ASCO 2015 Multiple Myeloma Update – Poster Presentations: Potential New Myeloma Therapies

A session last Sunday at the 2015 American Society of Clinical Oncology (ASCO) annual meeting featured a number of poster presentations related to multiple myeloma.
During “poster sessions” at conferences such as the ASCO meeting, research results are made available for review by meeting attendees in the form of posters, each of which summarizes the results of a single study. Each poster is typically about two feet high by three or four feet in length, and all posters during a session are displayed throughout a large conference hall.
Most of the myeloma-related posters at the ASCO session last Sunday focused on research related to either currently approved myeloma therapies or potential new myeloma treatments. This ASCO 2015 update from The Beacon will focus on the posters about potential new therapies.
An earlier ASCO 2015 update summarized research about therapies currently approved in the United States for the treatment of multiple myeloma. It also covered research presented during the session that was related to the impact of specific chromosomal abnormalities, such as del(17p) and t(11;14), on the prognosis of myeloma patients (see related Beacon news).
Elotuzumab
One of the posters at last Sunday’s session summarized the results of a Phase 2 trial that compared the efficacy and safety of two treatment regimens: elotuzumab in combination with Velcade (bortezomib) and dexamethasone (Decadron); and Velcade and dexamethasone alone (abstract #8573).
Elotuzumab is being developed by the pharmaceutical companies Bristol-Myers Squibb (NYSE: BMY) and AbbVie (NYSE:ABBV). It belongs to a class of drugs known as monoclonal antibodies. These drugs identify cancer cells through specific proteins on the surface of those cells. Once they have identified the cancer cells, the drugs either signal the immune system to attack the cancer cells, or they attack the cells themselves, or they do both (signal and attack on their own).
Elotuzumab, which is given as an infusion, targets a protein known as SLAM7 (also known as CS1). The protein is commonly found on the surface of myeloma cells.
RELATED LINKS Lists of ASCO 2015 - Oral presentations |
The study presented during the ASCO poster session included 152 myeloma patients with an average age of 64 years who had received between one to three prior lines of therapy. The overall response rate was similar between the two treatment groups (65 percent for elotuzumab, Velcade, and dexamethasone, versus 63 percent for Velcade and dexamethasone alone). Median progression-free survival was longer, however, for patients receiving elotuzumab, Velcade, and dexamethasone (9.7 months), compared to patient receiving Velcade and dexamethasone alone (6.9 months).
The researchers also observed a trend for longer overall survival for patients receiving the elotuzumab combination. The one-year median overall survival rate was 85 percent for patients receiving elotuzumab, Velcade, and dexamethasone versus 74 percent for patients receiving Velcade and dexamethasone alone.
The most common side effects observed in the patients who received the three-drug regimen included infections (65 percent), diarrhea (43 percent), constipation (39 percent), and cough (39 percent). Infusion reactions, which may occur with elotuzumab, occurred in 7 percent of patients and were all mild in nature.
Evofosfamide (TH-302)
Initial results from a Phase 1 study of evofosfamide (TH-302) and dexamethasone with or without Velcade in heavily pretreated myeloma patients were also presented during the poster session (abstract #8579; poster [PDF] courtesy of Dr. Jacob Laubach). TH-302 is being developed by Threshold Pharmaceuticals (NASDAQ: THLD) and the German pharmaceutical company Merck KGaA for the treatment of several different types of cancer. It is an infused drug that is activated under low oxygen level conditions, which are common in solid cancer tumors and in the bone marrow of people with blood cancers.
The TH-302 study in myeloma thus far has recruited 25 patients. Of those patients, 18 have received TH-302, Velcade, and dexamethasone and have been evaluated for response. These patients had received a median of eight prior therapies. One of the 18 patients (6 percent) achieved a complete response and two (11 percent) achieved a partial response; all of these three patients received the higher of the two tested dose levels. In addition, one patient (6 percent) achieved a minor response and two patients (11 percent) achieved stable disease. The most common side effects of the treatment included low platelet counts (72 percent, anemia (56 percent), and nausea (44 percent).
MOR202
Another poster summarized the results of a Phase 1/2b trial of MOR202 in relapsed and refractory multiple myeloma patients (abstract #8574; poster [PDF] courtesy of Dr. Marc Raab). MOR202, which is an infused drug being developed by the Germany pharmaceutical company MorphoSys, is a monoclonal antibody that targets the CD38 protein commonly found on myeloma cells. CD38 is the same protein targeted by daratumumab and SAR650984, two other monoclonal antibodies also under investigation as potential myeloma therapies.
At the time the data for the MOR202 poster were analyzed, results were available for 42 patients, who were treated with single-agent MOR202 at several different doses. These patients had age of 70 and had received a median of four prior therapies, including at least one immunomodulatory agent, such as Revlimid or thalidomide, and one proteasome inhibitor, such as Velcade.
Thus far, one of the 42 patients has responded to treatment with single-agent MOR202, achieving a very good partial response. The most common side effects have included anemia (33 percent), fatigue (33 percent), nausea (26 percent), low lymphocyte count (19 percent), and low white blood cell counts (19 percent).
Venetoclax (ABT-199)
Two posters about venetoclax (ABT-199) as a potential myeloma therapy were presented during the ASCO session. Venetoclax is an orally administered drug that targets Bcl-2 and Bcl-2-related proteins, which regulate cell death. It is being developed by the U.S. pharmaceutical company AbbVie in collaboration with the Swiss pharmaceutical company Roche. Venetoclax has shown good activity in preclinical studies, particularly in myeloma cells with the chromosomal abnormality t(11;14).
The first venetoclax poster summarized the interim results from a Phase 1 trial of the drug as monotherapy in relapsed and refractory multiple myeloma (abstract #8576; poster [PDF] courtesy of Dr. Shaji Kumar). So far the trial has recruited 29 patients with a median age of 66 years who had received a median of six prior therapies. Almost half of the patients (41 percent) had t(11;14)-positive myeloma cells; 18 percent of these patients responded with a complete response. Best response among patients without t(11;14) was stable disease. The most common side effects included diarrhea (41 percent), nausea (41 percent), fatigue (24 percent), and vomiting (24 percent).
The second poster reported findings from a Phase 1b trial of venetoclax in combination with Velcade and dexamethasone in relapsed and refractory myeloma (abstract #8580; poster [PDF] courtesy of Dr. Cyrille Touzeau). So far, 38 patients with a median age of 65 years who received a median of five prior therapies have been enrolled in the trial. Overall 47 percent of patients achieved a partial response or better with the venetoclax combination. These responses, however, were only observed in patients who were not resistant (refractory) to Velcade, or had never been treated with Velcade. The best response observed in patients who were resistant to Velcade was a minor response. The most common side effects included constipation (37 percent), diarrhea (32 percent), low platelet counts (29 percent), and peripheral neuropathy (26 percent).
CUDC-907
Another poster during the ASCO session presented results of a Phase 1 trial of CUDC-907 in patients with relapsed or refractory multiple myeloma or lymphoma (abstract #8537; poster [PDF] courtesy of Dr. Jesus Berdeja). CUDC-907, which is being developed by the pharmaceutical company Curis (NASDAQ:CRIS), is an orally administered drug that inhibits both PI3K and histone deacetylase (HDAC) enzymes.
Farydak (panobinostat) was the first HDAC inhibitor approved to treat multiple myeloma. Other HDAC inhibitors that have been – or currently are being – investigated as potential myeloma therapies include Zolinza (vorinostat), and ricolinostat (ACY-1215).
Perifosine, a combined Akt and PI3k inhibitor, was once in clinical trials as a potential myeloma therapy, but its development has been halted. Zydelig (idelalisib), the first PI3K inhibitors approved as a cancer therapy, is used in the treatment of certain types of leukemia and lymphoma. It also was tested as a treatment for multiple myeloma in an early stage clinical trial, but results of that study were never published. Other PI3k inhibitors are currently being investigated as potential blood cancer therapies, primarily leukemia and lymphoma.
The CUDC-907 study presented at ASCO included 57 patients who had received a median of five prior treatment regimens. Patients in the trial received single-agent CUDC-907. Several different doses of the drug were tested, as were several different dosing frequencies.
Nine patients in the study had multiple myeloma. Among these nine patients, one responded, achieving a minor response; three patients achieved stable disease for at least a short period of time; and three patients have results that are not yet evaluable. One of the three patients who achieved stable disease is still stable two years after starting treatment with CUDC-907.
Across all patients in the study, the most common side effects included diarrhea, fatigue, nausea, and low platelet counts.
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For all Beacon articles related to this year’s ASCO meeting, see The Beacon’s full ASCO 2015 coverage. In addition, The Beacon has complete lists of all ASCO 2015 myeloma-related oral presentations, poster presentations, education session presentations, and e-abstracts.
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