This article is the second in The Beacon’s ‘preview’ series about mye­lo­ma re­search that will be pre­sented at the American Society of Hema­tol­o­gy (ASH) meet­ing in early December.

Abstracts for the ASH presentations are now available; these abstracts contain pre­lim­i­nary data, and updated data will be presented at the meet­ing.

The Beacon's ASH preview articles, which will be published over the next couple of weeks, will highlight the most interesting myeloma-related studies that will be presented at the meeting.

The first preview, which was published last Friday, provides an overview of ASH abstracts about the newest potential myeloma therapies just starting out in clinical trials.

Today's preview continues with the "new treatments" theme, but turns its attention to therapies that are bit further along in development.   Clinical trial results for the therapies covered below have been discussed at some major medical conferences in the past -- but not many of them.

In particular, this article discusses abstracts for indatuximab ravtansine (BT062), oprozomib, ricolinostat (ACY-1215), TH-302, and veliparib.

Clinical results for another drug, quisinostat, also will be presented at ASH.  However, all results in the quisinostat abstract were presented earlier this year at the American Society of Clinical Oncology (ASCO) annual meeting (see related Beacon news), so they are not discussed any further in this article.

Many of the results summarized below are promising.

The combination of indatuximab ravtansine (BT062), Revlimid (lenalidomide), and dexamethasone (Deca­dron), for example, yielded an overall response rate of 78 percent in heavily pretreated myeloma patients.  In addition, patients who did not respond to the three-drug combination nevertheless were able to achieve stable disease.

Ricolinostat and TH-302 also appear to be active when combined with Revlimid and dexamethasone, and the overall response rate in the trial of oprozomib as a single agent appears to be comparable to what was seen with Kyprolis (carfilzomib) in its initial clinical trials as a single agent.

Indatuximab Ravtansine

At ASH, results will be presented from a Phase 1/2a study of indatuximab ravtansine (BT062) in combination with Revlimid and dexamethasone in relapsed and refractory myeloma patients (abstract).

Indatuximab ravtansine is being developed by the German pharmaceutical company Biotest.  It is a com­pound that combines a chemotherapeutic drug (ravtansine) with an antibody (indatuximab) that helps deliver the drug to myeloma and other cancer cells. When the compound enters a cancer cell, it releases the che­mo­ther­a­py drug that ultimately kills the cell.

The study includes 15 patients who had received a median of four prior lines of therapy; half were resistant to prior Revlimid-dexamethasone therapy.  Among the 9 patients currently available for response, the overall response rate was 78 percent, with 11 percent achieving a complete response, 11 percent a very good partial response, and 55 percent a partial response.  The remaining 22 percent achieved stable disease.

Oprozomib

Interim results of an ongoing Phase 1b/2 clinical trial of oprozomib in patients with multiple myeloma and Waldenström's macro­glob­uli­nemia will also be presented at the meeting (abstract).

Oprozomib is being developed by Onyx Pharmaceuticals (NASDAQ: ONXX), the company that markets Kyprolis.  Oprozomib is a proteasome inhibitor like Velcade (bortezomib) and Kyprolis.  These drugs work by preventing the breakdown of protein in cancer cells, triggering their death.  Oprozomib, unlike Kyprolis and Velcade, can be taken orally. First clinical results about oprozomib were presented at last year’s ASH annual meeting (see related Beacon news).

The study includes 42 relapsed patients (30 with multiple myeloma and 12 with Waldenström's macro­glob­ulinemia) who were treated with oprozomib, using one of two different dosing schedules.  About one quarter (23 percent) of the myeloma patients in the one dosing group responded to treatment, with 8 percent achieving a very good partial response and 15 percent achieving a partial response, while none of the myeloma patients in the second dosing group responded to treatment.

Ricolinostat

Several studies of ricolinostat (ACY-1215) will be presented at this year’s ASH meeting.

Ricolinostat is being developed by Acetylon Pharmaceuticals.  It belongs to a class of drugs known as oral histone deacetylase (HDAC) inhibitors. Several HDAC inhibitors are being investigated for the treatment of multiple myeloma, including Zolinza (vorinostat), panobinostat, and quisinostat.  The drugs in this class work by interrupting cell division and causing cell death. However, ricolinostat is believed to be more se­lec­tive than other HDAC inhibitors, which means that it could be more effective and have fewer side effects.

The first study is a Phase 1 trial of ricolinostat plus Velcade (abstract).  The most recent results of the trial were presented as a poster at the European Hematology Association (EHA) annual meeting this summer (see related Beacon news).

The study includes 16 relapsed and refractory myeloma patients who had received up to 11 prior lines of therapy.  Overall, 19 percent of patients responded to therapy, with 6 percent achieving a very good partial response and 13 percent a partial response.  None of the patients who were resistant to previous Velcade therapy, however, responded to the ricolinostat combination therapy.

Another ricolinostat study, a Phase 1b study in which the drug is given in combination with Revlimid and dexamethasone, will be presented at the meeting (abstract).  The results of this study are also an update to those presented in this summer's EHA poster.

The ricolinostat-Revlimid-dexamethasone study included 15 relapsed and refractory myeloma patients who had received one to three prior lines of therapy.  Among the 13 patients evaluable for response, 69 percent responded, with 8 percent achieving a complete response, 31 percent a very good partial response, 23 percent a partial response, and 8 percent an unconfirmed partial response.  Among the patients who were resistant to previous Revlimid therapy, 33 percent responded to the ricolinostat com­bi­na­tion therapy.

TH-302

At the ASH meeting, updated results from a Phase 1 study of TH-302 plus dexa­metha­sone in heavily pre­treated myeloma patients will be presented (abstract). Initial results of the study were presented earlier this year at the ASCO annual meeting (see related Beacon news).

TH-302 is being developed by Threshold Pharmaceuticals (NASDAQ: THLD) and the German pharma­ceut­i­cal company Merck KGaA. TH-302 is a drug that is activated under low oxygen level conditions, which are common in tumors and the bone marrow of people with blood cancers. It is currently also being investigated in a range of solid tumors.

The study includes 13 patients who had received a median of six prior lines of therapy. Of the 12 patients evaluated for response, 17 percent achieved a partial response.  In addition, 17 percent reached a minimal response, and 67 percent had stable disease.

Veliparib 

Updated results of an ongoing Phase 1 study of veliparib in combination with Velcade and dexamethasone in relapsed / refractory myeloma patients will be presented at the ASH meeting (abstract). Initial results of this trial were presented at last year’s ASH annual meeting (see related Beacon news).

Veliparib, which is being developed by AbbVie (formerly Abbott Laboratories), inhibits the activity of the en­zymes PARP1 and PARP2.  This, in turn, inhibits DNA repair and thus makes cancer cells more sus­cep­ti­ble to other chemotherapies. Veliparib is being studied as a treatment for a variety of different cancers.

The study includes 19 patients who had received a median of three prior lines of therapy. Of the 18 patients evaluable for response, 39 percent of patients responded, with 22 percent achieving a complete response and 17 percent a very good partial response or a partial response. An additional 50 percent achieved a min­i­mal response or stable disease.  The median progression-free survival was 5 months, and 71 percent were alive at 18 months.

For information about additional studies that will be presented at ASH, see a list of all myeloma-related ASH abstracts, all abstracts about new treatments under development for myeloma, clinical trial results for new treatments, and preclinical research about new treatments.