On December 10, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported results from a phase Ib study of the investigational cancer immunotherapy atezolizumab (MPDL3280A) used in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (TNBC) (Press release, Hoffmann-La Roche , DEC 10, 2015, View Source [SID:1234508535]). The study showed that the combination shrank tumours (overall response rate, including unconfirmed responses) in 70.8% of people, [n=24; 95% confidence interval, (CI): 48.9, 87.4]. 11 of 17 responses (65%) continued on treatment at time of data cut-off. The highest overall response rate observed [88.9% (CI: 51.7, 99.7)] was in people receiving their initial (1st line) treatment for metastatic disease, with 1 confirmed complete responder. Responses were observed in both PD-L1 positive and PD-L1 negative patients. In addition, some patients with evidence of RECIST based progressive disease developed further response with continued treatment. Adverse events (AEs) were consistent with what has previously been reported for treatment of nab-paclitaxel alone, with 56% of patients (n=32) experiencing Grade 3–4 AEs. These data were presented at the San Antonio Breast Cancer Symposium 2015 congress.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!

"We are encouraged that a high proportion of people responded to combined treatment with atezolizumab and nab-paclitaxel chemotherapy, regardless of their PD-L1 expression," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "This result indicates that combinations may provide a way to increase the benefits of atezolizumab in a wide range of people with triple-negative breast cancer."

Based on these results and the observed activity of single-agent atezolizumab in these patients, Roche is evaluating the combination of atezolizumab and nab-paclitaxel in a phase III study (IMpassion130; NCT02425891) of patients with previously untreated metastatic TNBC.

About the phase Ib study of atezolizumab in combination with nab-paclitaxel

This part of the multicentre, multi-arm phase Ib study aimed to evaluate atezolizumab in combination with weekly nab-paclitaxel in patients with metastatic TNBC previously treated with systemic cytotoxic therapy

Primary endpoints were safety and tolerability, with secondary endpoints including efficacy using RECIST v1.1 criteria (best overall response, objective response rate, duration of response, progression-free survival), pharmacokinetics, as well as biomarker analyses
Patients received atezolizumab 800 mg once every 2 weeks (days 1 and 15) with nab-paclitaxel 125 mg/m2 weekly (days 1, 8 and 15) for 3 weeks in 4-week cycles, until loss of clinical benefit

All patients were women with a median age of 58 years (range 32–75 years)

PD-L1 expression was assessed for both tumour cells (TCs) and immune cells (ICs); people were scored as IC0, 1, 2 or 3 and TC0, 1, 2 or 3 with an immunohistochemistry (IHC) test being developed by Roche Tissue Diagnostics

Expression of PD-L1 in TNBC was mostly restricted to IC

Efficacy

Summary of Best Overall Responses by RECIST v1.1

Objective Response Rate by PD-L1 Expression Levela

Safety
Treatment-related Adverse Eventsa

AEs, adverse events
About triple-negative breast cancer
Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express oestrogen receptor (ER), progesterone receptor (PR) or overexpress the HER2 receptor. Approximately 10%–20% of all breast cancers are TNBC, and have a worse prognosis compared with other breast cancer subtypes.2, 3 TNBC is associated with more frequent recurrence, shorter disease-free interval and earlier visceral metastases. Patients with metastatic TNBC have decreased survival compared with patients with other subtypes of breast cancer, with a median survival of 6 to 13 months.4, 5, 6 Currently, chemotherapy is the mainstay of treatment for metastatic TNBC, although clinical practice patterns vary worldwide.

About atezolizumab
Atezolizumab (also known as MPDL3280A) is an investigational monoclonal antibody designed to target and bind to a protein called PD-L1, which is expressed on TCs and tumour-infiltrating ICs. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T-cells. By blocking this interaction, atezolizumab may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.

About Roche in cancer immunotherapy
For more than 30 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

About personalised cancer immunotherapy
The aim of personalised cancer immunotherapy (PCI) is to provide individual patients with treatment options that are tailored to their specific needs. Our PCI research and development programme comprises more than 20 investigational candidates, eight of which are in clinical trials. All studies include the prospective evaluation of biomarkers to determine which people may be appropriate candidates for our medicines. In the case of atezolizumab (also known as MPDL3280A), PCI begins with the PD-L1 (programmed death ligand-1) IHC assay based on the SP142 antibody developed by Roche Tissue Diagnostics. The goal of PD-L1 as a biomarker is to identify those people most likely to experience clinical benefit with atezolizumab as a single agent and which people may be appropriate candidates for combination therapies; the purpose is not to exclude patients from atezolizumab therapy, but rather to enable the design of combinations that will provide the greatest chance for transformative responses. The ability to combine atezolizumab with multiple chemotherapies may provide new treatment options to people across a broad range of tumours regardless of their level of PD-L1 expression.

On December 9, 2015 OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) reported that the independent Data Safety Monitoring Board (DSMB) at Dana-Farber/Harvard Cancer Center has recommended that the Phase 2 Borealis-2 trial continue as planned after completing the pre-specified futility analysis (Press release, OncoGenex Pharmaceuticals, DEC 9, 2015, View Source [SID:1234508509]).

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!

Borealis-2 is evaluating apatorsen in combination with docetaxel treatment in patients with metastatic bladder cancer. It is the third clinical trial assessing the ability of apatorsen to improve outcomes for patients in this tumor type. Previously, encouraging results were observed in the Borealis-1 trial evaluating apatorsen in combination with standard of care chemotherapy in metastatic bladder cancer, as well as a trial evaluating apatorsen as monotherapy in patients with non-muscle invasive (superficial) disease.

Investigators have concluded in the bladder cancer trials conducted to date that 600mg apatorsen administered intravenously and all apatorsen doses administered intravesically have been well tolerated. Clinical trials of apatorsen across four tumor types involving over 700 patients have been conducted or are currently ongoing with patient safety monitored throughout the course of these trials.

"We are pleased with the DSMB’s recommendation to continue the Borealis-2 trial and we look forward to final results expected in 2016," said Scott Cormack, President and Chief Executive Officer of OncoGenex. "Additionally, early next year we will receive regulatory feedback on our apatorsen clinical trial design and development strategy for patients with non-muscle invasive bladder cancer."

Borealis-2 is an investigator-sponsored, randomized Phase 2 trial evaluating a survival benefit with apatorsen in combination with docetaxel treatment compared to docetaxel treatment alone in approximately 200 patients with metastatic bladder cancer who have disease progression following first-line platinum-based chemotherapy. The trial is being coordinated by the Hoosier Cancer Research Network at 27 sites across the United States.

Upcoming Milestones
In addition to Borealis-2, OncoGenex expects to announce progression-free survival results for the Phase 2 Spruce trial in the first quarter of 2016 with continued overall survival follow up.

The company’s other asset, custirsen, is currently being evaluated in two ongoing Phase 3 clinical trials. The Phase 3 ENSPIRIT trial is evaluating the ability of custirsen, in combination with docetaxel treatment as second-line chemotherapy, to extend survival in patients with metastatic NSCLC. ENSPIRIT passed a rigorous final futility survival analysis in July and the trial is continuing as planned. Based on current enrollment projections, ENSPIRIT results could be available in the second half of 2016.

The Phase 3 AFFINITY trial is evaluating the ability of custirsen, in combination with cabazitaxel as second-line chemotherapy, to extend survival in men with metastatic CRPC whose disease has progressed following treatment with docetaxel. Final results from the AFFINITY trial for the intent-to-treat population are expected in the second half of 2016.

About Bladder Cancer
Worldwide, more than 429,000 cases of bladder cancer are diagnosed each year, and nearly 75,000 cases of bladder cancer will be diagnosed in the U.S. in 2015. Approximately 70 percent of patients present with superficial or non-muscle-invasive bladder cancer, with about 30 percent of patients having locally invasive or metastatic disease at the time of diagnosis. Of patients with locally invasive disease, 50 percent will relapse with metastases within two years. Limited options exist for both first- and second-line treatment of advanced bladder cancer and there continues to be a high unmet need for additional therapeutic options for this patient population.

About Apatorsen and ORCA
Apatorsen (OGX-427) is designed to inhibit production of heat shock protein 27 (Hsp27), disable cancer cells’ defenses and overcome treatment resistance. Hsp27 is an intracellular protein that protects cancer cells by helping them survive, leading to resistance and more aggressive cancer phenotypes. Both the potential single-agent activity and synergistic activity of apatorsen with cancer treatments may increase the overall benefit of existing therapies and augment the durability of treatment outcomes, which could lead to increased patient survival.

The ORCA (Ongoing Studies Evaluating Treatment Resistance in Cancer) program encompasses clinical trials of apatorsen. Phase 2 clinical trials are underway in bladder, lung and prostate cancers. For more information on apatorsen and ORCA, please visit www.OncoGenex.com or www.orcatrials.com.

On December 9, 2015 Celgene Corporation (NASDAQ:CELG) reported that multiple studies being presented at the San Antonio Breast Cancer Symposium will highlight the investigational use of ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) as neoadjuvant therapy in high-risk early breast cancer and in combination with a platinum in triple-negative breast cancer (Press release, Celgene, DEC 9, 2015, View Source [SID:1234508510]). Additionally, studies will evaluate ABRAXANE as a potential backbone of therapy with new immune-oncology agents.

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!

"The studies being presented at the San Antonio Breast Cancer Symposium this year support continued research into ABRAXANE as a taxane to combine with other agents in triple-negative breast cancer in both early and metastatic disease," said Jacqualyn A. Fouse, Ph.D., President, Hematology/Oncology for Celgene. "Our research efforts in this disease area underscore our ongoing commitment to patients who have few new therapeutic options."

Studies being presented include:

P1-14-11- New results from the neoadjuvant randomized GeparSepto study (GBG 69) of nab-paclitaxel at a dose of 125mg/m2 weekly compared to 150mg/m2 – December 9, 5 p.m. (Hall A-B).

P2-11-06 – Safety and clinical activity of atezolizumab (anti-PDL1) in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer – December 10, 7:30 a.m. (Hall A-B)

S6-07 – Comparison of 12 weeks neoadjuvant nab-paclitaxel combined with carboplatinum vs. gemcitabine in triple-negative breast cancer: WSG-ADAPT TN randomized phase II trial – December 11, 4:45 p.m. (Hall D)

To view all abstracts for studies being presented at the San Antonio Breast Cancer Symposium, visit View Source

ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension)(albumin-bound) is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.

Important Safety Information

WARNING – NEUTROPENIA

Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE
Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS

CONTRAINDICATIONS

Neutrophil Counts

ABRAXANE should not be used in patients who have baseline neutrophil counts of < 1500 cells/mm3
Hypersensitivity

Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS

Hematologic Effects

Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In a clinical study, Grade 3-4 neutropenia occurred in 34% of patients with metastatic breast cancer (MBC)

Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Day 1
Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1,500 cells/mm3
In the case of severe neutropenia ( < 500 cells/mm3 for 7 days or more) during a course of ABRAXANE therapy, reduce the dose of ABRAXANE in subsequent courses in patients with MBC

Resume treatment with every-3-week cycles of ABRAXANE after ANC recovers to a level > 1500 cells/mm3 and platelets recover to > 100,000 cells/mm3

Nervous System

Sensory neuropathy is dose- and schedule-dependent
The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification
If ≥ Grade 3 sensory neuropathy develops, withhold until resolution to Grade 1 or 2 followed by a dose reduction for all subsequent courses of ABRAXANE

Hypersensitivity

Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug

Hepatic Impairment

Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution
Patients with hepatic impairment may be at an increased risk of toxicity, particularly from myelosuppression, and should be monitored for development of profound myelosuppression
For MBC, the starting dose should be reduced for patients with moderate or severe hepatic impairment

Albumin (Human)

ABRAXANE contains albumin (human), a derivative of human blood
Use in Pregnancy: Pregnancy Category D

ABRAXANE can cause fetal harm when administered to a pregnant woman
If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus

Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE
Use in Men

Men should be advised not to father a child while receiving ABRAXANE

ADVERSE REACTIONS

Randomized Metastatic Breast Cancer (MBC) Study

The most common adverse reactions (≥20%) with single-agent use of ABRAXANE vs paclitaxel injection in the MBC study are alopecia (90%, 94%), neutropenia (all cases 80%, 82%; severe 9%, 22%), sensory neuropathy (any symptoms 71%, 56%; severe 10%, 2%), abnormal ECG (all patients 60%, 52%; patients with normal baseline 35%, 30%), fatigue/asthenia (any 47%, 39%; severe 8%, 3%), myalgia/arthralgia (any 44%, 49%; severe 8%, 4%), AST elevation (any 39%, 32%), alkaline phosphatase elevation (any 36%, 31%), anemia (any 33%, 25%; severe 1%, < 1%), nausea (any 30%, 22%; severe 3%, < 1%), diarrhea (any 27%, 15%; severe < 1%, 1%) and infections (24%, 20%), respectively

Sensory neuropathy was the cause of ABRAXANE discontinuation in 7/229 (3%) patients
Other adverse reactions of note with the use of ABRAXANE vs paclitaxel injection included vomiting (any 18%, 10%; severe 4%, 1%), fluid retention (any 10%, 8%; severe 0%, < 1%), mucositis (any 7%, 6%; severe < 1%, 0%), hepatic dysfunction (elevations in bilirubin 7%, 7%), hypersensitivity reactions (any 4%, 12%; severe 0%, 2%), thrombocytopenia (any 2%, 3%; severe < 1%, < 1%), neutropenic sepsis ( < 1%, < 1%), and injection site reactions ( < 1%, 1%), respectively. Dehydration and pyrexia were also reported

Renal dysfunction (any 11%, severe 1%) was reported in patients treated with ABRAXANE (n=229)
In all ABRAXANE-treated patients (n=366), ocular/visual disturbances were reported (any 13%; severe 1%)
Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients and included cardiac ischemia/infarction, chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension

Cases of cerebrovascular attacks (strokes) and transient ischemic attacks have been reported
Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations

Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or to human albumin has not been studied
There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs
There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration

DRUG INTERACTIONS

Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4

USE IN SPECIFIC POPULATIONS

Nursing Mothers

It is not known whether paclitaxel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother
Pediatric

The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated
Geriatric

A higher incidence of epistaxis, diarrhea, dehydration, fatigue, and peripheral edema was found in patients 65 years or older who received ABRAXANE for MBC in a pooled analysis of clinical studies
Renal Impairment

There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance < 30 mL/min)

DOSAGE AND ADMINISTRATION

Do not administer ABRAXANE to any patient with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN
Reduce starting dose in MBC patients with moderate to severe hepatic impairment
Dose reductions or discontinuation may be needed based on severe hematologic or neurologic toxicity
Monitor patients closely

Please see full Prescribing Information, including Boxed WARNING.

On December 09, 2015 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported that it will present a poster on Advaxis’s Lm Technology cancer immunotherapy ADXS-HER2 at the 2015 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas during Poster Session 1 on Wednesday, December 9, 2015, from 5-7 p.m. CST (Press release, Advaxis, DEC 9, 2015, View Source [SID:1234508514]).

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!

"Standard treatments for metastatic HER2-positive breast cancer are effective, but resistance develops and different approaches are needed," said Antoinette R. Tan, M.D., M.H.Sc., Chief of Breast Medical Oncology at Levine Cancer Institute, Carolinas HealthCare System, Charlotte, N.C. "This Phase 1b trial tests the approach of using an attenuated bacteria that has been shown in preclinical studies to disable the tumor’s ability to hide from and resist therapy, potentially offering a novel therapeutic strategy for patients with HER2-positive tumors."

The poster, titled "A multicenter, Phase 1b, first-in-human dose-escalation study of ADXS31-164, a listeria monocytogenes-LLO immunotherapy, in patients with HER2-expressing solid tumors," will be presented by Dr. Tan. As of October 20, 2015, this study has enrolled three patients.

The Phase 1b study in humans builds upon efficacy and safety data from Phase 1 clinical studies of ADXS-HER2 conducted in dogs with osteosarcoma, which may have important translational relevance for human patients with osteosarcoma and other HER2 expressing cancers. Preliminary data from a Phase 1 clinical trial in companion dogs with spontaneous osteosarcoma showed that administration of ADXS-HER2 following amputation and chemotherapy was safe and induced immune responses against HER2 expressing tumors in 15 out of 18 dogs. Median survival times for ADXS-HER2 treated dogs and a matched historical control group were 956 days and 423 days respectively. Overall survival rates at 1 and 2 years for dogs treated with ADXS-HER2 were 77.8 percent and 67 percent respectively and 55 percent and 28 percent respectively for the historical control group. Based on these encouraging results, ADXS-HER2 is being considered for expedited approval in 2016 by the U.S. Department of Agriculture (USDA) to treat canine osteosarcoma.

Furthermore, preliminary data from a second ongoing canine Phase 1/2 trial suggests that ADXS-HER2 in combination with palliative radiation may delay primary and metastatic tumor progression and prolong overall survival in a subset of pet dogs with spontaneous osteosarcoma that do not undergo amputation or chemotherapy.

The European Medicines Agency (EMA) recently granted Orphan Drug Designation for ADXS-HER2 for the treatment of osteosarcoma in humans.

About HER2 Expressing Solid Tumor Cancers

Human epidermal growth factor receptor 2 (HER2) is overexpressed in a percentage of solid tumors such as breast, gastric, bladder, brain, pancreatic, ovarian and pediatric bone cancer (osteosarcoma). The American Cancer Society estimates that in 2015 in the United States alone there will be 231,840 new cases of invasive breast cancer; 24,590 new cases of gastric cancer; 74,000 new cases of bladder cancer; 22,850 new cases of brain/spinal cancer; 48,960 new cases of pancreatic cancer; 21,290 new cases of ovarian cancer; and 207 new cases of pediatric osteosarcoma. HER2 expression is associated with more aggressive disease, increased risk of relapse and decreased overall survival, and is an important target for immunotherapy.

About ADXS-HER2

ADXS-HER2 is an Lm Technology immunotherapy product candidate being developed by Advaxis to target HER2 expressing cancers. ADXS-HER2 has received orphan drug designation by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of osteosarcoma. Advaxis is developing ADXS-HER2 for both human and animal health, and has seen encouraging data in canine osteosarcoma, which is considered a model for human osteosarcoma. Advaxis has licensed ADXS-HER2 and three other immunotherapy constructs to Aratana Therapeutics, Inc. for the development of pet therapeutics.

Clinical trials of ADXS-HER2 have been placed on clinical hold by the FDA. Advaxis is working closely with the FDA and expects this clinical hold will be resolved expeditiously.

On December 9, 2015 Delcath Systems, Inc. (NASDAQ: DCTH), a specialty pharmaceutical and medical device company focused on oncology with an emphasis on the treatment of primary and metastatic liver cancers, reported that the results from its Phase 3 clinical study of the Delcath Hepatic Delivery System (Melphalan/HDS) for the treatment of melanoma patients with liver metastases, have been published in the December issue of the prestigious, peer-reviewed journal, Annals of Surgical Oncology (Press release, Delcath Systems, DEC 9, 2015, View Source;p=RssLanding&cat=news&id=2121277 [SID:1234508515]). The study completed enrollment in 2009 and used an earlier version of the Melphalan/HDS and procedure. Melphalan/HDS is investigational in the United States.

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!

The study, "Results of a Randomized Controlled Multi-Center Phase III Trial of Percutaneous Hepatic Perfusion (PHP) Compared to Best Available Care for patients with Melanoma Liver Metastases," by lead investigator and senior author James F. Pingpank, Jr., M.D., Associate Professor of Surgery at the University of Pittsburgh Medical Center, and first author Marybeth S. Hughes, M.D., Center for Cancer Research, National Cancer Institute, et al., compared patients randomly assigned to receive PHP treatments with melphalan using the Melphalan/HDS, or best alternative care (BAC). Patients assigned to the PHP arm were eligible to receive up to six cycles of treatment at approximately four to eight week intervals. Patients randomized to the BAC arm were permitted to cross-over into the PHP arm at radiographic documentation of hepatic disease progression; a majority of the patients in the BAC arm did, in fact, cross over to the PHP arm. Patients who received PHP were given stem cell support in the form of platelet and red blood cell infusions to mitigate toxic side effects of melphalan. The study’s primary endpoint was hepatic progression-free survival (hPFS); secondary endpoints included overall progression free survival (oPFS), overall survival (OS), hepatic objective response rate (hOR), and safety.

In the 93 patient study, results showed that patients in the PHP arm had a statistically significant longer median hPFS of 7.0 months compared to 1.6 months in the BAC control group, according to independent imaging review. Median oPFS was 5.4 months vs. 1.6 months for BAC, according to investigator assessment. Median OS for PHP was 10.6 months vs. 10 months for BAC; sub-group analysis revealed that OS among BAC patients who had crossed over to receive PHP was 13.1 months. The hOR was 36.4% for PHP vs. 2% for BAC. With the inclusion of patients with stable disease, overall hepatic disease control rates were 75% for PHP vs. 42.9% for BAC.

The most common post-procedure adverse events (AEs) were related to grade 3 and 4 bone marrow suppression, and included neutropenia (85.7%), thrombocytopenia (80%) and anemia (62.9%). Investigators attributed three deaths to treatment with PHP. An additional death resulting from a gastric perforation occurred in a patient that crossed-over to the PHP arm.

Investigators concluded that the study "demonstrated improved control of liver disease" in patients treated with Melphalan/HDS, and that the "benefit extended to oPFS", suggesting a clear clinical benefit to disease control in the liver in the patient population. Investigators noted that the earlier version of the Melphalan/HDS and PHP procedure utilized in the study was associated with significant morbidity, and recommended modifications such as the use of prophylactic bone marrow growth factors that are already required in the clinical studies that comprise Delcath’s current Clinical Development Program in the treatment of primary and metastatic liver cancers.

"Publication of the results of our prior Phase 3 trial in such a prestigious journal is a key milestone for Delcath, and underscores the importance of these data in this area of unmet medical need. In addition, it provides us with an important tool that will enhance our efforts to expand reimbursement in certain European countries," said Jennifer K. Simpson, Ph.D., MSN, CRNP, President and Chief Executive Officer of Delcath. "Since enrollment in this study was concluded in 2009, the number of treatments administered with the enhanced Melphalan/HDS product and procedure utilized commercially in Europe have exceeded the number treated during the trial. The more recent data from European experience presented at several medical congresses this fall provide us with confidence that an improved safety profile can be demonstrated in the new, pivotal global trial we expect to launch in the coming weeks."