On December 6, 2015 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported the presentation of results from a Washington University-sponsored Phase 1 trial of vosaroxin plus azacitidine in patients with myelodysplastic syndrome, and from an analysis of the Company’s Phase 3 VALOR trial of vosaroxin and cytarabine in relapsed/refractory acute myeloid leukemia (AML) at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, Florida (Press release, Sunesis, DEC 6, 2015, View Source;p=RssLanding&cat=news&id=2120408 [SID:1234508433]). The posters, titled "A Phase I Study of Vosaroxin plus Azacitidine for Patients with Myelodysplastic Syndrome" (publication number 1686) and "Baseline Predictors of Mortality in Patients with Relapsed or Refractory Acute Myeloid Leukemia Treated with Vosaroxin Plus Cytarabine or Placebo plus Cytarabine in the Phase 3 VALOR Study" (publication number 2560) are available at www.sunesis.com.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A Phase I Study of Vosaroxin Plus Azacitidine for Patients with Myelodysplastic Syndrome

In a Phase 1/2, open label, dose-escalation trial sponsored by the Washington University School of Medicine, patients with MDS who may have received up to three prior cycles of hypomethylating agent-based therapy were given vosaroxin and azacitidine for a maximum of six cycles. The Phase 1 portion of the study was designed to determine the maximum tolerated dose and dose limiting toxicity of the combination. Other endpoints include best response, safety, tolerability, and event-free, progression-free, disease-free and overall survival.

Thirteen patients were enrolled in the dose-escalation phase and five of twenty planned patients have been enrolled in the expansion cohort to date. At the initial dose of 50 mg/m2/day vosaroxin, 2 of 6 patients experienced a DLT (grade 4 hyperbilirubinemia, and grade 4 neutropenia >42 days). The vosaroxin dose was de-escalated to 34 mg/m2/day, resulting in 1 of 6 patients with a DLT (grade 4 mucositis). Of the 18 patients enrolled to date, 16 completed ≥1 cycle and are evaluable for response. Best response for each patient was as follows: stable disease, n=3; stable disease with hematologic improvement (HI)-neutrophils, n=2; marrow complete remission (CR), n=4; marrow CR with HI-platelets; n=2; marrow CR with HI-neutrophils, n=1; marrow CR with HI-erythroid, n=1; and marrow CR with HI-platelets and neutrophils, n=1; and CR, n=1. One patient had progressive disease (PD). Of the 16 evaluable patients, 6 have proceeded to allogenic stem cell transplant and 3 are actively undergoing study treatment. The major non-hematologic toxicities of febrile neutropenia, infections, and mucositis were expected based on the disease population and prior experiences with vosaroxin.

"Hypomethlyating agents are the mainstay of treatment for myelodysplastic syndromes, yet these agents alone produce remissions in a minority of patients and are typically not curative," said Meagan A. Jacoby, M.D., Ph.D., Assistant Professor, Division of Oncology, Washington University School of Medicine, and principal investigator of the study. "The combination of vosaroxin and azacitidine show promising activity with response rates comparable or better than those generally observed with azacitidine alone. Additionally, the transplant rate observed is encouraging in this patient population with a median age of 66 years. We look forward to additional patient accrual and follow up from this study."

Baseline Predictors of Mortality in Patients with Relapsed or Refractory Acute Myeloid Leukemia Treated with Vosaroxin Plus Cytarabine or Placebo Plus Cytarabine in the Phase 3 VALOR Study

Treatment-related mortality (TRM) score is a prognostic scoring system to predict risk of 30-day mortality with intensive treatment protocols in patients with newly diagnosed AML (Walter, 2011, J Clin Oncol 29:4417-4424). The "simplified TRM" score includes age, performance status (PS), platelet count, serum albumin, type of AML (secondary vs primary), white blood cell count, blast percentage in the peripheral blood, and serum creatinine. In a retrospective analysis, TRM and other criteria were used to evaluate risk of early mortality in patients with relapsed or refractory acute myeloid leukemia treated with vosaroxin plus cytarabine or placebo plus cytarabine in Sunesis’ randomized, double-blind, placebo-controlled Phase 3 VALOR trial.

A total of 705 patients from VALOR were included in the safety population (355 treated with vosaroxin/cytarabine and 350 treated with placebo/cytarabine). Rates of 30-day (7.9% vs 6.6%, respectively) and 60-day (19.7% vs 19.4%, respectively) mortality in VALOR were comparable between vosaroxin plus cytarabine and placebo plus cytarabine arms. Several individual baseline factors independently predicted risk of early mortality, including ECOG performance status, hemoglobin, bilirubin and albumin levels, intermediate or high bone marrow blasts, and prior myelodysplastic syndrome. The previously validated TRM score for predicting early mortality in newly diagnosed AML was also predictive of mortality in this relapsed/refractory population. Vosaroxin/cytarabine treatment and age were not significant predictors of early mortality.

"The rate of early mortality in patients treated for acute myeloid leukemia reflects a balance of efficacy and safety outcomes," said Dr. Jeffrey Lancet, Senior Member and Professor of Oncologic Sciences at the H. Lee Moffitt Cancer Center, Tampa, Florida. "The ability to assess increased risk of early mortality in this disease would provide valuable information in guiding treatment decisions. Based on this analysis, patient selection for future studies of vosaroxin and other intensive regimens in the AML setting may benefit from use of these predictive factors."

About QINPREZO (vosaroxin)
QINPREZO (vosaroxin) is an anti-cancer quinolone derivative (AQD), a class of compounds that has not been used previously for the treatment of cancer. Preclinical data demonstrate that vosaroxin both intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site-selective DNA damage, G2 arrest and apoptosis. Both the U.S. Food and Drug Administration (FDA) and European Commission have granted orphan drug designation to vosaroxin for the treatment of AML. Additionally, vosaroxin has been granted fast track designation by the FDA for the potential treatment of relapsed or refractory AML in combination with cytarabine. Vosaroxin is an investigational drug that has not been approved for use in any jurisdiction.
The trademark name QINPREZO is conditionally accepted by the FDA and the EMA as the proprietary name for the vosaroxin drug product candidate.

On December 6, 2015 Seattle Genetics, Inc. (Nasdaq: SGEN) reported clinical data with denintuzumab mafodotin (SGN-CD19A; 19A) in B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL) and B-lineage acute lymphocytic leukemia (B-ALL), presented at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place in Orlando, Florida, December 5-8, 2015 (Press release, Seattle Genetics, DEC 6, 2015, View Source;p=RssLanding&cat=news&id=2120410 [SID:1234508431]). Preclinical data from a novel antibody-drug conjugate (ADC) program called SGN-CD19B in B-cell malignancies will also be featured in an oral presentation. About 85 percent of non-Hodgkin lymphomas (NHL) are B-cell lineage, and CD19 is broadly expressed across all subtypes of B-cell malignancies. These two ADCs, 19A and SGN-CD19B, both target CD19 and utilize two of Seattle Genetics’ proprietary payloads, monomethyl auristatin F (MMAF) and a pyrrolobenzodiazepine (PBD) dimer, respectively. The company has initiated the first of two planned phase 2 trials of 19A in DLBCL and plans to advance SGN-CD19B into a phase 1 trial in 2016.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Data presented at ASH (Free ASH Whitepaper) from our 19A phase 1 trial in non-Hodgkin lymphoma show encouraging objective response rates, particularly in relapsed DLBCL patients, and a tolerability profile that we believe supports further investigation as part of novel regimens. Based on these data, we recently initiated a phase 2 trial in relapsed DLBCL, and plan to initiate a phase 2 trial in frontline DLBCL during 2016," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "CD19 is an attractive target for NHL, and there is a clear need for potent, safe and convenient therapies that can be used to improve outcomes for patients."

With more than 15 years of experience and innovation, Seattle Genetics is the leader in developing ADCs, a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. More than 25 ADCs in clinical development utilize Seattle Genetics’ proprietary ADC technology.

A Phase 1 Study of Denintuzumab Mafodotin (SGN-CD19A) in Relapsed/Refractory B-Lineage Non-Hodgkin Lymphoma (Abstract #182, oral presentation on Sunday, December 6, 2015 at 7:45 a.m.)

Data were reported from 62 patients with relapsed or refractory NHL, including 54 patients with DLBCL, five patients with mantle cell lymphoma and three patients with grade 3 follicular lymphoma. Of the 62 patients, 37 patients (60 percent) were refractory to their last therapy and 25 patients (40 percent) were relapsed. Sixteen patients (26 percent) had received a prior autologous stem cell transplant. The median age of patients was 65 years.

The primary endpoints of the ongoing clinical trial are to estimate the maximum tolerated dose and evaluate the safety and tolerability of 19A. In addition, the trial is evaluating antitumor activity, pharmacokinetics, progression-free survival and overall survival. In this study, patients receive 19A either every three weeks or every six weeks. Patients with stable disease or better are eligible to continue treatment with 19A. Key findings from an oral presentation by Craig Moskowitz, M.D. Clinical Director, Division of Hematologic Oncology, Memorial Sloan Kettering Cancer Center, include:

The maximum tolerated dose was not exceeded after escalating to 6 milligrams per kilogram (mg/kg) every three weeks.
Of the 60 patients evaluable for response, 23 patients (38 percent) achieved an objective response, including 14 patients (23 percent) with a complete remission and nine patients (15 percent) with a partial remission. Thirteen patients (22 percent) achieved stable disease and 24 patients (40 percent) had disease progression.

Antitumor activity appeared to be higher in relapsed patients. Of the 25 relapsed patients, 15 patients (60 percent) achieved an objective response, including 10 patients (40 percent) with a complete remission. In the 23 relapsed patients who responded, median duration of response was 47.1 weeks. Among all relapsed patients, median progression-free survival was 25.1 weeks and median overall survival was 56.7 weeks.

The most common adverse events of any grade occurring in more than 15 percent of patients were blurred vision (63 percent); dry eye (53 percent); fatigue, keratopathy and photophobia (39 percent each). Ocular symptoms were reported in more than 70 percent of patients. Symptoms were mostly Grade 1/2 and were managed with steroid eye drop treatment and dose modifications. Eighty-eight percent of patients with Grade 3 or 4 keratopathy experienced improvement and/or resolution within a median of five weeks.

A Phase 1 Study of Denintuzumab Mafodotin (SGN-CD19A) in Adults with Relapsed or Refractory B-Lineage Acute Leukemia (B-ALL) and Highly Aggressive Lymphoma (Abstract #1328, poster presentation on Saturday, December 5, 2015)

Data were reported from 72 adult patients with relapsed or refractory B-ALL and highly aggressive lymphomas, including B-cell lymphoblastic lymphoma (B-LBL) and Burkitt lymphoma. The median age of adult patients was 45 years and the median number of prior systemic therapies was two, with 20 patients (28 percent) having received a prior allogeneic stem cell transplant.

The primary endpoints of the ongoing clinical trial are to estimate the maximum tolerated dose and to evaluate the safety of 19A. In addition, the trial is evaluating antitumor activity, pharmacokinetics, progression-free survival and overall survival. In this dose-escalation study, patients received 19A in Schedule A (40 patients) at 0.3 to 3 mg/kg weekly or Schedule B (32 patients) at 4 to 6 mg/kg every three weeks. Key findings include:

Of the 56 B-ALL adult patients evaluable for response, six patients (19 percent) treated weekly achieved a composite complete remission (complete remission or complete remission with incomplete platelet or blood recovery) and nine patients (38 percent) treated every three weeks achieved a composite complete remission. The median duration of response was 27 weeks. Fifty-four percent of patients across both schedules achieved cytoreduction of greater than 50 percent.

In the ten patients with Philadelphia chromosome positive (Ph+) B-ALL, five patients (50 percent) achieved a complete remission and one patient (10 percent) had a partial remission. Ph+ B-ALL represents 20 to 30 percent of adult patients and carries a dismal prognosis, with higher rates of relapse and lower overall survival.

The maximum tolerated dose was not reached in patients treated weekly and was identified at 5 mg/kg in patients treated every three weeks.

The most common adverse events of any grade occurring in 25 percent or more of patients treated weekly (40 patients) or every three weeks (32 patients), respectively, were nausea (63 and 41 percent), fatigue (58 and 47 percent), fever (55 and 50 percent), headache (45 and 38 percent) and anemia (43 and 22 percent).

In the study, 43 patients (60 percent) developed ocular symptoms, of which 91 percent were Grade 1/2. These included blurred vision (39 percent), dry eye (25 percent) and photophobia (19 percent). Ocular symptoms were managed with steroid eye drop treatment and dose modifications. Keratopathy was observed in 34 patients, of whom 22 patients had Grade 3/4 events. The majority of patients with Grade 3/4 events had improvement or resolution with a median time of approximately four weeks.
The 19A phase 1 clinical trials are ongoing. Separately, a randomized phase 2 trial has recently initiated evaluating 19A in combination with R-ICE chemotherapy for second-line DLBCL. In addition, a phase 2 clinical trial in frontline DLBCL is planned to begin in 2016. More information about the 19A clinical trials, including enrolling centers, is available by visiting www.clinicaltrials.gov.

SGN-CD19B, a Pyrrolobenzodiazepine (PBD)-Based Anti-CD19 Drug Conjugate, Demonstrates Potent Preclinical Activity Against B-Cell Malignancies (Abstract #594, oral presentation on Monday, December 7, 2015 at 11:45 a.m.)

A preclinical analysis evaluated the activity of SGN-CD19B, a new ADC consisting of an anti-CD19 antibody attached to a highly potent DNA binding agent called a PBD dimer, in multiple B-cell malignancy models. Data to be presented in an oral session demonstrate that SGN-CD19B exhibits antitumor activity against a broad panel of CD19-expressing B-cell malignancies, inducing durable tumor regressions and improved survival in multiple preclinical models of NHL and B-ALL. Based on these data, a phase 1 clinical trial evaluating SGN-CD19B in NHL is planned to start in 2016.

About Denintuzumab Mafodotin (SGN-CD19A)

Denintuzumab mafodotin (SGN-CD19A; 19A) is an ADC targeting CD19, a protein expressed broadly on B-cell malignancies. 19A is comprised of an anti-CD19 monoclonal antibody linked to a synthetic cell-killing agent, monomethyl auristatin F (MMAF). The ADC is designed to be stable in the bloodstream, and to release its cytotoxic agent upon internalization into CD19-expressing tumor cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing the antitumor activity.

About Non-Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and NHL. NHL is further categorized into indolent (low-grade) or aggressive, including DLBCL. DLBCL is the most common type of NHL. According to the American Cancer Society, more than 71,000 cases of NHL were to be diagnosed in the United States during 2015 and more than 19,000 people would die from the disease.

About Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia, also called acute lymphocytic leukemia or ALL, is an aggressive type of cancer of the bone marrow and blood that progresses rapidly without treatment. In ALL, lymphoblasts, which are malignant, immature white blood cells, multiply and crowd out normal cells in the bone marrow. ALL is the most common type of cancer in children. According to the American Cancer Society, more than 6,000 people will be diagnosed with ALL during 2015 and more than 1,400 would die from the disease.

On December 6, 2015 Novartis reported that findings from an ongoing Phase IIa study to evaluate the safety and efficacy of investigational chimeric antigen receptor T cell (CART) therapy CTL019 in certain types of relapsed or refractory (r/r) non-Hodgkin lymphoma will be presented in an oral session at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting (Press release, Novartis, DEC 6, 2015, View Source [SID:1234508429]). The study, conducted by the University of Pennsylvania’s Perelman School of Medicine (Penn), found an overall response rate (ORR) at three months of 47% (7/15) in adult patients with r/r diffuse large B-cell lymphoma (DLBCL) and an ORR of 73% (8/11) in adult patients with follicular lymphoma (FL) [1]. Results will be presented in an oral session at ASH (Free ASH Whitepaper) on Sunday, December 6 (Abstract #183, 8 a.m.) [1].

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These data add to the growing body of clinical evidence on CTL019 and illustrate its potential benefit in the treatment of relapsed and refractory non-Hodgkin lymphoma, a disease with few effective options," said lead investigator Stephen Schuster, M.D., Associate Professor, Division of Hematology/Oncology at the University of Pennsylvania, Abramson Cancer Center. "We look forward to continuing this study to further understand longer-term patient response."

The study findings include 26 adult patients (15 with DLBCL and 11 with FL) who were evaluable for response. The study found that three patients with DLBCL who achieved a partial response (PR) to treatment at three months converted to complete response (CR) by six months. In addition, three patients with FL who achieved a PR to treatment at three months converted to CR by six months. One DLBCL patient with a PR to treatment at three months experienced disease progression at six months after treatment. One FL patient with a PR to treatment at three months who remained in PR at nine months experienced disease progression at approximately 12 months after treatment. Median progression-free survival (PFS) was 11.9 months for patients with FL and 3.0 months for patients with DLBCL.

In the study, four patients developed cytokine release syndrome (CRS) of grade 3 or higher. CRS has been observed after CTL019 infusion when the engineered cells become activated and multiply in the patient’s body. During CRS, patients typically experience varying degrees of flu-like symptoms with high fevers, nausea, muscle pain, and in some cases, low blood pressure and breathing difficulties. Neurologic toxicity occurred in two patients, including one grade three episode of delirium and one possibly related grade five encephalopathy [1].

In contrast to typical small molecule or biologic therapies, CTL019 is specifically manufactured for each individual patient. A patient’s T cells are collected through a specialized blood draw called leukapheresis and then transferred to the Novartis manufacturing facility in Morris Plains, New Jersey. There the cells are reprogrammed to hunt cancer and other B-cells expressing CD19. The patient’s own modified cells are then transferred back to the treatment center where they are administered to the patient.

A poster presentation on December 6, 6-8 p.m., will report on how the successful transfer of cell processing technology from Penn to the Novartis cell manufacturing center in Morris Plains has enabled the scale-up of CTL019 production (Abstract #3100) [2]. The Morris Plains facility is the first FDA-approved Good Manufacturing Practices quality site for a cell therapy production in the US and is now processing cells to support ongoing Phase II multi-center global studies of CTL019 in specific leukemias and lymphomas.

"The company’s investment in our state-of-the-art manufacturing facility has given us the capacity and scalability needed to support our growing global clinical trial program," said Usman Azam, MD, Global Head, Cell & Gene Therapies Unit, Novartis Pharmaceuticals. "Novartis is proud to be the first healthcare company to initiate Phase II CART therapy trials in the US, Europe, Canada and Australia. This is a significant step forward in our mission to help address unmet medical needs of patients." A list of participating trial centers is available at View Source (link is external).

Because CTL019 is an investigational therapy, the safety and efficacy profile has not yet been established. Access to investigational therapies is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the therapy. Because of uncertainty of clinical trials, there is no guarantee that CTL019 will ever be commercially available anywhere in the world.

On December 6, 2015 Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, reported, in partnership with its collaborators, that clinical data from a chimeric antigen receptor (CAR) T cell product candidate, JCAR014, demonstrated encouraging clinical responses in patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Press release, Juno, DEC 6, 2015, View Source;p=RssLanding&cat=news&id=2120411 [SID:1234508428]). Results will be presented in an oral presentation today at the 54th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Orlando.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This Smart News Release features multimedia. View the full release here: View Source
In addition, a poster presentation highlighted clinical data from JCAR018, a CAR T cell product candidate targeting CD22 that demonstrated preliminary safety and clinical activity in pediatric and young adult r/r B-cell acute lymphoblastic leukemia (ALL) patients.

"Complete responses and the durability of those responses are key efficacy parameters in both NHL and CLL. The early data reported today are highly encouraging and suggest that our CD19-directed CAR T product candidates have the potential to have a meaningful impact for patients with these difficult-to-treat diseases," said Mark Frohlich, M.D., Executive Vice President, Development and Portfolio Strategy. "Our CD22-directed CAR T product candidate, JCAR018, has shown encouraging early signs of activity from the study in pediatric patients with r/r ALL, where CD19 epitope loss with treatment appears to be of increasing relevance. We look forward to more data in 2016 as we continue to treat patients at the current and higher dose levels."

In an oral presentation on Sunday, December 6, 2015, Cameron J. Turtle, MBBS, Ph.D. of the Fred Hutchinson Cancer Research Center will present "Anti-CD19 Chimeric Antigen Receptor-Modified T Cell Therapy for B Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Fludarabine and Cyclophosphamide Lymphodepletion Improves In Vivo Expansion and Persistence of CAR T Cells and Clinical Outcomes." Dr. Turtle will be updating results on a total of 41 patients treated with JCAR014 against B-cell malignancies.

Key Takeaways include:

JCAR014 (CD19-specific CAR T cells of defined subset composition) demonstrated potent anti-tumor activity and an acceptable toxicity profile in r/r adult B-cell NHL patients and CLL patients previously treated with ibrutinib.
A meaningful percentage of patients achieved a complete response in both r/r NHL and r/r CLL.

While longer follow-up is necessary to define full durability, there have been no relapses in NHL and CLL patients that achieved a complete response in this study with follow-up ranging from 2 to 14 months.

The addition of fludarabine and cyclophosphamide (flu/cy) lymphodepletion improved CAR T cell peak expansion, persistence and clinical outcomes in NHL.

Severe cytokine release syndrome and severe neurotoxicity were observed in some patients; lower doses of this defined cell product candidate appeared to correlate with lower rates of these toxicities.

In a poster presentation on Saturday, December 5, 2015, Terry J. Fry, M.D. of the Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, presented "Clinical Activity and Persistence of Anti-CD22 Chimeric Antigen Receptor in Children and Young Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)." Dr. Fry reported on a first-in-human anti-CD22 CAR T cell therapy (JCAR018) in pediatric and young adult r/r B-cell ALL. Key takeaways include:
JCAR018 provides a potential treatment alternative to patients with CD19 epitope loss variants, particularly relevant in pediatric ALL.

In this Phase I dose-escalation trial, nine patients have enrolled and seven patients have been assessed to date.
Six patients were treated with the lowest dose (3 x 105 cells/kg), with one patient reaching MRD-negative CR, two patients having stable disease, and three patients having disease progression.

Three patients have enrolled at the next dose (1 x 106 cells/kg), which is in the dose range of CD19-directed CAR T programs. One patient achieved an MRD-negative CR, and two patients are too early to assess for response.

One patient at the lowest dose had Grade 3 diarrhea, and the maximum cytokine release syndrome was Grade 2.

ASH Investor and Analyst Event and Webcast
The Juno ASH (Free ASH Whitepaper) Investor and Analyst Event and webcast will be held Monday, December 7, 2015 at 8:30p.m. Eastern Time. The webcast can be accessed live on the Investor Relations page of Juno’s website, www.JunoTherapeutics.com, and will be available for replay for 30 days following the event.

On December 6, 2015 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) reported an update on results from an investigator-sponsored Phase 2 trial of tosedostat – the company’s investigational oral selective aminopeptidase inhibitor – in elderly patients with either primary (de novo) acute myeloid leukemia (AML) or secondary AML (Press release, CTI BioPharma, DEC 6, 2015, View Source;p=RssLanding&cat=news&id=2120424 [SID:1234508427]). The data showed a complete response (CR) of 48.5 percent with tosedostat in combination with low dose cytarabine/Ara-C (LDAC) – 33 percent of these patients were still responding after a median of 506 days. Results were presented in an oral presentation by Dr. Giuseppe Visani, Director of Hematology and Stem Cell Transplant Center at AORMN, Pesaro, Italy at ASH (Free ASH Whitepaper) 2015 (Abstract#329).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

AML is the most common acute leukemia affecting adults, and its incidence increases with age while its treatment becomes increasingly unsatisfactory – particularly in patients over age 70 and in those with co-morbid conditions that increase the risk of intensive chemotherapy. New approaches that allow meaningful leukemic control with acceptable side effects are needed. In this study, treatment with tosedostat, added to conventional therapy with low dose cytarabine demonstrated a higher response rate and longer survival than would be expected by cytarabine alone. Of great interest, preliminary data using a gene array panel suggest that it might be possible to predict on the basis of a blood test, which patients are mostly likely to benefit from tosedostat.

"The additional findings from this Phase 2 study continue to show the potential for tosedostat in combination with LDAC to produce clinically meaningful results for a patient population that is in real need of additional treatment options," said Dr. Visani. "We look forward to performing a validation analysis to confirm the ability of this preliminary gene expression profiling for identifying potential responders to tosedostat, as we believe we have identified biomarkers where the achievement of these impression responses could be efficiently predicted."

"We are particularly excited about the preliminary results of the gene array panel in this study because being able to predict a patient’s likelihood of responding to tosedostat would help physicians personalize a patient’s treatment plan, potentially reducing unnecessary treatments and side effects with the goal of improving the overall patient experience," said James A. Bianco, M.D., President & CEO of CTI BioPharma. "These data support our commitment to moving the tosedostat development program forward in AML."

Additional Study Details
As previously reported, the study met the primary endpoint with an overall response rate (ORR) of 54.6 percent (n=18/33) in the intent-to-treat population (ITT). At ASH (Free ASH Whitepaper), the new findings presented showed – in patients receiving tosedostat in combination with LDAC – a CR rate of 48.5 percent (n=16/33) and that the median time for achieving best response was 74 days (range: 22-145 days) with 33 percent still in remission (or experiencing a CR) after a median follow-up of 506 days.

One of the secondary endpoints was to identify possible biomarkers associated with sensitivity and/or drug resistance. A gene expression profile (GEP) was performed on purified AML cells obtained from a subset of patients. Analysis of these patient cells identified a molecular signature associated with clinical response (CR vs. no CR). Based on the differentially expressed genes (n=212), samples were divided according to either CR or no CR. Results showed that these differentially expressed genes were associated with relevant biological functions and pathways – including B-catenin (beta-catenin), TNFA-NFkB, ERB2, inflammatory response, and epithelial-mesenchymal transition pathways – and suggested that the achievement of a CR could be efficiently predicted by GEP. A validation analysis is currently being conducted on additional patients in order to confirm the ability of GEP to identify potential responders to tosedostat.

Safety analysis show that tosedostat in combination with LDAC was generally well tolerated. The primary adverse events observed were pneumonitis (12 percent), cardiac (6 percent), brain hemorrhage (3 percent), and asthenia (3 percent).

About the Study Design
The Phase 2 multicenter clinical trial was designed to assess tosedostat (orally once-daily) in combination with intermittent LDAC (twice daily) in 33 elderly patients (median age = 75 years) with either primary AML or secondary AML. Courses of LDAC were repeated every four weeks for up to eight cycles in the absence of disease progression or unacceptable toxicity. The primary objective was to exceed the upper limit of institutional expected CR rates (P0=10%, P1= 25%, α=0.05, 1-β=80%); secondary objectives include safety and toxicity, stable disease, overall survival, and progression-free survival as well as the identification of a possible biomarker associated with sensitivity and/or disease resistance through global gene expression profiling (GEP, Affymetrix Transciptome Array 2.0).

About Tosedostat
Tosedostat is an oral aminopeptidase inhibitor that has demonstrated anti-tumor responses in blood-related cancers and solid tumors in Phase 1-2 clinical trials. Tosedostat is currently being evaluated in multiple Phase 2 clinical trials for the treatment of patients with AML or high-risk MDS, which are intended to inform the design of a Phase 3 registration study to support potential regulatory approval. Tosedostat is not approved or commercially available.

About Acute Myeloid Leukemia
AML is the most common acute leukemia affecting adults, and its incidence increases with age. In older patients, AML may occur de novo or secondary to prior anti-cancer therapy, or from progression of other diseases, such as myelodysplasia. AML is a cancer characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age.1 The symptoms of AML are caused by the replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets, and normal white blood cells, leading to infections and bleeding. AML progresses rapidly and is typically fatal within weeks or months if left untreated. In 2015, approximately 20,830 new cases of AML are expected to be diagnosed in the United States and an estimated 10,460 are expected to die from the disease.2 While AML may occur at any age, adults at least 60 years of age are more likely than younger people to develop the disease.2 Although a substantial proportion of younger individuals who develop AML can be cured, AML in the elderly typically responds poorly to standard therapy with few complete remissions.