On June 5, 2017 Abbvie reported that long-term follow-up results from the pivotal Phase 3 RESONATE trial (PCYC-1112) showed continued survival rates in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) treated with IMBRUVICA (ibrutinib) up to four years, according to new data were presented today at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago (poster session: 8:00 a.m. – 11:30 a.m. CDT; poster discussion: 1:15 p.m. – 2:30 p.m. CDT) (Press release, AbbVie, JUN 5, 2017, View Source [SID1234519415]). The data regarding IMBRUVICA, a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor and the first chemotherapy-free treatment for patients with CLL, were announced by AbbVie (NYSE: ABBV), a global biopharmaceutical company. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.

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According to the study results, IMBRUVICA was associated with significantly longer progression free survival (PFS; 59 percent) in R/R CLL/SLL with median follow-up of 44 months, including in patient subgroups with genomic abnormalities that are traditionally considered high-risk for poor outcomes. In addition, 3-year overall survival (OS; 74 percent) was longer in IMBRUVICA-treated patients. Further, the overall response rate (ORR) was 91 percent with complete response (CR) rates increasing over time (9 percent) (abstract #7510).1

"These results suggest ibrutinib continues to provide persistent responses over the long-term in patients with chronic lymphocytic leukemia, including those who are difficult to treat," said John C. Byrd, MD, Distinguished University Professor at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and lead investigator of the study.* "As a clinician who has treated patients with CLL for more than 20 years, I’m pleased to see the potential for efficacy and safety responses to continue over an extended period of time."

CLL, the most common form of leukemia in adults, is a type of cancer that starts from cells that become certain white blood cells (called lymphocytes) in the bone marrow. The cancer (leukemia) cells start in the bone marrow but then spread into the blood. There are more than 20,000 newly diagnosed CLL patients every year.2 CLL is predominately a disease of the elderly, with a median age of 71 at diagnosis.2 SLL is similar to CLL and affects the same lymphocytes; the only difference between the two is the location where the cancer primarily occurs.3 To-date, more than 25,000 CLL patients have been treated in the U.S. with IMBRUVICA since approval in 2014.

"The first pivotal RESONATE data on IMBRUVICA were presented three years ago at ASCO (Free ASCO Whitepaper) and represented the promise of a new standard of care in blood cancer treatment. We are pleased to continue to see very favorable responses and survival outcomes to IMBRUVICA in relapsed and refractory CLL patients now into the fourth year of study," said Danelle James, M.D., M.S., Head of Clinical Science, Pharmacyclics LLC, an AbbVie company. "We believe in the potential of IMBRUVICA across a range of blood cancers and other serious diseases, and are continuing to explore its potential as part of our robust clinical research program."

About the Study

Abstract #7510: Long-term efficacy and safety with ibrutinib (ibr) in previously treated chronic lymphocytic leukemia (CLL): Up to four years follow-up of the RESONATE study (Poster Board: #272)

Poster Session on Monday, June 5, 2017, 8:00 a.m. – 11:30 a.m. CDT at Hall A
Poster Discussion on Monday, June 5, 2017, 1:15 p.m. – 2:30 p.m. CDT at E354b
At up to 4 years of follow up, PFS was significantly longer for IMBRUVICA than ofatumumab (median NR versus 8 months, [HR 0.133; P<0.0001]; 3-year PFS 59 percent versus 3 percent). Significant benefit was observed across patient subgroups with genomic abnormalities that are traditionally considered high-risk for poor outcomes. Specifically, the high-risk genomic abnormalities were deletion 11q (del 11q), deletion 17p (del 17p), complex karyotype (CK), unmutated immunoglobulin heavy-chain variable-region (IGHV), NOTCH1 mutation, TP53 mutation, SF3B1 mutation, BIRC3 mutation and XP01 mutation. Patients with del 11q trended to have the most favorable outcome; however, PFS was not statistically different for patients with del 17p or del 11q or without these FISH abnormalities. At analysis, with the majority of patients (68 percent) randomized to ofatumumab crossing over to IMBRUVICA, OS was longer for IMBRUVICA versus ofatumumab (median OS not reached for either arm). The OS rate for IMBRUVICA at 3 years was 74 percent, and ORR was 91 percent, with CR and incomplete bone marrow recovery (CRi) increasing over time (now 9 percent).1

RESONATE is a Pharmacyclics-sponsored, randomized, multi-center, open-label, international Phase 3 study, which enrolled 391 patients with R/R CLL/SLL who had received at least one prior therapy and were not considered appropriate candidates for treatment with a purine analog (median age 67). Patients were administered either 420 mg oral IMBRUVICA (n=195) once-daily until progression or unacceptable toxicity or intravenous ofatumumab for up to 24 weeks (n=196, initial dose of 300 mg followed by 11 doses at 2,000 mg per dose and schedule consistent with local labeling). The study met its primary endpoint, demonstrating improved PFS.1

The adverse event (AE) profile of IMBRUVICA was consistent with previous reports. Major hemorrhage, Grade ≥3 atrial fibrillation, and Grade ≥3 hypertension occurred in 6 percent, 6 percent, and 8 percent of patients, respectively, over a follow-up of up to 4 years. The incidence of most Grade ≥3 AEs decreased from year 1 versus year 2-3: neutropenia (18 percent versus 8 percent); pneumonia (11 percent versus 4 percent); atrial fibrillation (4 percent versus 2 percent), respectively. Discontinuations were most frequently due to progressive disease (27 percent) and AEs (12 percent). At analysis, 90 IMBRUVICA patients (46 percent) continue on therapy in the study.1

About IMBRUVICA
IMBRUVICA (ibrutinib) 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 FDA-approved in five distinct patient populations: CLL, SLL, Waldenström’s macroglobulinemia (WM), along with previously-treated mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL).4

IMBRUVICA was first approved for patients with MCL who have received at least one prior therapy in November 2013.
Soon after, IMBRUVICA was initially approved in CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
IMBRUVICA was approved for patients with WM in January 2015.
In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for CLL/SLL patients.
In January 2017, IMBRUVICA was approved for patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.
Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description 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. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA has been granted four Breakthrough Therapy Designations from the FDA, spanning CLL/SLL, WM, MCL and chronic graft-versus-host-disease (cGVHD). In addition, IMBRUVICA is the first standard therapy specifically approved for patients with previously-treated MZL and WM.

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 approximately 130 ongoing clinical trials. There are a total of 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and approximately 100 investigator-sponsored trials and external collaborations that are active around the world. To date, 70,000 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) and Pneumocystis jirovecii pneumonia (PJP) 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, 13% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 13%) 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, 3% 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, 2% 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. Advise men to avoid fathering a child during the same time period.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia** (61%), thrombocytopenia** (62%), diarrhea (43%), anemia** (41%), musculoskeletal pain (30%), rash (30%), nausea (29%), bruising (30%), fatigue (29%), hemorrhage (22%), 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%).

The most common Grade 3 or 4 non-hematologic adverse reactions (≥5%) in MZL patients were pneumonia (10%), fatigue (6%), diarrhea (5%), rash (5%), and hypertension (5%).

Approximately 6% (CLL/SLL), 14% (MCL), 11% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4%-10% (CLL/SLL), 9% (MCL), and 9% (WM [6%] and MZL [13%]) of patients discontinued due to adverse reactions. Most common adverse reactions leading to discontinuation were pneumonia, hemorrhage, atrial fibrillation, rash, and neutropenia (1% each) in CLL/SLL patients and subdural hematoma (1.8%) in MCL patients. The most common adverse reactions leading to discontinuation were interstitial lung disease, diarrhea, and rash (1.6% each) in WM and MZL 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 June 5, 2017 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported safety and efficacy data from an ongoing phase 1/2a study of the anti-CD38 antibody MOR202 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2017 Annual Meeting in Chicago (Press release, MorphoSys, JUN 5, 2017, View Source [SID1234519413]). The dose escalation trial comprises three arms: MOR202, MOR202 in combination with the immunomodulatory drug (IMiD) lenalidomide (LEN) and MOR202 in combination with the IMiD pomalidomide (POM), in each case with low-dose dexamethasone (DEX). The trial is being conducted in heavily pre-treated patients with relapsed/refractory multiple myeloma.

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"Antibodies directed against CD38 have been reported as a class of potential therapeutics for patients with relapsed or refractory multiple myeloma. Based on the maturing data generated for MOR202, we will intensify our evaluations to further develop this compound as a representative of this class," commented Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "We are optimistic about the responses seen in patients treated with MOR202 plus LEN/DEX and POM/DEX as well as the relatively short infusion time and the occurrence of infusion-related reactions in a low proportion of patients observed. We look forward to results further maturing from patients treated in this ongoing trial and to presenting final data later this year."

MOR202 was given as a 2-hour infusion up to the highest dose of 16 mg/kg. Infusion-related reactions (IRRs) occurred in 6% of patients in the clinically relevant dose cohorts of MOR202 (4 mg/kg, 8 mg/kg, 16 mg/kg) and were limited to grade 1 or 2. The most frequent adverse events of grade 3 or higher were neutropenia, lymphopenia, and leukopenia in 42%, 40%, and 33% of patients respectively. No unexpected safety signals were observed.

Patients treated with MOR202 in combination with LEN/DEX had a median of three prior treatment regimens, 56% being refractory to at least one prior therapy. Median progression-free survival (PFS) was not yet reached, median follow-up was 7.5 months and 9 patients were still on study at data cut-off. 12 out of 17 patients (71%, based on the ITT population) reported an objective response (OR) to treatment, including one complete remission (CR), three very good partial responses (VGPR) and eight partial responses (PR).

Patients receiving MOR202 with POM/DEX, had a median of four prior treatment regimens, all being refractory to at least one prior therapy. Current median PFS is 17.5 months, with a median follow-up of 8.5 months. Eight patients were still on study at data cut-off. 6 out of 13 patients (46%, based on the ITT-population) showed an objective response, with two patients achieving a complete remission (CR).

Patients treated with MOR202 plus DEX had a median of five prior treatment regimens before study entry. Median PFS of this cohort was 4.7 months, with a median follow-up of 22.1 months. 5 out of 18 patients (28%, based on the ITT population) had an objective response.

Details of the MOR202 presentation at ASCO (Free ASCO Whitepaper) 2017

Abstract #8024, poster board #350

MOR202 with low-dose dexamethasone (DEX) and in combination with pomalidomide/DEX and lenalidomide/DEX in relapsed or refractory multiple myeloma (RRMM): Interim analysis of a phase 1/2a dose-escalation study

The poster will be presented during the "Hematologic Malignancies – Plasma Cell Dyscrasia" session on June 5, 2017 (8:00 AM-11:30 AM CDT, poster hall).

MorphoSys will hold an Investor & Analyst Event at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting on June 5, 2017, at 6:30pm CDT (June 6, 2017: 1:30am CEST). Clinical data for MorphoSys’s investigational agents MOR208 and MOR202 will be presented by clinical investigators and company representatives.

A replay and the presentation will be made available at View Source

Live-Webcast: https://services.choruscall.com/dataconf/productusers/morph/mediaframe/19794/indexl.html

About MOR202 and the ongoing phase 1/2a study in multiple myeloma
The investigational drug MOR202 is a fully human HuCAL antibody directed against CD38, a highly expressed and validated target in multiple myeloma. Data are from an ongoing clinical phase 1/2a, open-label, multi-center, dose-escalation study conducted in several sites in Germany and Austria. The study is evaluating the safety and preliminary efficacy of MOR202 with low dose dexamethasone and in combination with the immunomodulatory drugs (IMiDs) pomalidomide (POM) and lenalidomide (LEN) plus DEX in patients with relapsed/refractory multiple myeloma. The primary endpoints of the trial are the safety, tolerability and recommended dose of MOR202 with DEX and in combination with the IMiDs. Secondary outcome measures are pharmacokinetics and preliminary efficacy based on overall response rate, duration of response, time-to-progression, and progression-free survival.

On June 5, 2017 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number: 4875), reported that Associate Professor Kerrie McDonald, Head of the Cure Brain Cancer Foundation Biomarkers and Translational Research Group at the Lowy Cancer Research Centre, University of New South Wales, today presented positive results from an animal model study that examined the potential clinical efficacy of MN-166 (ibudilast) for the treatment of glioblastoma at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 5th , 2017 in Chicago, Illinois (Press release, MediciNova, JUN 5, 2017, View Source [SID1234519412]).

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Major highlights of the presentation titled "Treating glioblastoma with a cytokine inhibitor, ibudilast in combination with temozolomide extends survival in a patient derived xenograft model," are summarized as follows:

Tumor samples from glioblastoma (GBM) patients, divided into two groups according to overall survival (i.e., "poor survivors" were defined by survival of less than 12 months and "good survivors" were defined by survival of more than 12 months) were examined for protein overexpression.
Proteomics analysis in frozen GBM tissues identified Macrophage Migration Inhibitory Factor (MIF) overexpression in the cells from "poor survivors;"
Among 168 GBM patient-derived tumor tissue samples, MIF and its receptor CD-74 were significantly over-expressed in 57% of patients and were found to be associated with poor survival.
A mouse model of GBM was developed by using patient-derived GBM cells and treated with temozolomide (TMZ) (10mg/kg) alone and combination with ibudilast (5mg/kg or 20mg/kg). Findings from this mouse model included the following:

Median survival for the group that received TMZ treatment-only increased by 5 days (105.5 days p=0.054) compared to the control group;
Median survival for the group that received combination treatment of ibudilast (5mg/kg or 20mg/kg) with TMZ increased by 13.5 days and 11 days, respectively (114 days and 111.5 days, respectively, (p=0.005)), compared to the control group.
Median survival for the control group (i.e., no treatment) was 100.5 days.
Significant synergism between ibudilast and TMZ was observed.
MediciNova is currently preparing to initiate a Phase 2 clinical trial for the treatment of recurrent Grade IV glioblastoma with University of Sydney Royal North Shore Hospital.

About Glioblastoma

Malignant primary brain tumors represent the most frequent cause of cancer death in children and young adults and account for more deaths than melanoma. According to the American Association of Neurological Surgeons, glioblastoma (GBM) is an aggressive, extremely lethal form of brain malignancy that develops from glial cells (astrocytes and oligodendrocytes) and rapidly grows and commonly spreads into nearby brain tissue. GBM is classified as Grade IV, the highest grade, in the World Health Organization (WHO) brain tumor grading system. The American Brain Tumor Association reports that GBM represents 15% of all brain tumors and 55% of all gliomas and has the highest number of cases of all malignant tumors, with an estimated 12,390 new cases predicted for 2017. Despite decades of advancements in neuroimaging, neurosurgery, chemotherapy, and radiation therapy, only modest improvements have been achieved and the prognosis has not improved for individuals diagnosed with GBM. Median survival is 14.6 months and only approximately 5% of GBM patients survive longer than 36 months.

About MN-166 (ibudilast)

MN-166 (ibudilast) has been marketed in Japan and Korea since 1989 to treat post-stroke complications and bronchial asthma. MediciNova is developing MN-166 for progressive MS and other neurological conditions such as ALS and drug use disorders. MN-166 (ibudilast) is a first-in-class, orally bioavailable, small molecule phosphodiesterase (PDE) -4 and -10 inhibitor and a macrophage migration inhibitory factor (MIF) inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. It attenuates activated glia cells, which play a major role in certain neurological conditions. Ibudilast’s anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical study results and provide the rationale for its therapeutic utility in neurodegenerative diseases (e.g., progressive MS and amyotrophic lateral sclerosis [ALS], also known as Lou Gehrig’s disease), substance abuse/addiction and chronic neuropathic pain.

On June 5, 2017 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by advancing its proprietary R&D pipeline and manufacturing high quality products for biotechnology and pharmaceutical companies, reported the presentation of promising new data from its Phase III SUNRISE trial of bavituximab in patients with previously treated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) (Press release, Peregrine Pharmaceuticals, JUN 5, 2017, View Source [SID1234519407]). Presented results demonstrated that patients in the study’s bavituximab treatment arm who had low baseline PD-L1 expression levels had a statistically significant improvement in median overall survival (mOS) as compared to patients in the same treatment arm who had higher baseline levels of PD-L1. Data were presented by Peregrine scientists at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), being held June 2 – 6, 2017 in Chicago.

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Data presented demonstrated that patients in the study’s docetaxel plus bavituximab (D+B) treatment arm with a pre-treatment PD-L1 expression level on tumor cells of < 1% (TC0) had a mOS of 12.1 months compared to a mOS of 6.1 months for patients with PD-L1 expression ≥1% (TC1/2/3) (HR = 0.42 p=0.007). There was no difference in mOS based on PD-L1 expression levels observed in the study’s docetaxel plus placebo (D+P) control arm (10.7 months for TC0 vs. 11.1 months for TC1/2/3; HR = 0.87; p=0.609).

"We believe that these latest observations from the SUNRISE trial further support the hypothesis that bavituximab, through its immune modulating mechanism, may have more effect on tumors without pre-existent immunity. These ‘cold’ tumors suppress normal anti-tumor immune response and are categorized by very low to no PD-L1 expression on tumor cells," said Joseph Shan, vice president of clinical and regulatory affairs at Peregrine. "These latest findings, along with other recently announced clinical and preclinical data from our PS-targeting program, inform our clinical development strategy going forward and provide additional rationale for combining bavituximab with checkpoint inhibitors."

As part of the SUNRISE clinical study protocol, researchers requested but did not require that patients provide a tumor tissue sample at the time of diagnosis. In total, tissue samples were collected from 129 of the trial’s 597 patients and were assessed retrospectively for baseline PD-L1 expression levels on tumor cells. Of the 129 tissue samples collected, 122 were evaluable for PD-L1 expression on tumor cells (54 in D+B arm and 68 in D+P control arm). Of the evaluable samples in the D+B arm, 69% demonstrated PD-L1 expression levels < 1%, as compared to 59% in the D+P arm.

Bavituximab is an investigational immune-modulatory monoclonal antibody that targets phosphatidylserine (PS). PS inhibits the ability of immune cells to recognize and fight tumors. Bavituximab is believed to reverse PS-mediated immunosuppression by blocking the engagement of PS with its receptors as well as by sending an alternate immune activating signal. PS-targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor immune responses.

Peregrine’s clinical development strategy for bavituximab currently focuses on small, early-stage, proof-of-concept trials evaluating the drug in combination with other cancer treatments. This approach includes grants awarded by the National Comprehensive Cancer Network (NCCN) to support three different clinical trials of bavituximab treatment combinations. These trials will evaluate novel bavituximab combinations in glioblastoma, head and neck cancer, and hepatocellular carcinoma including an immunotherapy combination. Additionally, Peregrine continues to advance its pre-clinical collaboration with Memorial Sloan Kettering Cancer Center (MSK) with the goal of evaluating combinations of PS targeting antibodies with checkpoint inhibitors and other immune stimulatory agents. Peregrine’s intent behind this strategy is to focus its research and development spending to further validate bavituximab’s combination potential as the company seeks to advance the program though a pharmaceutical or biotechnology partner.

On June 5, 2017 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel small molecule drug candidates to treat cancer, with a primary focus on Myelodysplastic Syndromes (MDS), reported the results of a Phase 2 study with rigosertib as a treatment for higher risk (HR-MDS) after failure of hypomethylating agents (HMAs) (Press release, Onconova, JUN 5, 2017, View Source [SID1234519406]). The study sought to evaluate bone marrow blast (BMBL) response to rigosertib as a surrogate for overall survival (OS) in this patient population. The results showed treatment with rigosertib resulted in a reduction in BMBL count, including complete bone marrow responses, confirming findings in earlier studies. Thus, BMBL response to rigosertib is a potential surrogate marker for improvement in overall survival in this patient population.

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"In this new study for HR-MDS patients after failure of HMA therapy, we are excited to confirm a correlation between blast reduction and prolongation of survival in rigosertib treated patients. These results build upon our previous findings in the ONTIME trial showing improvement in overall survival in patients with the highest risk prognostic categories after failure of HMA treatment (ASH 2014 presentation),"said Ramesh Kumar, Ph.D., President and CEO of Onconova.

Rigosertib is currently being tested in a randomized, global, Phase 3 INSPIRE trial for this patient population.

Study Name: Relationship of Bone Marrow Blast response to Overall Survival in a Multicenter Study of Rigosertib in Patients with Myelodysplastic Syndromes with Excess Blasts Progressing on or After Treatment with a Hypomethylating Agent

Summary of Data from the 04-24 Trial

Patient Demographics:

64 patients treated, with a median age of 73, median prior HMA duration of 10.8 months.
Eligible patients had 5%-30% BMBL confirmed within six weeks pre-study and disease. progression as per International Working Group (IWG) 2006 criteria, Cheson et al., Blood 2006) on or after HMAs within two years.
Safety/Tolerability:

Intravenous rigosertib has been well tolerated to date.
More than 1,100 patients have been treated with rigosertib.
Adverse events in study 04-24 were similar to those observed in the preceding Phase 3 ONTIME Study
Objectives:

Primary Efficacy: Evaluate the relationship between BMBL response and OS in MDS patients with excess blasts (5-30%) progressing on or after treatment with azacitidine or decitabine who are administered 72-hr continuous intravenous (IV) infusions of 1800 mg/24 hour rigosertib every 2 weeks for 8 cycles and every 4 weeks thereafter. BMBL response is defined according to the International Working Group (IWG) 2006 criteria; or stable BM response (no progression),
Secondary Efficacy: Evaluate the following parameters: Overall response (CR, partial response/remission [PR], BMCR, and stable disease [SD]) according to 2006 IWG criteria; Population pharmacokinetics.
Safety: safety and tolerability of rigosertib administered as 72-hour continuous IV (5%-30% BMBL) progressing on or after treatment with azacitidine or decitabine.
Trial Design:

Phase 2 open-label, multi-center multi-national study (approximately 30-40 Centers in the US and Europe) of the efficacy and safety of Rigosertib administered as 72-hour continuous intravenous infusions in patients with myelodysplastic syndromes with excess blasts progressing on or after treatment with azacitidine or decitabine.
Treatment will continue until IWG 2006 progression criteria are met (ie, 50% increase of BMBL or worsening of cytopenias) or until death from any cause, whichever comes first.
Following these results, all patients will be followed until death and/or progression, even if they have discontinued treatment for any reason. View the complete study poster HERE.