On December 5, 2016 Apogenix, a biopharmaceutical company developing next-generation immuno-oncology therapeutics, reported that the final data from the Phase I clinical trial evaluating the safety and efficacy of asunercept (APG101) in lower (low and intermediate) risk patients with MDS were presented in an oral presentation at this year´s ASH (Free ASH Whitepaper) meeting on December 3, 2016 in San Diego, CA, USA (Press release, Apogenix, DEC 5, 2016, View Source [SID1234524575]).

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Asunercept is a fusion protein consisting of the extracellular domain of human CD95-receptor and the Fc domain of a human IgG1 antibody. Asunercept binds to the CD95-ligand on cells as well as to the soluble ligand, thus blocking the interaction between CD95-receptor and its cognate ligand. CD95-receptor is overexpressed on erythroid progenitor cells in the majority of patients with lower-risk MDS. Activation of CD95-receptor blocks erythrocyte production in the bone marrow. Its overexpression is a predictive factor of resistance to erythropoiesis stimulating agents (ESAs). In this Phase I study, all 20 patients enrolled were eligible for inclusion if they suffered from anemia resulting in a high transfusion burden, had hemoglobin levels of less than 10 g/dL, and were refractory to ESAs. Patients received once-weekly asunercept infusions for 12 weeks. Eight of the 20 patients (40%) showed a marked reduction of transfusion frequency for 6 months (end of observation period). Asunercept was generally well tolerated with no reported grade 3 or higher related adverse events. The most common treatment-emergent adverse events included peripheral edema (6 patients), urinary tract infection (4 patients), and oral herpes (3 patients).

"MDS patients display inappropriately increased CD95-receptor mediated signaling in the bone marrow, resulting in ineffective erythropoiesis," Prof W.K. Hofmann, head of the Department of Oncology & Hematology at the University Mannheim Heidelberg and study investigator, explained. "Asunercept inhibits this signaling pathway and promotes early-and late-stage erythroid differentiation, thereby correcting the ineffective erythropoiesis."

"Even though the study was only designed as a safety and pharmacodynamic Phase I trial, the results of short-term asunercept treatment in lower-risk MDS patients are very exciting," Harald Fricke, MD, Chief Medical Officer of Apogenix, said. "There is a substantial unmet medical need for patients who are refractory to treatment with ESAs and we look forward to continuing development of asunercept for this important indication."

Based on the effect of asunercept on early-and late-stage erythroid differentiation and the encouraging clinical activity in these patients, additional clinical Phase II studies are in preparation to test asunercept in lower-risk MDS patients with resistance to ESA treatment.

About Asunercept (APG101)
Apogenix’s lead immuno-oncology candidate asunercept is a fully human fusion protein that consists of the extracellular domain of the CD95-receptor and the Fc domain of an IgG1 antibody. Asunercept is being developed for the treatment of solid tumors and malignant hematological diseases. The World Health Organization (WHO) has recently assigned the international nonproprietary name (INN) "asunercept" for APG101.

On December 5, 2016 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported efficacy and safety findings from a Phase 2 study demonstrating that nearly half (48%) of patients with relapsed/refractory (R/R) marginal zone lymphoma (MZL) had a complete or partial response with single-agent ibrutinib (IMBRUVICA), as assessed by Independent Review Committee (IRC) investigators (Press release, AbbVie, DEC 5, 2016, View Source [SID1234516940]). The median duration of response was not reached.1 These data will be presented today in an oral presentation at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, CA (abstract #1213). IMBRUVICA, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

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MZL is a diverse group of slow-growing non-Hodgkin’s lymphomas arising from white blood cells (lymphocytes) at the edges of lymphoid tissue.2 MZL accounts for approximately 12% of all cases of non-Hodgkin’s lymphoma in adults and the median age at diagnosis is 65 years old.3 There are currently no approved treatments or standards of care specifically indicated for patients with MZL in the United States.

"We are pleased with the 48% response rate seen with ibrutinib in this trial, as the hematology-oncology community has a need for effective new therapies to treat marginal zone lymphoma," said Ariela Noy, M.D., Hematologic Oncologist at Memorial Sloan Kettering Cancer Center in New York and lead investigator of the study.* "In particular, a non-chemotherapy targeted oral option like ibrutinib could represent an important step forward for patients with MZL to keep this incurable type of cancer under control."

In this multicenter, open-label trial, 63 MZL patients (including splenic MZL [SMZL], nodal MZL [NMZL] and extranodal MZL [EMZL] subtypes) received one or more prior therapies including at least one CD20-directed regimen (chemo-immunotherapy or rituximab monotherapy). In the study, 79% of patients experienced some tumor reduction (50 out of 63 patients) and overall response rates (ORR) was 48%, implying that BTK signaling is an important growth and survival factor in MZL. The median time to initial response was 4.5 months.1

Overall, the safety data from this study was consistent with the known safety profile of ibrutinib in B-cell malignancies. The most common adverse events (AEs) included fatigue (44%), diarrhea (43%), anemia (33%), nausea (25%), thrombocytopenia, peripheral edema and arthralgia (24% each), cough (22%), dyspnea and URTI (21% each). Grade 3 or 4 AEs occurred in 63% of patients. The most frequent were anemia (14%), pneumonia (8%) and fatigue (6%). Grade 1 and 2 atrial fibrillation occurred in four (6%) patients.1

"These findings contribute to the growing body of evidence exploring the use of ibrutinib in different types of hematologic cancers, including marginal zone lymphoma and its three sub-types," said Darrin Beaupre, M.D., Ph.D., Head of Early Development and Immunotherapy at Pharmacyclics LLC, an AbbVie company. "Results from this study support the recent submission of a supplemental New Drug Application to include more patients who may benefit from treatment with ibrutinib."

About the Study
The Phase 2 study evaluated the safety and efficacy of ibrutinib in patients with R/R MZL. The primary objective of the trial was ORR as assessed by an IRC. Duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety were secondary objectives.1 Data from this study were submitted to the U.S. Food and Drug Administration (FDA) in September 2016 as part of a supplemental New Drug Application (sNDA) to expand the current indication for IMBRUVICA.

About IMBRUVICA
IMBRUVICA is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.4,5 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.4

IMBRUVICA is approved to treat patients with CLL/SLL including patients with 17p deletion, patients with mantle cell lymphoma who have received at least one prior therapy and patients with Waldenström’s macroglobulinemia. Accelerated approval was granted for the MCL indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.4

IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry with nearly 30 (n=27) company-sponsored trials underway, 14 of which are Phase 3. In addition, there are more than 40 (n=44) investigator-sponsored trials taking place around the world. To date, more than 65,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage – Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA.

The mechanism for the bleeding events is not well understood. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding.

Infections – Fatal and nonfatal infections have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA. Evaluate patients for fever and infections and treat appropriately.

Cytopenias – Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 9%) based on laboratory measurements occurred in patients treated with single agent IMBRUVICA. Monitor complete blood counts monthly.

Atrial Fibrillation – Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines.

Hypertension – Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate.

Second Primary Malignancies – Other malignancies (range, 5% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4% to 13%).

Tumor Lysis Syndrome – Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity – Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

ADVERSE REACTIONS

The most common adverse reactions (?20%) in patients with B-cell malignancies (MCL, CLL/SLL, and WM) were neutropenia** (64%), thrombocytopenia** (63%), diarrhea (43%), anemia** (41%), musculoskeletal pain (30%), rash (29%), nausea (29%), bruising (29%), fatigue (27%), hemorrhage (21%), and pyrexia (21%).

**Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).

The most common Grade 3 or 4 non-hematologic adverse reactions (?5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).

Approximately 6% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse reactions.

Approximately 4%-10% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse reactions. Most frequent adverse reactions leading to discontinuation were pneumonia, hemorrhage, atrial fibrillation, rash and neutropenia (1% each) in CLL patients and subdural hematoma (1.8%) in MCL patients.

DRUG INTERACTIONS

CYP3A Inhibitors – Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose.

CYP3A Inducers – Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment – Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA dose.

Please see Full Prescribing Information: View Source

On December 5, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported data from the positive, pivotal Phase III GALLIUM study that compared Gazyva/Gazyvaro (obinutuzumab) plus chemotherapy followed by Gazyva/Gazyvaro alone head-to-head against MabThera/Rituxan (rituximab) plus chemotherapy followed by MabThera/Rituxan alone for people with previously untreated follicular lymphoma. At a pre-planned interim analysis in May 2016, an independent data monitoring committee determined that the study met its primary endpoint early. The results showed Gazyva/Gazyvaro-based treatment reduced the risk of disease worsening or death (progression-free survival; PFS, as assessed by investigator) by 34 percent compared to MabThera/Rituxan-based treatment (HR=0.66; 95% CI 0.51-0.85, p=0.0012). Median PFS was not yet reached. Adverse events with either Gazyva/Gazyvaro or MabThera/Rituxan were consistent with those seen in previous studies.
"Follicular lymphoma, the most common slow-growing form of non-Hodgkin lymphoma, is an incurable blood cancer characterized by cycles of remission and disease progression, and becomes harder to treat with every relapse," said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. "This study of Gazyva/Gazyvaro-based treatment is the first and only Phase III trial to date to show superior progression-free survival compared to MabThera/Rituxan-based treatment, the current standard of care, in previously untreated follicular lymphoma."
The primary results from the GALLIUM study (Abstract #6) were presented during the Plenary Scientific Session of the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego by Dr. Robert Marcus, King’s College Hospital, London and the National Cancer Research Institute (NCRI), on Sunday, December 4 at 2:00 P.M. PST. Additionally, an analysis of minimal residual disease (MRD) status in the GALLIUM study (Abstract #613) was presented in a separate oral session by Dr. Christiane Pott, University Hospital Schleswig-Holstein, Kiel, Germany, and the German Low Grade Lymphoma Study Group (GLSG) on Monday, December 5 at 7:00 A.M. PST.
GALLIUM is the third positive Phase III study for Gazyva/Gazyvaro, following the CLL11 study in patients with previously untreated chronic lymphocytic leukaemia (CLL) and the GADOLIN study in patients with indolent (slow-growing) non-Hodgkin lymphoma whose disease progressed during or within six months of prior MabThera/Rituxan-based therapy. The results of the GALLIUM study will be submitted to health authorities around the world for approval consideration.
About the GALLIUM study
GALLIUM (NCT01332968) is a global Phase III open-label, multi-centre, randomised two-arm study examining the efficacy and safety of Gazyva/Gazyvaro plus chemotherapy followed by Gazyva/Gazyvaro alone for up to two years, as compared head-to-head against MabThera/Rituxan plus chemotherapy followed by MabThera/Rituxan alone for up to two years. Chemotherapies used were CHOP, CVP or bendamustine and were selected by each participating study site prior to beginning enrolment. GALLIUM included 1401 patients with previously untreated indolent non-Hodgkin lymphoma (iNHL), of which 1202 patients had follicular lymphoma. The primary endpoint of the study was investigator-assessed PFS in patients with follicular lymphoma, with secondary endpoints including PFS assessed by independent review committee (IRC), PFS in the overall study population (iNHL), response rate (overall response, ORR; and complete response, CR), overall survival (OS), and safety. The GALLIUM study is being conducted in cooperation with the GLSG (Germany), the East German Study Group Hematology and Oncology (OSHO; Germany) and the NCRI (United Kingdom).
A summary of the GALLIUM study results presented at ASH (Free ASH Whitepaper) is included below.

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1 Primary endpoint is PFS as assessed by investigator; median follow-up of 34.5 months
2 Measured by computerized tomography (CT) scans
3 MRD-negativity means no cancer can be detected in the blood or bone marrow using a specific highly sensitive test
4 Defined as any AE occurring during or within 24 hours of infusion of Gazyva/Gazyvaro or MabThera/Rituxan and considered drug-related
About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyva/Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system.
Gazyva/Gazyvaro is currently approved in more than 80 countries in combination with chlorambucil, for people with previously untreated chronic lymphocytic leukaemia. The approvals were based on the CLL11 study, showing significant improvements with Gazyva/Gazyvaro plus chlorambucil across multiple clinical endpoints, including PFS, overall response rate (ORR), complete response rate (CR), and minimal residual disease (MRD) when compared head-to-head with MabThera/Rituxan plus chlorambucil.
In February 2016, Gazyva was approved by the US Food and Drug Administration in combination with bendamustine followed by Gazyva alone for people with follicular lymphoma who did not respond to a Rituxan-containing regimen, or whose follicular lymphoma returned after such treatment. In June 2016, Gazyvaro was approved by the European Commission in combination with bendamustine followed by Gazyvaro maintenance in people with follicular lymphoma who did not respond or who progressed during or up to six months after treatment with MabThera or a MabThera-containing regimen. Both approvals were based on the phase III GADOLIN study, showing a significant improvement in progression-free survival with Gazyva/Gazyvaro-based therapy compared to bendamustine alone. Gazyva is marketed as Gazyvaro in the EU and Switzerland.
Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.
About follicular lymphoma
Follicular lymphoma is the most common indolent (slow-growing) form of non-Hodgkin lymphoma (NHL), accounting for about one in five cases of NHL.2 It is considered incurable and relapse is common. It is estimated that more than 75,000 people are diagnosed with follicular lymphoma each year worldwide.3

On December 4, 2016 Nordic Nanovector ASA (OSE: NANO) reported the updated results from its ongoing Lymrit 37-01 Phase 1/2 clinical trial of Betalutin (177Lu-satetraxetan-lilotomab) in subjects with relapsed non-Hodgkin lymphoma (NHL) at the 58th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) meeting (San Diego, CA, USA) (Press release, Nordic Nanovector, DEC 4, 2016, View Source [SID1234516900]).

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The updated data confirm Betalutin’s promising efficacy and favourable safety profile as a single agent in 38 relapsed NHL patients, having failed multiple prior regimens and being eligible for assessments. The results, based on the data cut-off date of 31 October 2016, were presented by the study’s Principal Investigator Dr. Arne Kolstad from the Department of Oncology at the Oslo University Hospital, Radiumhospitalet.

Key conclusions:

• In the 35 patients evaluable for efficacy, the Overall Response Rate (ORR) was 63%, with 29% Complete Responses (CR)

• The 21 evaluable patients in the study who received Betalutin at the dose of 15 MBq/kg with 40 mg/m2 lilotomab pre-dosing had an ORR of 62% and a CR of 38%; of these, the 16 patients enrolled in the Phase 2 expansion of Arm 1, had an ORR of 69% and a CR of 38%

• Durable responses have been observed with a median duration of response of 20.7 months for all patients in Arm 1

• Betalutin is well tolerated, with a predictable and manageable safety profile: most adverse events are haematological in nature, and all have been transient and reversible

• No dose-limiting toxicity (DLT) was reported in Arm 4 (15 MBq/kg Betalutin plus 100 mg/m2 lilotomab pre-dosing) and this regimen demonstrated lower bone marrow toxicity than Arm 1, 2 and 3. Arm 4 is now enrolling patients to evaluate the higher dosing regimen of 20 MBq/kg Betalutin plus 100 mg/m2 lilotomab.

The Lymrit 37-01 study is a Phase 1/2 open label, dose escalation study investigating the optimal lilotomab pre-dosing and Betalutin regimen in patients with relapsed NHL. Data from 38 patients are presented.

Dr. Arne Kolstad, MD commented: "The results we are presenting today are very encouraging and continue to highlight the potential of Betalutin to provide a new treatment option for NHL patients. These patients, particularly those who fail standard CD20-targeted immunotherapy and/or are too frail to receive chemotherapy, are desperately in need of alternative therapies that work through different and complementary mechanisms and are well tolerated. Betalutin is showing exciting promise in an increasing number of NHL patients and we look forward to the results from future studies that will hopefully confirm its attractive profile."

Dr. Lisa Rojkjaer, MD Nordic Nanovector’s Chief Medical Officer, commented: "These new data confirm the promising results for Betalutin, including durable responses in a number of patients, which were presented earlier this year at the AACR (Free AACR Whitepaper) meeting, and continue to demonstrate an encouraging clinical profile as a single agent for treating patients with relapsed NHL. The results also support escalating to a higher dosing regimen in the final stages of this Phase 1/2 study that will allow us to decide an optimal dosing regimen for the pivotal Phase 2 study, PARADIGME, expected in Q1 2017."

The poster (abstract 1780) is available at: View Source

On December 4, 2016 Acetylon Pharmaceuticals, Inc., the leader in the development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes, reported that it will present initial clinical data from a Phase 1a/1b clinical trial evaluating the safety and preliminary anti-tumor activity of the selective HDAC6 inhibitor citarinostat (ACY-241), in combination with pomalidomide (Pom) (Pomalyst, Celgene) and dexamethasone (Dex) for the treatment of relapsed or relapsed-and-refractory multiple myeloma (RRMM) at the 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, California (Press release, Acetylon, DEC 4, 2016, View Source [SID1234516901]).

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"Early results of this study with citarinostat closely parallel recently published positive data for the Phase 2 trial of Acetylon’s first selective HDAC6 inhibitor ricolinostat in combination with Pom and Dex in multiple myeloma, and compare favorably to historical controls. In early follow-up data for Celgene’s MM-003 trial of Pom/Dex versus high dose Dex, there was a 17% overall response rate at 4.2 months. At a 4-month median follow up with citarinostat in combination with the same Pom/Dex regimen, we are seeing an impressive overall response rate of 46% as well as substantial improvement in progression free survival standing at 6.5 versus historical 4 months," said Robert Markelewicz, Senior Medical Director at Acetylon. "While these are still interim data, we are seeing that citarinostat combines favorably with Pom and Dex, and we will continue cohort expansion to explore selected biomarkers and confirm the dose and schedule for a planned pivotal trial."

Citarinostat (ACY-241) is an orally available selective HDAC6 inhibitor that is structurally similar to ricolinostat (ACY-1215), and administered in tablet form. The ACE-MM-200 study is a Phase 1a/1b clinical trial to determine the maximum tolerated dose, safety, and preliminary anti-tumor activity of citarinostat alone and in combination with pomalidomide and dexamethasone in patients with relapsed or relapsed-and-refractory multiple myeloma. Its sequential monotherapy/combination trial design allows patients access to combination therapy based on an established regimen starting in the second cycle of treatment, while establishing the safety, pharmacokinetics, and pharmacodynamics of citarinostat as both a monotherapy and in combination.

Initial results of the study suggest that citarinostat is well tolerated, with no maximum tolerated dose (MTD) observed at doses up to 480 mg once-a-day as a monotherapy and up to 360 mg once-a-day in combination with Pom/Dex. Tolerability in combination is similar to that reported for Pom/Dex alone. In 56 efficacy evaluable patients with a 4-month median follow-up, the confirmed overall response rate (ORR) was 46%, with a clinical benefit rate (CBR) of 59% and disease control rate (DCR) of 91%. The median duration of response (DOR) was 9.2 months and median progression-free survival (PFS) was 6.5 months. Notably, similar response rates were seen across the refractory subsets, including patients who were previously refractory to pomalidomide and daratumumab. A dose of 360 mg once-a-day was selected as the recommended Phase 2 dose for citarinostat based on similarly low incremental toxicity, higher PK/PD exposure, and similar clinical efficacy when compared to the 180 mg dose.

Details of the presentation are as follows:

Date: Sunday, December 4, 2016

Time: 6:00pm – 8:00pm PST

Location: Hall GH (San Diego Convention Center)

Session: 653. Myeloma: Therapy, excluding Transplantation: Poster II

Abstract Number: 3307

Title: Selective HDAC6 Inhibitor ACY-241, an Oral Tablet, Combined with Pomalidomide and Dexamethasone: Safety and Efficacy of Escalation and Expansion Cohorts in Patients with Relapsed or Relapsed-and-Refractory Multiple Myeloma (ACE-MM-200 Study)

About HDAC6 Selective Inhibition

Citarinostat (ACY-241) and ricolinostat (ACY-1215) selectively inhibit the intracellular enzyme HDAC6, leading to an accumulation of excess protein and disrupting critical proliferative signals in malignant cells. Disruption of these molecular processes in cancer cells triggers programmed cell death, called "apoptosis," with little or no effect on normal cells. HDAC6 inhibition also enhances immune responses to cancer cells, both singly and in synergistic combination with immunomodulatory drugs (IMiDs), immune checkpoint inhibitor antibodies, and/or cytotoxic antibodies. Currently available HDAC drugs non-selectively affect the expression of numerous other genes in normal cells as well as cancer cells, which can result in side effects such as gastrointestinal dysfunction, lowered blood platelet levels and risk of hemorrhage, and profound fatigue as well as potential for significant cardiac toxicity. Selective inhibition of HDAC6 is anticipated to reduce or eliminate these often-severe side effects associated with non-selective HDAC inhibition and to enable the development of optimized treatment regimens, including maximally effective combination drug therapies.