Anti-CD47: New Therapy Advancing

A new video from Irv Weissman (Stanford) has come out that updates the status of the experimental anti-CD47 monoclonal antibody immunotherapy- it is progressing through phase 1 and they are in the planning stages for trials involving breast cancer, in this case starting with HER2-positive patients and combining the anti CD-47 with Herceptin. He shows the drug has remarkable synergy with Herceptin in mice (around the 15-16 minute mark). The approach they are planning to take is also remarkable. First, the metastatic breast cancer cells are removed from the marrow, dropping the tumor burden remarkably. They showed in trials 20 years ago that this step alone CURED about 20% of the patients! To improve on those numbers, in this trial they will restore the immune system and then treat the remaining (now much smaller number) of metastatic cancer cells with Herceptin and anti-CD47. Important to note that although the trial will be HER2-positive patients, this therapy in principle should also work well in the other subtypes of breast cancer, and indeed in most cancers, at least when added in combination with targeted therapies. Keep an eye on this area..

Here is a link to the new video:

Here are some trials that target the CD47 receptor and accept breast cancer patients.

Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides

TTI-621 (SIRPαFc) is a soluble recombinant fusion protein created by directly linking the sequences encoding the N-terminal CD47 binding domain of human SIRPα with the Fc domain of human immunoglobulin (IgG1). TTI-621 acts by binding human CD47 and preventing it from delivering an inhibitory "do not eat" (antiphagocytic) signal to macrophages.

In this trial they inject the tumor directly, so you need to be IDC with tumors they can reach. It is not out of Stanford, but has sites in Los Angeles (City of Hope) and Seattle, Pennsylvania and Oregon.

Phase 1 Trial of Hu5F9-G4, a CD47-targeting Antibody

This is the trial led by Irv Weissman's company. The sites are Stanford, Michigan and Texas. First in human, first in class. Any solid tumor will do. This is the paper that reviews the pre-clinical data that supports the trial. This trial has reported preliminary safety data and it appears to be well tolerated. I wouldn't hesitate to try it based on safety concerns, but I would prefer to have some efficacy data as well to know if it was worth betting on.

A Phase 1, Dose Finding Study of CC-90002 in Subjects With Advanced Solid and Hematologic Cancers

CC-90002-ST-001 is an open-label, Phase 1, dose escalation and expansion, first in human (FIH) clinical study of CC-90002, administered by intravenous (IV) infusion, in subjects with advanced, refractory solid and hematologic cancers.

This trial is Arizona, UCSF and San Antonio, TX. It looks like they combine it with standard of care, but it's not clear how that works with MBC. This is IV ever 28 days for a while.

The video talks about a trial done a long time ago of high dose chemo followed by stem cell recovery. This is a good article summarizing the outcomes of that trial. They are very promising, but I don't see ongoing trials.

Personally, I am holding off on immunotherapy trials until I have burned through at least the hormonals and possibly the easy chemos. I'd like to give immunotherapy more time to develop. However, if you have no more standard of care options that you want to consider, these are all powerful trials.

>Z<

Catalina- Best of luck!!! We have not heard a lot about CD47 for solid tumors, so I am going to go see if there have been any updates about this or any of the other trials using it. As I understand it, you will be getting both anti-CD47 and checkpoint inhibitors (so, a double-dose of immunotherapy)?