On June 12, 2016 Pfizer Inc. today reported the publication of findings from the Phase 3 INO-VATE ALL study in the online issue of The New England Journal of Medicine (Press release, Pfizer, JUN 12, 2016, View Source [SID:1234513240]). The study, also known as Study 1022, is an open-label, randomized, Phase 3 study evaluating the safety and efficacy of inotuzumab ozogamicin as compared with investigator-choice chemotherapy in 326 adult patients with relapsed or refractory CD22-positive acute lymphoblastic leukemia (ALL). Results showed improvement over chemotherapy on a number of measures including complete hematologic remission and progression-free survival (PFS). Updated results and newly available overall survival (OS) data were also presented as a late-breaking oral presentation (#LB2233) today at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) 2016 Annual Meeting in Copenhagen, Denmark.

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"Relapsed or refractory ALL is an aggressive leukemia in urgent need of new treatment options as about half of adult patients will not respond to chemotherapy or will see their disease return," said Hagop M. Kantarjian, M. D., lead study investigator and professor, The University of Texas MD Anderson Cancer Center. "The efficacy results seen in patients treated with inotuzumab ozogamicin in this study are impressive, particularly median progression-free survival, high rates of hematological remission and absence of minimal residual disease. These results suggest inotuzumab ozogamicin, if approved, could be a valuable new addition to currently available treatment options for ALL patients, including as a bridge to stem cell transplantation, which is the best chance for a cure at this stage of the disease."

The INO-VATE ALL study had two independent primary endpoints, complete response with or without hematologic remission and OS. INO-VATE ALL met its first primary endpoint of complete response, which was significantly better with inotuzumab ozogamicin compared to chemotherapy (80.7% [95% CI, 72%-88%] vs. 29.4% [95% CI, 21%-39%], P<0.001). Inotuzumab ozogamicin also significantly extended PFS compared to chemotherapy (HR: 0.45 [97.5% CI, 0.34-0.61], P<0.001; median PFS, 5.0 vs. 1.8 months, in their respective arms). The second primary endpoint of OS showed a strong trend toward longer OS for patients treated with inotuzumab ozogamicin compared to chemotherapy, but did not reach the level of statistical significance (p < 0.0104) for the trial (HR: 0.77 [97.5% CI, 0.58-1.03], one-sided P=0.0203; median OS, 7.7 months [95% CI, 6.0-9.2] vs. 6.7 months [95% CI, 4.9-8.3]). The two-year OS rate for inotuzumab ozogamicin was 23 percent (95% CI, 16%‒30%) compared to chemotherapy at 10 percent (95% CI, 5%‒16%).

"Adult patients with relapsed or refractory ALL have a five-year survival rate of less than 10 percent, making these patients particularly difficult to treat. To see remission rates and two-year survival rates that are more than doubled compared to standard of care chemotherapy is very gratifying. We believe these data add to the growing body of evidence that supports inotuzumab ozogamicin as an important potential treatment option in adults with relapsed or refractory ALL," said Mace Rothenberg, MD, Chief Development Officer, Oncology, Pfizer Global Product Development.

Results from INO-VATE ALL also showed patients treated with inotuzumab ozogamicin achieved high rates of minimal residual disease (MRD) negativity (78.4% [95% CI, 68%-87%; P<0.001]), and experienced a duration of response (DOR) of 4.6 months (95% CI, 3.9-5.4; HR: 0.55; P<0.034). In comparison, 28.1 percent (95% CI, 14%-47%; P<0.001) of patients treated with chemotherapy achieved MRD negativity and median DOR was 3.1 months (95% CI, 1.4-4.9; HR: 0.55; P<0.034). More patients also proceeded to stem-cell transplant with inotuzumab ozogamicin compared to standard chemotherapy (41% vs. 11%, P<0.001).

The most common adverse events (AEs) observed for both inotuzumab ozogamicin and chemotherapy were cytopenias, including febrile neutropenia (16% vs. 22%). Common nonhematologic treatment-emergent AEs with inotuzumab ozogamicin included nausea (32%), headache (28%) and pyrexia (27%). Patients in the chemotherapy arm experienced nausea (47%), pyrexia (43%) and diarrhea (40%).

Additionally, any-grade veno-occlusive liver disease (VOD) occurred more frequently in patients treated with inotuzumab ozogamicin compared to chemotherapy (11% vs. 1%). Five patients taking inotuzumab ozogamicin developed VOD during treatment and 10 patients developed VOD after subsequent stem cell transplant. Among those taking chemotherapy, one patient developed VOD after transplant; no cases of VOD occurred during treatment with chemotherapy.

Inotuzumab ozogamicin received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for ALL in October 2015. Pfizer is working closely with the FDA and other regulatory authorities with the aim of making inotuzumab ozogamicin available for adult patients with relapsed or refractory CD22-positive ALL.

About Acute Lymphoblastic Leukemia (ALL)

Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia with a poor prognosis in adults.1 The current foundational treatment is intensive, long-term chemotherapy.2 In 2016, it is estimated that 6,590 cases of ALL will be diagnosed in the United States, with about 2 in 5 cases in adults.3 Approximately 20 to 40 percent of newly diagnosed adults with ALL are cured with current treatment regimens.4 For patients with relapsed or refractory adult ALL, the five-year overall survival rate is less than 10 percent.5

About Inotuzumab Ozogamicin

Inotuzumab ozogamicin is an investigational antibody-drug conjugate (ADC) comprised of a monoclonal antibody (mAb) targeting CD22, a cell surface antigen found on cancer cells in almost all B-ALL patients, linked to a cytotoxic agent. 1,6 When inotuzumab ozogamicin binds to the CD22 antigen on malignant B-cells, it is thought to be internalized into the cell, where the cytotoxic agent calicheamicin is released to destroy the cell.7

Inotuzumab ozogamicin originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing and clinical development activities for this molecule.

On June 11, 2016, Boehringer Ingelheim reported the results of the Phase III POLO-AML-2 trial (NCT01721876) investigating volasertib plus chemotherapy (low dose cytarabine LDAC), in the treatment of elderly acute myeloid leukaemia (AML) patients, did not meet the primary endpoint of objective response (Press release, Boehringer Ingelheim, JUN 11, 2016, View Source [SID1234535646]).1 Boehringer Ingelheim is committed to further investigating volasertib with a revised research strategy based on the learnings of the trial, which demonstrated the compound’s anti-leukaemic activity and an increased response rate.
The results presented at the 21st Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) 2016 showed the percentage of patients with an objective response was higher with volasertib plus LDAC, compared to placebo plus LDAC but the difference was statistically not significant.1 The data showed an unfavourable overall survival trend for the experimental treatment arm, with the safety profile of the volasertib plus LDAC dosing regimen considered as the main reason for the trend.1

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Martin Stefanic, Medical Head, Early Clinical Development, Boehringer Ingelheim commented: "We are disappointed with the findings of the POLO-AML-2 trial after the encouraging results we observed in the Phase II trial. However, we believe in the potential of volasertib and new clinical studies have been initiated for AML patients, in addition to other areas of high unmet need such as higher risk myelodysplastic syndromes (MDS). The goal of these studies is to improve tolerability with modified dosing and scheduling of volasertib, while not compromising on efficacy, in order to achieve the best outcome for patients."

POLO-AML-2 (NCT01721876) is a randomised, double-blind, multi-centre, controlled Phase III clinical trial of volasertib in combination with LDAC in 666 patients aged 65 years and older with newly diagnosed AML, not suitable for intensive induction therapy.1 The primary analysis showed a higher number of patients responded to volasertib plus LDAC (25.2%) than placebo plus LDAC (16.8%) but the overall result was not statistically significant.1

There was a higher incidence of severe adverse events with volasertib plus LDAC, with a fatal infection frequency of 16.6% (volasertib plus LDAC) vs 5.1% (placebo plus LDAC) which was considered the main reason for a negative overall survival trend in the volasertib plus LDAC treatment arm compared to placebo plus LDAC (primary OS analysis: HR 1.26 [95% CI 0.95–1.67; p=0.113]; updated OS analysis (Nov 2015): HR 1.06 (95% CI 0.88–1.28; p=0.552).1 The unblinded trial is still ongoing and updated results will be presented at a future scientific meeting when they are available.
Boehringer Ingelheim has a substantial programme in haematological cancers with five investigational compounds in early clinical development.

References
1 Döhner H et al. Phase III randomized tial of volasertib plus low–dose cytarabine (LDAC) versus placebo plus LDAC in patients aged ≥65 years with previously untreated AML, ineligible for intensive therapy. Abstract # S501 presented at the 2016 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting, Copenhagen, Denmark, 9-12 June 2016

On June 11, 2016 Janssen-Cilag International NV reported results from the international Phase 3, randomised, double-blind, placebo-controlled, multicentre study, EPOANE 3021 (Press release, Janssen-Cilag International, JUN 11, 2016, View Source [SID:1234513282]).The study demonstrated the efficacy and safety of EPREX (epoetin alfa) as a treatment for anaemia, in adult patients with low or intermediate-1 risk myelodysplastic syndromes (MDS), as classified by an International Prognostic Scoring System (IPSS).1 EPOANE 3021 data were presented at the 21st Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) (Abstract P248).

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These data, along with three registry studies from across Europe, have been submitted to the French health authority Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM), as the reference health authority for EPREX (epoetin alfa) within the mutual recognition procedure, to extend the existing marketing authorisation in Europe. A decision is expected in the coming months.

EPOANE 3021 was designed to evaluate whether epoetin alfa improves anaemia in patients with MDS, versus placebo over 24-weeks of treatment. It consisted of 130 randomised patients, with 85 patients receiving epoetin alfa. Results showed that compared to placebo, patients in the epoetin alfa arm demonstrated a statistically significantly higher erythroid response rate (according to IWG2006 criteria) in the first 24 weeks, the primary endpoint of the study (31.8 percent vs. 4.4 percent, p<0.001). Significantly fewer patients required transfusion on epoetin alfa (24.7 percent vs. 54.1 percent).1 Additional analysis, accounting for dose adjustments within the protocol, also confirmed a statistically significant erythroid response for epoetin alfa (45.9 percent) compared to placebo (4.4 percent) (p<0.001).1 Quality of life for responding patients in the epoetin alfa arm improved significantly compared to non-responders (FACT-An p=0.025, EQ-5D index score p=0.007, EQ-5D VAS p=0.037). There were no new safety signals for epoetin alfa from the study and safety findings were consistent with the known safety profile of epoetin alfa.1

"Anaemia affects the vast majority of patients with MDS and contributes substantially to their symptoms. However, there are currently no approved erythropoiesis stimulating agents approved for treating anaemia in lower-risk MDS patients," said Pierre Fenaux, M.D., PhD., principal investigator of EPOANE 3021, and Professor of Hematology, Hôpital St Louis/Université, Paris, France. "These data provide important evidence that epoetin alfa can effectively manage lower risk MDS-related anaemia, beyond transfusion, and without any impact on progression to acute myeloid leukaemia (AML)."

"EPREX (epoetin alfa) has shown great potential across a range of indications throughout its clinical development programme. We are excited to be building on this evidence base once again, with the findings of this new study demonstrating the meaningful difference this medicine can make to patients with MDS-related anaemia. We’re also extremely pleased to see the improvements in quality of life offered by EPREX, where alternative treatment options have so far been limited," said Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East and Africa.

For more information on the EPOANE 3021 data presented at EHA (Free EHA Whitepaper) 2016, please view the abstract online.

About the EPOANE 3021 Study1

EPOANE 3021 was a randomised, double-blind, placebo-controlled, multicentre clinical trial investigating the efficacy and safety of EPREX (epoetin alfa) as a treatment for anaemia, in adult patients with low or Intermediate-1 risk myelodysplastic syndromes (MDS), as classified by an International Prognostic Scoring System (IPSS). Results demonstrated that 31.8 percent of patients treated with epoetin alfa achieved the primary endpoint of erythroid response versus 4.4 percent of placebo patients (p<0.001). An ad hoc analysis, accounting for the dose adjustments as per the protocol, confirmed a statistically significant erythroid response for epoetin alfa, with 45.9 percent of epoetin alfa patients, versus 4.4 percent of placebo patients achieving an erythroid response (p<0.001). Median erythroid response duration for epoetin alfa patients was 197 days. The number of patients needing transfusion in the epoetin alfa arm steadily decreased from 51.8 percent in the 8 weeks prior to baseline, to 24.7 percent by week-24. Transfusion need remained unchanged in the placebo patients (48.9 percent – 54.1 percent) over the same interval. Time to first transfusion was longer in the epoetin alfa group (p=0.046). Epoetin alfa demonstrated a statistically significant improvement of quality of life in responding patients.

There were no new safety signals for epoetin alfa from the study and safety findings are consistent with the known safety profile of epoetin alfa. The proportion of patients with at least one treatment emergent adverse event (TEAE) was numerically higher in the placebo group compared with the epoetin alfa group (88.9 percent vs. 77.6 percent). Drug discontinuation due to adverse events was 10.6 percent in the epoetin alfa group versus 13.3 percent in placebo. Four patients in the epoetin alfa arm (4.7 percent) and none in placebo reported a thrombovascular event (TVE). There were four fatal outcomes in the epoetin alfa arm versus one in the placebo arm; none were reported to be related to the study drug. During the study, progression to acute myeloid leukaemia (AML) was similar between groups (3.5 percent in epoetin alfa; 4.4 percent in placebo).

About Myelodysplastic Syndromes (MDS)

Myelodysplastic syndromes (MDS) are a group of diverse bone marrow disorders in which the bone marrow does not produce enough healthy blood cells.2 The low numbers of normal blood cells (cytopenias) eventually cause symptoms, including infection, anaemia, spontaneous bleeding, or easy bruising.2,3 The natural course of MDS is highly variable, with overall survival ranging from a few weeks to several years.4 MDS is primarily a disease of the elderly with a median age at diagnosis of 70 years, but it can affect younger patients as well.4 The incidence in Europe is about four cases per 100,000 per year, reaching 40-50 per 100,000 in patients aged 70 years and over.4

Approximately 60-80 percent of patients with MDS experience symptomatic anaemia,5 which can significantly reduce quality of life and often requires repeated blood transfusions.2 Controlling anaemia and improving quality of life are the principal aims of treatment in lower risk MDS patients.4 At present, blood transfusions are currently the only approved treatment option; however these lead to iron overload, which is associated with significant morbidity and mortality.4,5

About EPREX (epoetin alfa)

EPREX (epoetin alfa) is an erythreopoiesis-stimulating agent (ESA) that works by stimulating the production of red blood cells (RBCs).6 ESAs are an important treatment option for patients with certain types of anaemia, including chemotherapy-induced anaemia and anaemia due to chronic kidney disease. Without ESAs, patients with certain types of anaemia may require regular blood transfusions to maintain RBCs at concentrations necessary to sustain normal oxygen levels throughout the body.4

EPREX is currently indicated for the treatment of:6

Symptomatic anaemia associated with chronic renal failure (CRF):
In adult and paediatric patients aged 1 to 18 years on haemodialysis and adult patients on peritoneal dialysis.
In adults with renal insufficiency not yet undergoing dialysis for the treatment of severe anaemia of renal origin accompanied by clinical symptoms in patients.
Adults receiving chemotherapy for solid tumours, malignant lymphoma or multiple myeloma, and at risk of transfusion as assessed by the patient’s general status (e.g. cardiovascular status, pre-existing anaemia at the start of chemotherapy) for the treatment of anaemia and reduction of transfusion requirements.
Adults in a predonation programme to increase the yield of autologous blood. Treatment should only be given to patients with moderate anaemia (haemoglobin concentration range between 10 to 13 g/dl [6.2 to 8.1 mmol/l], no iron deficiency) if blood saving procedures are not available or insufficient when the scheduled major elective surgery requires a large volume of blood (4 or more units of blood for females or 5 or more units for males).
Non-iron deficient adults prior to major elective orthopaedic surgery having a high perceived risk for transfusion complications to reduce exposure to allogeneic blood transfusions. Use should be restricted to patients with moderate anaemia (e.g. haemoglobin concentration range between 10 to 13 g/dl) who do not have an autologous predonation programme available and with expected moderate blood loss (900 to 1,800 ml).
About the Janssen Pharmaceutical Companies

On June 11, 2016 Seattle Genetics, Inc. (NASDAQ: SGEN) reported data at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) taking place in Copenhagen, Denmark, June 9-12, 2016, evaluating vadastuximab talirine (SGN-CD33A; 33A) in combination with hypomethylating agents (HMAs; azacitidine, decitabine) in frontline patients with acute myeloid leukemia (AML) who had declined intensive therapy (Press release, Seattle Genetics, JUN 11, 2016, View Source;p=RssLanding&cat=news&id=2176948 [SID:1234513211]). 33A is an investigational antibody-drug conjugate (ADC) targeted to CD33 utilizing Seattle Genetics’ newest technology, comprising an engineered cysteine antibody (EC-mAb) stably linked to a highly potent DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer. CD33 is expressed on leukemic blasts in nearly all AML patients with expression generally consistent regardless of age, cytogenetic abnormalities or underlying mutations.

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Based on data from the ongoing phase 1 clinical trial, a phase 3 clinical trial, called CASCADE, was recently initiated evaluating 33A in combination with HMAs in previously untreated AML patients not candidates for intensive induction chemotherapy. Seattle Genetics is also evaluating 33A broadly across multiple lines of therapy in patients with myeloid malignancies, including ongoing and planned phase 1 and 2 clinical trials for newly diagnosed or relapsed AML and for previously untreated myelodysplastic syndrome (MDS). More information about 33A and ongoing clinical trials can be found at www.ADC-CD33.com.

"Hypomethylating agents, or HMAs, are the current standard of care for AML patients who are not able to tolerate intensive therapy. HMAs have limited benefit, with low response rates and median overall survival of 10 months or less," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "We believe that adding 33A to HMAs may improve efficacy and has the potential to redefine the treatment of AML. The clinical data at ASH (Free ASH Whitepaper) showing high response rate, manageable tolerability profile and low early mortality reported have been maintained in this larger data set, and support our recently initiated phase 3 CASCADE clinical trial, which is now enrolling patients."

"There is a dire need to improve outcomes for patients with AML," said Amir Fathi, M.D., investigator of the phase 1 trial who will present the data at EHA (Free EHA Whitepaper). "The anti-leukemic activity we have observed in the phase 1 clinical trial evaluating 33A combination therapy in AML patients continues to be encouraging. This is an incredibly difficult disease to treat and the results to-date continue to show a balance of activity and tolerability together with low early mortality rates. The data presented suggest that the addition of 33A improves the rates of response and durable remissions in comparison to that seen historically from using the current standard of care alone."

SGN-CD33A in Combination with Hypomethylating Agents: A Novel, Well-Tolerated Regimen with High Remission Rate in Older Patients with AML (Abstract #S503, oral presentation on Saturday, June 11, 2016 at 4:30 p.m. CEST)

Outcomes for AML patients who are not candidates for intensive chemotherapy or allogeneic stem cell transplant are dismal. Low intensity treatment options, including HMAs (azacitidine and decitabine), are limited. Interim results from the first 25 patients in the ongoing phase 1 study evaluating 33A in combination with HMAs in frontline AML were presented at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. Updated interim results from the ongoing phase 1 study were presented in an oral session at EHA (Free EHA Whitepaper).

Data were reported from 53 frontline unfit AML patients with a median age of 75 years and intermediate or adverse cytogenetic risk who had declined intensive therapy. Forty-five percent of patients had evidence of underlying myelodysplasia. Key findings presented by Dr. Fathi include:

Of 49 efficacy-evaluable patients treated with 33A combined with either azacitidine or decitabine, the overall response rate was 76 percent. Complete remission (CR) or complete remission with incomplete platelet or neutrophil recovery (CRi) was observed in 35 patients (71 percent). The remission rate (CR+CRi) was similar between the two 33A and HMA combination treatment groups (71 percent combined with azacitidine and 72 percent combined with decitabine).
Responses were observed in higher-risk patients, with remissions achieved in 16 of 22 patients (73 percent) with underlying myelodysplasia and 15 of 18 patients (83 percent) with adverse cytogenetics.
Patients who achieved minimal residual disease included eight of 19 (42 percent) CR patients and five of 15 (33 percent) CRi patients.
The median overall survival for all patients in the phase 1 trial is interim and expected to evolve. The estimated median overall survival for the first 25 patients enrolled in the study was 12.75 months, with a median follow-up of 12.58 months.
Median relapse-free survival was 7.7 months (range, 0.0+ and 11.3+) with 27 patients (51 percent) remaining alive and on study as of last follow-up. The 30- and 60-day mortality rates were two and eight percent, respectively.
The most common treatment-related adverse events of any grade occurring in 20 percent or more of patients were fatigue (57 percent), thrombocytopenia (53 percent), nausea (49 percent), febrile neutropenia (45 percent), and constipation and anemia (42 percent each). The most common Grade 3 or 4 treatment-emergent adverse events occurring in 20 percent or more of patients were febrile neutropenia, thrombocytopenia, neutropenia, anemia and fatigue.
About Acute Myeloid Leukemia
Acute myeloid leukemia, also called acute myelocytic leukemia or AML, is an aggressive type of cancer of the bone marrow and blood that progresses rapidly without treatment. AML is a cancer that starts in the cells that are supposed to mature into different types of blood cells. AML starts in the bone marrow (the interior part of bones, where new blood cells are made) and quickly moves into the blood. According to the American Cancer Society, in 2016 approximately 20,000 new cases of AML (mostly in adults) will be diagnosed and nearly 10,500 deaths will occur from AML (almost all will be in adults).

About Vadastuximab Talirine (SGN-CD33A)
Vadastuximab talirine (SGN-CD33A; 33A) is a novel investigational ADC targeted to CD33 utilizing Seattle Genetics’ newest ADC technology. CD33 is expressed on most AML and MDS blast cells. The CD33 antibody is attached to a highly potent DNA binding agent, a pyrrolobenzodiazepine (PBD) dimer, via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the site-specific conjugation technology (EC-mAb) allows uniform drug-loading of the cell-killing PBD agent to the anti-CD33 antibody. The ADC is designed to be stable in the bloodstream and to release its potent DNA binding agent upon internalization into CD33-expressing cells.

33A was granted Orphan Drug Designation by both the U.S. Food and Drug Administration (FDA) and the European Commission for the treatment of AML. FDA orphan drug designation is intended to encourage companies to develop therapies for the treatment of diseases that affect fewer than 200,000 individuals in the United States.

On June 11, 2016 Boehringer Ingelheim reported that the results of the Phase III POLO-AML-2 trial investigating volasertib plus chemotherapy (low dose cytarabine, LDAC), in the treatment of elderly acute myeloid leukemia (AML) patients, did not meet the primary endpoint of objective response (Press release, Boehringer Ingelheim, JUN 11, 2016, View Source [SID:1234513209]). Boehringer Ingelheim is committed to further investigating volasertib with a revised research strategy based on the learnings of the trial, which demonstrated the compound’s anti-leukemic activity and an increased response rate.

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The results, presented at the 21st Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) 2016, showed the percentage of patients with an objective response was higher with volasertib plus LDAC, compared to placebo plus LDAC, but the difference was statistically not significant. The data showed an unfavorable overall survival trend for the experimental treatment arm, with the safety profile of the volasertib plus LDAC dosing regimen considered as the main reason for the trend.

Martin Stefanic, Medical Head, Early Clinical Development, Boehringer Ingelheim commented: "We are disappointed with the findings of the POLO-AML-2 trial after the encouraging results we observed in the Phase II trial. However, we believe in the potential of volasertib and new clinical studies have been initiated for AML patients, in addition to other areas of high unmet need such as higher risk myelodysplastic syndromes (MDS). The goal of these studies is to improve tolerability with modified dosing and scheduling of volasertib, while not compromising on efficacy, in order to achieve the best outcome for patients."

POLO-AML-2 (NCT01721876) is a randomized, double-blind, multi-center, controlled Phase III clinical trial of volasertib in combination with LDAC in 666 patients aged 65 years and older with newly diagnosed AML, not suitable for intensive induction therapy. The primary analysis showed a higher number of patients responded to volasertib plus LDAC (25.2%) than placebo plus LDAC (16.8%) but the overall result was not statistically significant.

There was a higher incidence of severe adverse events with volasertib plus LDAC, with a fatal infection frequency of 16.6% (volasertib plus LDAC) vs 5.1% (placebo plus LDAC) which was considered the main reason for a negative overall survival trend in the volasertib plus LDAC treatment arm compared to placebo plus LDAC (primary OS analysis: HR 1.26 [95% CI 0.95–1.67; p=0.113]; updated OS analysis (Nov 2015): HR 1.06 [95% CI 0.88–1.28; p=0.552]). The unblinded trial is still ongoing and updated results will be presented at a future scientific meeting when they are available.

Boehringer Ingelheim has a substantial program in hematological cancers with five investigational compounds in early clinical development.

About volasertib
Volasertib is an investigational compound that inhibits enzymes called Polo-like kinases (PLKs). Inhibition of PLK1 by volasertib ultimately results in cell death (apoptosis). By inhibiting PLK1 activity, the extremely high cell division that is characteristic of AML should be blocked, which may result in cancer regression.