In this video, Dr. Michael Y. Choi, MD, Clinical Instructor, in the School of Health Sciences at University of California San Diego (UCSD) and a practicing clinician on the staff of the UCSD Moores Cancer Center is interviewed by CLL Society, founder and Chief Medical Officer, Dr. Brian Koffman, MDCM, MS ED, a retired family physician and a CLL patient. This video was recorded at the 61st Annual Meeting of the American Society of Hematology, in 2019, in Orlando, Florida.
In this interview, Dr. Choi discusses updates contained in an abstract he presented at ASH 2019 entitled: Cirmtuzumab, a ROR1 Targeted Mab, Reverses Cancer Stemness and Its Combination with Ibrutinib is Safe and Effective: Planned Analysis of the CirII Phase 1/2 trial for CLL and MCL.
Cirmtuzumab (UC-961) is a monoclonal antibody that targets the proliferation pathway of receptor tyrosine kinase-like orphan receptor 1 (ROR1). ROR1, initially identified by Dr. Thomas Kipps, MD (also at UCSD), is over-expressed on the surface of cancer cells (certain leukemias and solid tumors) but only minimally expressed on the surface of healthy cells. ROR1 is also known as neurotrophic tyrosine kinase, receptor-related 1 (NTRKR1) which is normally expressed during embryonic development but becomes dormant. For reasons that remain unknown, this protein shows back up on the surface of certain cancers. Because ROR1 is not found on healthy cells this makes it a good target for drug therapy.
- Cirmtuzumab is the first drug developed specifically for the ROR1 pathway. This antibody binds to ROR1 and the current thinking is that this turns off ROR1 by causing it to migrate from the surface of the cancer cell to the interior. This migration shuts off the cell proliferation signaling associated with ROR1.
- Dr. Choi is the primary investigator on the clinical trial that combines cirmtuzumab and ibrutinib. The Phase I portion of this clinical trial enrolled approximately 40 patients, which is standard in this level trial. Phase I trials are always about safety first and start with low doses of the trial drug and escalate to help researchers determine the recommended Phase II dose, which means finding the lowest dose with the least toxicities.
- Very early results, among this very small sample are encouraging in that they are not seeing new toxicities beyond those associated with ibrutinib monotherapy. The efficacy signals are good and appear to provide both prompt and durable responses. Among this small group of patients, there have been three complete responses (CR), after 12-months of treatment, which is far in excess of percentage of complete responses found with ibrutinib alone that almost never achieves CR as a single agent. The hope is that this combination may provide complete remission with no added toxicity.
The Phase I trial results are exciting and promising.
Phase II studies involving larger numbers of patients are coming.
The exciting aspect of this clinical trial is that if successful in larger numbers of patients in Phase II and Phase III studies, it gives CLL providers one more option to deal with the variability of patient’s disease and response to various therapies. Further, since ROR1 is not a currently approved target, the options for drugs to address refractory or relapsed CLL may expand if these trials result in product approval.
The link to find out where this clinical trial is available and more information is: https://clinicaltrials.gov/ct2/show/NCT03088878
To learn more about clinical trials, in general, go to https://cllsociety.org/clinical-trials
The original abstract for this Phase I/II study can be found at: https://doi.org/10.1182/blood-2019-131498
Thanks for reading and viewing this interview.
Stay strong, we are all in this together!
Thomas. E. Henry III, MBA, RPh, CPh