the 3x5 card and the cork board.
And I remember standing there, and the only job really available was taking care of rats in a cancer research facility, and I was somewhat deflated by that. I never really thought of taking care of rats or getting involved with cancer research. But when I got there, it was truly amazing. and I started out taking care of the rats for them, and soon I was helping them with their experiments. And soon I was doing their experiments.
And then, pretty soon, the chairman of the department came by and asked me what my goals and intentions were. And I ended up applying to an MD PhD program. I got accepted, and I've been doing cancer research and cancer therapy ever since, running a laboratory and patients treatment and really hoping to make a difference.
Final Thoughts On RRx-001
I think the critical thing about EpicentRx is that we're focused on novel agents. We have two platforms; one is the small molecule RRx-001, and the other one is the AdAPT platform, which is a gene therapy platform.
And the critical thing here for Rxo1 is that it's really a very novel agent. There's really nothing else like it. It is made when an alkylating agent links cystines to a biological agent that releases nitric oxide in the tumor microenvironment. and alters that tumor microenvironment in ways that make it directly effective as small cell lung cancer therapy.
But I think the upside potential is amazing. We really have an opportunity to us them in combination this with other therapies. We're very excited about a partnership with Cyclone, which is a company in China, as everyone knows. Small cell lung cancer is very prevalent in Asian countries, so we're excited about a collaboration with them to bring this forward, not only in the US but worldwide.
Tony Reid, MD, PhD - About The Author, Credentials, and Affiliations
Dr. Tony Reid is the CEO of EpicentRx. He has a Ph.D. from Stanford University in Antiviral and Antitumor Activity. Reid went to Stanford to get his medical degree in clinical oncology. He focused on targeted viral vectors for cancer therapies and histone deacetylase inhibitors.
In addition to his job at EpicentRx, Dr. Reid continues his 13-year tenure as a medical oncologist at the University of California San Diego Moores Cancer Center as a professor of medicine, specializing in early-phase clinical research while simultaneously creating an adenoviral platform.
Dr. Reid is the recipient of multiple national honors, including America's Top Doctor (top 1%) from 2008 to the present), America's Top Doctor for Cancer (top 1% from 2009 to the present), and America's Most Honored Professional (top 1% from 2016 to the present).