On December 5, 2016 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid cancer drugs, reported that a review of BP1001 data as a treatment for chronic myelogenous leukemia (CML) was presented in a poster at the 58th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place from December 3-6, 2016 in San Diego, CA (Filing, 8-K, Bio-Path Holdings, DEC 6, 2016, View Source [SID1234516978]).

Ana Tari Ashizawa, Ph.D., Bio-Path’s director of research, presented the poster titled "BP1001, a Novel Therapeutic for Chronic Myelogenous Leukemia." The results demonstrated that BP1001 decreased the proliferation of Gleevec (imatinib)-resistant CML cells in a dose-dependent manner. In addition, BP1001 pretreatment enhanced the inhibitory effects of Sprycel (dasatinib) in CML cells, leading to cell death. Five CML blast phase patients were enrolled in the first cohort (5 mg/m2 BP1001) of the Phase 1 BP1001 clinical study. Two CML patients, who had T315I mutation, showed significant reductions in circulating blasts during treatment. One patient’s blasts were reduced from 89% to 12%, while another patient’s blasts were reduced from 24% to 7%.

"These patient data, supported by previous in vivo and in vitro results, suggest that BP1001 has the potential to treat the 33% of CML patients who are resistant to Gleevec, the current standard of care. Sprycel is a second-generation tyrosine kinase inhibitor that is often used for Gleevec resistant patients. We are pleased that our preclinical results showed that BP1001 can enhance Sprycel activity in CML cells. These positive data give us confidence that BP1001 could play a valuable role in treating this patient population and encourage us to move forward with the initiation of our safety segment of the Phase 2 trial in patients with CML," said Peter Nielsen, chief executive officer of Bio-Path Holdings.

About BP1001

BP1001 (Liposomal Grb2 antisense) is Bio-Path’s lead product candidate, a neutral-charge, liposome-incorporated antisense drug designed to inhibit protein synthesis of Grb2 (growth factor receptor bound protein 2). Grb2 plays an essential role in cancer cell activation via the RAS pathway. Grb2 is an adapter protein that bridges signals between activated and mutated tyrosine kinases, such as Flt3, c-Kit, and Bcr-Abl, and the Ras pathway, leading to activation of the ERK and AKT proteins. Inhibition of Grb2 by BP1001 represents a significant advance in treating cancers with activated tyrosine kinases using a target not druggable with antibodies or kinase inhibitors. Inhibition of Grb2 has been demonstrated to halt cell proliferation and enhance cell killing by chemotherapeutic agents without added toxicity.

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On December 6, 2016 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology reported the presentation of data from a case match control analysis of the PROPEL Study in a poster presentation session at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Spectrum Pharmaceuticals, DEC 6, 2016, View Source [SID1234516962]).

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Abstract #4149: Case Match Control Analysis of Propel Reveals Survival Advantage for Patients with Relapsed/Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL) Treated with Pralatrexate

In this retrospective, observational study, 80 patients out of 109 treated on the PROPEL study were successfully matched 1:1 with the control population. A highly significant difference in the Overall Survival between the control population and the pralatrexate group was observed. The overall survival observed in the control population was 4.04 months (95% CI 2.60, 6.01) which was consistent with historical controls, while the median OS in for pralatrexate treated cohort was 14.78 months (95% CI 10.61-22.31). The most common adverse reactions from the PROPEL study were mucositis (70%), thrombocytopenia (41%), nausea (40%), and fatigue (36%). The most common serious adverse events were pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia. See below for Important Safety Information.

"In this case match controlled study, the overall survival observed in the pralatrexate group was over three-fold higher than a case matched control group," said Owen A. O’Connor, MD, PhD, Director of the Center for Lymphoid Malignancies, Professor of Medicine and Experimental Therapeutics at Columbia Medical Center, New York Presbyterian Medical Center. "The PROPEL study, which was a Phase 2, open-label, single-arm, multi-center, international trial, included patients that were heavily pretreated, with a median of three prior systemic therapies (ranging between 1 and 12). This is one of the first times a case match control analysis has been used to understand the impact of a drug on the outcome of a rare disease, like PTCL. Importantly, we believe this may be a valuable paradigm that can be used in other orphan diseases in cancer medicine."

"We are honored to present this important data at the 58th ASH (Free ASH Whitepaper) Meeting," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "We are encouraged to see positive data continuing to emerge from the PROPEL study that was the basis for FOLOTYN’s approval. FOLOTYN was the first drug approved for the treatment of relapsed or refractory PTCL and continues to have the leading market share in 2nd line therapy. PTCL is an aggressive disease with a poor prognosis and we are excited that FOLOTYN has the potential to improve outcome for PTCL patients. We are also looking forward to emerging new data in combination treatments that might prove to benefit PTCL patients in earlier lines of treatment and with the possibility to include FOLOTYN in future PTCL first line regimens."

About Spectrum Pharmaceuticals, Inc.

Spectrum Pharmaceuticals is a leading biotechnology company focused on acquiring, developing, and commercializing drug products, with a primary focus in Hematology and Oncology. Spectrum currently markets six hematology/oncology drugs, and has an advanced stage pipeline that has the potential to transform the Company. Spectrum’s strong track record for in-licensing and acquiring differentiated drugs, and expertise in clinical development have generated a robust, diversified, and growing pipeline of product candidates in advanced-stage Phase 2 and Phase 3 studies. More information on Spectrum is available at www.sppirx.com.

About FOLOTYN

FOLOTYN, (pralatrexate injection), a folate analogue metabolic inhibitor, was discovered by Memorial Sloan-Kettering Cancer Center, SRI International and Southern Research Institute and developed by Allos Therapeutics. In September 2009, the U.S. Food and Drug Administration (FDA) granted accelerated approval for FOLOTYN for use as a single agent for the treatment of patients with relapsed or refractory PTCL. This indication is based on overall response rate. Clinical benefit such as improvement in progression-free survival or overall survival has not been demonstrated. FOLOTYN has been available to patients in the U.S. since October 2009. An updated analysis of data from PROPEL, the pivotal study of FOLOTYN in patients with relapsed or refractory PTCL, was published in the March 20, 2011 issue of the Journal of Clinical Oncology. FOLOTYN has patent protection through July 2022, based on a five-year patent term extension through the Hatch-Waxman Act.

Important FOLOTYN Safety Information

Warnings and Precautions

FOLOTYN may suppress bone marrow function, manifested by thrombocytopenia, neutropenia, and anemia. Monitor blood counts and omit or modify dose for hematologic toxicities.

Mucositis may occur. If greater-than or equal to Grade 2 mucositis is observed, omit or modify dose. Patients should be instructed to take folic acid and receive vitamin B12 to potentially reduce treatment-related hematological toxicity and mucositis.

Fatal dermatologic reactions may occur. Dermatologic reactions may be progressive and increase in severity with further treatment. Patients with dermatologic reactions should be monitored closely, and if severe, FOLOTYN should be withheld or discontinued. Tumor lysis syndrome may occur. Monitor patients and treat if needed.

FOLOTYN can cause fetal harm. Women should avoid becoming pregnant while being treated with FOLOTYN and pregnant women should be informed of the potential harm to the fetus.

Use caution and monitor patients when administering FOLOTYN to patients with moderate to severe renal function impairment.

Elevated liver function test abnormalities may occur and require monitoring. If liver function test abnormalities are greater-than or equal to Grade 3, omit or modify dose.

Adverse Reactions

The most common adverse reactions were mucositis (70%), thrombocytopenia (41%), nausea (40%), and fatigue (36%). The most common serious adverse events are pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia.

Use in Specific Patient Population

Nursing mothers should be advised to discontinue nursing or the drug, taking into consideration the importance of the drug to the mother.

Drug Interactions

Co-administration of drugs subject to renal clearance (e.g., probenecid, NSAIDs, and trimethoprim/sulfamethoxazole) may result in delayed renal clearance.

Please see FOLOTYN Full Prescribing Information at www.FOLOTYN.com.

On December 6, 2016 Cellectar Biosciences, Inc. (Nasdaq: CLRB) (the "company"), an oncology-focused, clinical stage biotechnology company, reported that it presented a poster at the 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, which provides highlights of the company’s ongoing Phase I dose escalation clinical study of CLR 131 to assess safety and tolerability of the compound in patients with relapsed or refractory multiple myeloma (Filing, 8-K, Cellectar Biosciences, DEC 6, 2016, View Source [SID1234516979]). The poster provided detailed data related to the first two study cohorts.

The poster followed patients from initial infusion of CLR 131, the company’s lead PDC radiotherapeutic, through November 1, 2016. Results demonstrated all eight evaluable patients (of the total of ten enrolled) achieving a minimum of stable disease. The poster also reported a mean of approximately three months of progression-free survival (PFS) in Cohort 1 and four months in Cohort 2. To date, one patient in Cohort 2 continues to experience PFS. Significantly, four of eight patients experienced a greater than 50 percent reduction in serum free light chains (FLC), which are a key efficacy indicator for multiple myeloma. Per the International Myeloma Working Group (IMWG) criteria, in the absence of M protein, an FLC reduction of 50 percent or greater, is defined as a partial response. Overall, Cohort 2 patients experienced a more significant FLC reduction and a more sustained FLC response versus Cohort 1, with the difference in reduction being maintained across the entire study, and increasing at the subsequent evaluation time points. Cohort 2 patients achieved a 20 percent greater reduction in FLC on day 22 than was experienced by patients in Cohort 1, a 38 percent greater reduction at Day 43 and 43 percent greater FLC reduction at the final evaluation time point, Day 64.

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Importantly, seven of eight evaluable patients achieved a reduction in either serum or urine M protein, which also are key efficacy indicators for multiple myeloma. Similar to the FLC marker, the Cohort 2 reduction of M protein was more sustained with the patients experiencing continued reduction in M protein beyond day 64. It is also important to note that based upon M protein reduction 38 percent of patients experienced a minimal response at these low, one-time doses.

The primary endpoint for this study is to determine the safety and tolerability of CLR 131 in a heavily pre-treated patient population. Evaluable study patients received an average of four prior lines of treatment. The adverse event profile in both cohorts was similar and showed no dose dependency. While the leading adverse events were leukopenia and thrombocytopenia (30 percent each) with a median grade of 2 (mild to moderate) for both, there have been no dose-limiting toxicity events to date. Importantly, no patients experienced non-hematologic adverse events as seen with many other compounds used to treat this patient population. Specifically, there were no reports of peripheral neuropathy, fatigue, cardiovascular events, or venous thromboembolisms. The efficacy and safety profile of CLR 131 shown to date allows future development of the compound, either at the Cohort 2 dose of 18.75 mCi/m2 or at one of the future higher doses being tested. The study is currently completing Cohort 3 at a single 25 mCi/m2 dose.

"ASH is a prestigious conference and this presentation represents a peer reviewed opportunity to report encouraging efficacy and safety data from our Phase I study of CLR 131 in relapsed/refractory multiple myeloma," said Jim Caruso, president and CEO of Cellectar Biosciences. "We look forward to reporting data from Cohort 3 at a single 25 mCi/m2 dose and the initiation of our NCI-sponsored Phase II trial in multiple myeloma and other hematologic malignancies."

The Phase I multi-center, open label, dose escalation study described in the poster outlines that CLR 131 was administered as a single dose, 30-minute intravenous infusion on Day 1 with a 40 mg oral dexamethasone dose weekly for 12 weeks. Each cohort consisted of five patients, of which four were evaluable (three men, one woman in Cohort 1 and two men, two women in Cohort 2). Patients in both cohorts received an average of 4 prior treatments. Half of all patients received a stem cell transplant. All patients received proteasome inhibitors and immunomodulatory drugs prior to enrollment as well as triple combination therapy at least once.

About CLR 131
CLR 131 is an investigational compound under development for a range of hematologic malignancies. It is currently being evaluated in a Phase I clinical trial in patients with relapsed or refractory multiple myeloma. The company plans to initiate a Phase II clinical study to assess efficacy in a range of B-cell malignancies in the first quarter of 2017. Based upon pre-clinical and interim Phase I study data, treatment with CLR 131 provides a novel approach to treating hematological diseases and may provide patients with therapeutic benefits, including overall response rate (ORR), an improvement in progression-free survival (PFS) and overall quality of life. CLR 131 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a cytotoxic radioisotope, iodine-131 directly to tumor cells. The FDA has granted Cellectar an orphan drug designation for CLR 131 in the treatment of multiple myeloma.

About Phospholipid Drug Conjugates (PDCs)
Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in over 70 different xenograft models of cancer.

About Relapsed or Refractory Multiple Myeloma
Multiple myeloma is the second most common blood or hematologic cancer with approximately 30,000 new cases in the United States every year. It affects a specific type of blood cells known as plasma cells. Plasma cells are white blood cells that produce antibodies to help fight infections. While treatable for a time, multiple myeloma is incurable and almost all patients will relapse or the cancer will become resistant/refractory to current therapies.

On December 6, 2016 Celgene Corporation (NASDAQ:CELG) reported interim results from the ABOUND clinical trial program evaluating the use of ABRAXANE (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) in patients with advanced non-small cell lung cancer (NSCLC) (Press release, Celgene, DEC 6, 2016, View Source [SID1234516944]). Interim data being presented from the ABOUND trials during the IASLC 17th World Conference on Lung Cancer (WCLC) reinforces the benefit of ABRAXANE/carboplatin doublet therapy in first-line NSCLC.

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Interim ABOUND.70+ data in 128 elderly patients (≥ 70 years old) receiving first-line treatment with ABRAXANE/carboplatin for advanced NSCLC found that 91 (73%) patients experienced grade ≥2 peripheral neuropathy (PN) or grade ≥3 myelosuppression [primary endpoint]. At the time of the analyses, the median overall survival was 14.6 months and the median progression-free survival was 6.2 months, pooled across the two treatment arms [secondary endpoints]. Patients were randomized to receive first-line treatment with ABRAXANE/carboplatin either continuous weekly or weekly every three weeks with a one-week break.i Overall, 80 percent of patients discontinued treatment and the majority did so due to adverse events (24 percent) or disease progression (34 percent). Grade ≥2 PN was reported in 34% of patients, and grade ≥3 neutropenia, anemia, and thrombocytopenia was observed in 52%, 21% and 21% of patients, respectively. i

The interim ABOUND.sqm data in 284 patients receiving first-line induction treatment with ABRAXANE/carboplatin for stage IIIB/IV squamous NSCLC showed that the safety profile was consistent with that previously reported for the squamous subset in the pivotal Phase III trial.ii,iii During the induction phase, all patients received four 21-day cycles of standard ABRAXANE/carboplatin therapy.ii Overall, 119 patients (42 percent) discontinued treatment during the induction phase. The majority of patients discontinued treatment due to disease progression (34 percent) or adverse events (24 percent). The most common grade 3/4 treatment emergent adverse events (TEAEs) were hematologic and included anemia (26 percent), neutropenia (43 percent) and thrombocytopenia (15 percent).ii

Both ABOUND trials also evaluated quality of life utilizing the Lung Cancer Symptom 3-item index Scale (LCSS), Symptom Burden Index, Lung Cancer Symptom and Pulmonary Symptom Scores and the EuroQol five dimensions, five level questionnaire (EQ-5D-5L). These interim analyses suggest that quality of life was generally maintained or improved in both patient populations.iv,v

"These early data from the ABOUND clinical trial program are very encouraging, as they are consistent with the findings related to these hard to treat non-small cell lung cancer patient subgroups seen in the pivotal ABRAXANE Phase III trial," said Michael Pehl, President, Hematology and Oncology for Celgene. "These data, coupled with the ongoing studies of ABRAXANE in combination with novel agents and immunotherapies, provide us with a deeper understanding of how to treat challenging patient populations and will help us continue to develop future treatment options."

With the rapidly evolving lung cancer treatment landscape, Celgene remains committed to continuing to explore new combinations that will benefit those living with lung cancer, including patients who may not benefit from immunotherapy and targeted therapy. ABRAXANE is being actively evaluated as a foundation therapy in these patients.

Interim results of the phase I study of the immunotherapy agent nivolumab in combination with ABRAXANE/carboplatin in 22 patients with Stage IIIB/IV NSCLC will also be presented at WCLC. Patients received four cycles of standard ABRAXANE/carboplatin therapy in combination with nivolumab, followed by nivolumab monotherapy starting at cycle 5. The primary endpoints were number of patients with dose limiting toxicity and percentage of patients with grade 3/4 TEAEs or treatment discontinuation due to a TEAE. The interim data suggests that combining ABRAXANE/carboplatin with nivolumab may have promising anti-tumor activity in patients with advanced NSCLC with no unexpected adverse events (AEs).vi

The most common grade 3/4 AEs observed during the study included neutropenia (45 percent), anemia (35 percent), hypokalemia (15 percent), and vomiting (15 percent).vi The study has been expanded and patients are currently enrolling in part 2. Additional data on the safety and efficacy of this combination in multiple tumor types will be presented at a future medical meeting.

Additional ABRAXANE Data Presented at WCLC

There will also be an oral presentation at WCLC focused on new findings from the phase III registration study for ABRAXANE (Abstract 4460), which reports on the impact of depth of response on survival in patients with advanced NSCLC treated with first-line chemotherapy. Real-world analyses of US veterans with NSCLC are also being presented at WCLC, evaluating prevalence of squamous NSCLC in veterans vs. the general population (Abstract 4737) and the prevalence of autoimmune disease in veterans with NSCLC (Abstract 4745).

Additional investigator initiated studies presented at WCLC also evaluated ABRAXANE as first-line (Posters P2.03a-028 and P2.06-018), second-line (Posters P2.03a-040, P2.03a-054 and P2.03a-056) or third-line (Poster P2.06-015) treatment for advanced NSCLC patients, as well as in the adjuvant (Poster P2.03a-070) and neoadjuvant (Poster P2.04-034) settings and in chemo-naïve patients with an EGFR mutation (Poster P3.02b-061).

ABOUT ABOUND

ABOUND is a multi-phase, open-label, multicenter clinical trial program evaluating the use of ABRAXANE in combination with carboplatin or other novel agents, including immunotherapy, as first- or second-line treatment of patients with advanced non-small cell lung cancer (NSCLC). The ABOUND trials included patients 70 years and older, as well as those with poorer performance status or squamous disease and those receiving second-line+ treatment.vii,viii,ix,x

ABOUT THE ABRAXANE/NIVOLUMAB STUDY

This is a phase I, open-label, multicenter, safety study of ABRAXANE-based chemotherapy regimens administered prior to and/or in combination with nivolumab in pancreatic cancer, NSCLC and metastatic breast cancer. This is a six arm study assessing two treatment arms per tumor-type/indication.

About ABRAXANE (nab-paclitaxel)

ABRAXANE is indicated for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy.

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 < 1500cells/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 47% of patients with non-small cell lung cancer (NSCLC)
Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15
Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1500 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 NSCLC
Resume treatment if recommended at permanently reduced doses for both weekly ABRAXANE and every-3-week carboplatin after ANC recovers to at least 1500 cells/mm3 and platelet count of at least 100,000 cells/mm3 on Day 1 or to an ANC of at least 500 cells/mm3 and platelet count of at least 50,000 cells/mm3 on Days 8 or 15 of the cycle
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 ABRAXANE treatment until resolution to ≤ Grade 1 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 NSCLC, 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

Non-Small Cell Lung Cancer (NSCLC) Study

The most common adverse reactions (≥20%) of ABRAXANE in combination with carboplatin are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue
The most common serious adverse reactions of ABRAXANE in combination with carboplatin for NSCLC are anemia (4%) and pneumonia (3%)
The most common adverse reactions resulting in permanent discontinuation of ABRAXANE are neutropenia (3%), thrombocytopenia (3%), and peripheral neuropathy (1%)
The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (24%), thrombocytopenia (13%), and anemia (6%)
The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (41%), thrombocytopenia (30%), and anemia (16%)
The following common (≥10% incidence) adverse reactions were observed at a similar incidence in ABRAXANE plus carboplatin-treated and paclitaxel injection plus carboplatin-treated patients: alopecia (56%), nausea (27%), fatigue (25%), decreased appetite (17%), asthenia (16%), constipation (16%), diarrhea (15%), vomiting (12%), dyspnea (12%), and rash (10%); incidence rates are for the ABRAXANE plus carboplatin treatment group
Adverse reactions with a difference of ≥2%, Grade 3 or higher, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (28%, 7%), neutropenia (47%, 58%), thrombocytopenia (18%, 9%), and peripheral neuropathy (3%, 12%), respectively
Adverse reactions with a difference of ≥5%, Grades 1-4, with combination use of ABRAXANE and carboplatin vs combination use of paclitaxel injection and carboplatin in NSCLC are anemia (98%, 91%), thrombocytopenia (68%, 55%), peripheral neuropathy (48%, 64%), edema peripheral (10%, 4%), epistaxis (7%, 2%), arthralgia (13%, 25%), and myalgia (10%, 19%), respectively
Neutropenia (all grades) was reported in 85% of patients who received ABRAXANE and carboplatin vs 83% of patients who received paclitaxel injection and carboplatin
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 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

Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients ≥65 years of age treated with ABRAXANE and carboplatin in NSCLC
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 NSCLC 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.

Please refer to the Summary of Product Characteristics for full European prescribing information.

On December 6, 2016 Stemline Therapeutics, Inc. (Nasdaq:STML) reported the presentation of SL-401 lead-in data from its ongoing Phase 2 trial in acute myeloid leukemia (AML) in remission with minimal residual disease (MRD) and ongoing Phase 2 trial in high-risk myeloproliferative neoplasms (MPN) at the 2016 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Stemline Therapeutics, DEC 6, 2016, View Source [SID1234516963]). The AML/MRD results were delivered via oral presentation by Andrew A. Lane, M.D., Ph.D., from the Dana-Farber Cancer Institute (Boston, MA) and the MPN results were presented by Mrinal S. Patnaik, M.D. from the Mayo Clinic (Rochester, MN).

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The full presentations are available on the Stemline website, under the "Scientific Presentations" tab (see: View Source).

Safety Overview

SL-401 was found to be safe and well tolerated, and side effects were predictable and manageable. The lead-in dose escalation stages of both Phase 2 studies (3 x 3 design) were completed without dose limiting toxicity (DLT) and a maximum tolerated dose (MTD) was not reached in either study (n=9 patients in AML/MRD lead-in; n=9 patients in MPN lead-in). 12 ug/kg/day was the highest tested dose in both studies and is currently the dose level being used in the expansion stage of both studies.
Efficacy Overview

AML/MRD – Early signs of efficacy in the AML study included an MRD+ AML patient who sustained a decrease in MRD, determined locally, treated at 12 ug/kg/day who then went on to stem cell transplant. The expansion stage is currently enrolling and, for uniformity, will utilize a central facility for MRD analysis.

MPN – Early signs of efficacy in the MPN study including a patient with chronic myelomonocytic leukemia (CMML) who sustained a bone marrow complete response (BMCR) and reduction in spleen size. The expansion stage is currently enrolling CMML as well as additional MPN types including myelofibrosis, mastocytosis, and primary eosinophilic disorder.
Andrew A. Lane, M.D., Ph.D., lead author on the AML study, commented, "Given the unacceptably high relapse rates seen in AML, MRD has emerged as an important predictor of relapse with CD123 as a key target for therapy. The preliminary results seen with SL-401 in this setting are promising. We look forward to enrolling patients in the expansion stage of the trial as we continue to optimize and refine methods to assess and follow MRD."

Mrinal S. Patnaik, M.D., lead author on the MPN study, noted, "The early data from the dose escalation portion of the trial suggests SL-401 can be dosed safely in this patient population. Additionally, we are observing encouraging signs of clinical activity in several patients. We look forward to enrolling patients in the expansion stage of the trial."