The California Institute for Regenerative Medicine (CIRM) has funded a study by a company called Forty Seven, Inc. The clinical trial is investigating the benefits of a drug therapy for two cancers with high mortality. The treatment involves the newly developed antibody 5F9 in combination with the chemotherapy drug azacitidine.
The encouraging results of the trial, an objective response rate after four months of 100 percent, were recently announced in an article by the Globe Newswire.
About MDS and AML
MDS, or myelodysplastic syndromes, are a diverse group of disorders caused by bone marrow failure. The bone marrow does not produce a sufficient number of healthy blood cells.
AML or acute myeloid leukemia is also a cancer of the myeloid blood cells. These cells in AML patients does not mature properly. It can quickly become life-threatening.
About The Phase 1b Study
The study was divided into two groups. One arm received 5F9 alone while the second arm received a combination of 5F9 and the drug azacitidine (brand name Vidaza). Azacitidine is one of the new class of drugs called DNA demethylating agents.
DNA methylation involves genes used in the production of chemical compounds within the cells. The tumor suppressor genes make a protein that can control cell growth.
An increase in DNA methylation may result in blocking the suppressor genes that control the division and growth of a cell.
About CD47
Cancer cells send out CD47, which is a signal to macrophages not to destroy the cancer cells. Macrophages are an antigen that engulfs and destroys cancer cells and other proteins not associated with healthy cells. This function, however, is interrupted by the proliferation of CD47.
In response to the invasion of CD47, the body produces antibodies that block the CD47 signal and allow the body’s immune system to find and demolish cancer cells.
5F9 is a monoclonal (binds to one substance) antibody that targets CD47. It binds onto the tumor cells thus blocking its signals.
A total of thirty-five patients were selected for the trial. Ten patients had either MDS or AML and were treated with 5F9 as a single agent antibody.
Eleven patients had MDS and were considered higher risk. These patients were treated with 5F9 in combination with azacitidine.
Fourteen patients who had been diagnosed with AML had received no prior treatment. These patients were treated with 5F9 in combination with azacitidine.
Initial Results of the Study
Upon examination of the eleven higher-risk MDS patients who received the antibody combination, it was discovered that all eleven patients had shown ORR (objective response rate). ORR for this trial meant tumor reduction.
Six of the eleven patients achieved CR (complete response). In most cases, as with this specific trial, CR indicates the disappearance of any sign of cancer as a result of the treatment.
Results obtained upon examination of the fourteen previously untreated AML patients are as follows:
- Median response time was 1.9 months
- ORR was achieved by nine patients
- CR was achieved by five of the nine patients
- MLFS (morphologic leukemia-free state) was achieved by two of the nine patients. MLFS indicates that all cells with the characteristics of leukemia have disappeared. In addition, it indicates the recovery of bone marrow.
- The last five patients had stable disease. The tumors had neither grown nor shrunk.
Toxicity in all instances was not increased when the antibody was combined with the chemotherapy drugs. This provides evidence of tolerance and safety of the therapy.
A follow-up of all patients who participated in the trial after approximately four months found that no patient had relapsed or had disease progression. Several patients even exhibited a deeper response and complete remission.
Moving Forward
The study has been expanded due to favorable results. Additional MDS and AML patients will be added and treated with the 5F9 antibody together with chemotherapy.
One of the investigators in the trial, David Sallman M.D., commented that the goal of physicians is to continue to look for new therapies that will achieve the most durable responses in AML and MDS.
Dr. Sallman expressed his enthusiasm that the majority of those treated with 5F9 and azacitidine exhibited a response time of less than two months without progression of the disease or relapses.