On June 25, 2018 Stemline Therapeutics, Inc. (Nasdaq:STML), a clinical-stage biopharmaceutical company developing novel oncology therapeutics, reported that it has completed submission of a rolling Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for ELZONRISTM (tagraxofusp; SL-401), a potential treatment for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), a CD123+ malignancy of unmet medical need for which the agent was awarded Breakthrough Therapy Designation (BTD) (Press release, Stemline Therapeutics, JUN 25, 2018, View Source [SID1234532234]).

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Survival probability in first-line BPDCN patients who received ELZONRIS (12mcg/kg/day) in Stages 1, 2 and 3

Ivan Bergstein, M.D., Stemline’s CEO, commented, "The completion of our rolling BLA submission is a major milestone for Stemline and the overall BPDCN patient community. We want to recognize the hard work of our dedicated investigators as well as the entire Stemline team in completing this submission. We also want to especially thank all of the patients and their families who participated in the clinical development program. We are committed to bringing this promising agent to BPDCN patients as rapidly as possible."

BPDCN Efficacy – Stages 1, 2, and 3, ELZONRIS (12mcg/kg/day) (n=42)
The trial of investigational agent, ELZONRIS, in patients with BPDCN was comprised of 3 stages, with Stage 3 serving as the pivotal cohort for confirmation of efficacy. To ensure ongoing access to ELZONRIS, patients with BPDCN are being enrolled in an additional cohort, Stage 4. Stage 3 met its primary endpoint with a CR+CRc (complete response + clinical complete response) rate of 54% (95% CI: 25.1, 80.8). A summary of efficacy results is shown below.

Summary table: Efficacy of ELZONRIS (12mcg/kg/day) in patients with BPDCN (Stages 1, 2 and 3 [n=42])

Line of Therapy First-line Relapsed / Refractory
n 29 13
ORR, n (%) 26 (90%) 9 (69%)
CR+CRc+CRi, n (%) 21 (72%) 5 (38%)
CR 12 1
CRc 7 3
CRi 2 1
PR, n (%) 5 (17%) 4 (31%)
Bridged to SCT, n (%) 13 (45%) 1 (8%)
Abbreviations: ORR=overall response rate; CR=complete response; CRc=clinical CR (CR with minimal residual skin abnormality); CRi=CR with incomplete hematologic recovery; PR=partial response; SCT=stem cell transplant.

Overall Safety
148 patients received ELZONRIS (12mcg/kg/day) across all Stemline-sponsored trials, including in BPDCN, myeloproliferative neoplasms, and acute myeloid leukemia. A summary of safety results is shown below.

Summary table: Safety and tolerability of ELZONRIS (12mcg/kg/day) in all Stemline-sponsored clinical trials (n=148)

Most Common Adverse Events (AEs) (>15% treatment-related AEs, TRAEs)
Preferred Term All Grades, n (%) TRAEs, n (%)
TRAEs All AEs Gr 1-2 Gr 3 Gr 4 Gr 5
ALT increased 65 (43.9%) 80 (54.1%) 31 (20.9%) 34 (23.0%) 0 (0.0%) 0 (0.0%)
AST increased 65 (43.9%) 74 (50.0%) 30 (20.3%) 31 (20.9%) 4 (2.7%) 0 (0.0%)
Hypoalbuminaemia 65 (43.9%) 73 (49.3%) 64 (43.2%) 1 (0.7%) 0 (0.0%) 0 (0.0%)
Thrombocytopenia 39 (26.4%) 48 (32.4%) 7 (4.7%) 8 (5.4%) 24 (16.2%) 0 (0.0%)
Nausea 38 (25.7%) 70 (47.3%) 37 (25.0%) 1 (0.7%) 0 (0.0%) 0 (0.0%)
Pyrexia 33 (22.3%) 60 (40.5%) 33 (22.3%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Fatigue 30 (20.3%) 67 (45.3%) 26 (17.6%) 4 (2.7%) 0 (0.0%) 0 (0.0%)
Weight increased 28 (18.9%) 42 (28.4%) 28 (18.9%) 0 (0.0%) 0 (0.0%) 0 (0.0%)
Chills 26 (17.6%) 40 (27.0%) 25 (16.9%) 1 (0.7%) 0 (0.0%) 0 (0.0%)
Capillary leak syndrome (CLS)a 25 (16.9%) 25 (16.9%) 16 (10.8%) 5 (3.4%) 3 (2.0%) 1 (0.7%)
Hypotension 23 (15.5%) 36 (24.3%) 17 (11.5%) 5 (3.4%) 1 (0.7%) 0 (0.0%)
Oedema peripheral 22 (14.9%) 57 (38.5%) 21 (14.2%) 1 (0.7%) 0 (0.0%) 0 (0.0%)
a0.7% (1/148) for all trials (12mcg/kg/day) and 1.6% (3/182) for all trials (all doses) were grade 5. A myocardial infarction, grade 5, was also reported in a patient who experienced a grade 4 CLS.

Overall Survival (OS)
In first-line BPDCN patients who received ELZONRIS (12mcg/kg/day) in Stages 1, 2 and 3, the median OS has not been reached. Median follow up was 13.8 months (range: 0.2-37.4+ months).

About ELZONRISTM (tagraxofusp; SL-401)
ELZONRISTM (tagraxofusp; SL-401) is a novel targeted investigational therapy directed to CD123, a cell surface receptor expressed on a range of malignancies. ELZONRIS has successfully completed a pivotal trial in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an indication for which it was granted Breakthrough Therapy Designation (BTD). A rolling Biologics License Application (BLA) submission has been completed. ELZONRIS is also being evaluated in clinical trials in additional indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), acute myeloid leukemia (AML), and myeloma.

On June 25, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, and Calibr, a nonprofit drug discovery division of Scripps Research, reported a collaboration to develop T-cell therapies aimed primarily at cancer, including solid tumors (Press release, AbbVie, JUN 25, 2018, View Source [SID1234527457]).

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This collaboration broadens AbbVie’s oncology research to access advanced precision medicine technology to expand the development of potentially life-changing treatments for patients with cancer.

Chimeric Antigen Receptor T-cell (CAR-T) therapies harness the power of a cancer patient’s own immune system to attack and destroy cancer cells. Despite promising results in hematological malignancies, current CAR-T therapies in development for solid tumors have demonstrated limitations due to rapid activation and expansion of CAR-T cells that can lead to serious adverse events. Calibr’s novel cell therapy program, led by Travis Young, Ph.D., director of protein sciences at Calibr, is designed to enhance safety, versatility and efficacy through a proprietary modular "switchable" CAR-T cell that uses antibody-based switch molecules to control the activation and antigen specificity of CAR-T cells.1 Calibr’s proprietary technology may enable the development of universal CAR-T-based treatments across several types of hematological and solid tumor indications.

"Calibr has assembled a premier scientific team and developed an innovative cell therapy technology that can take us to the next frontier of cancer treatment," says Mohit Trikha, Ph.D., vice president and head of Oncology Early Development at AbbVie. "The combination of AbbVie’s oncology discovery and early development expertise and Calibr’s novel switchable CAR-T therapy platform aims to advance the current standard of care, with the potential rapidly advancing new treatment options for patients."

"We’re delighted to work together with a strong partner like AbbVie to expand the impact of the CAR-T cell field to a broader range of cancers," says Peter Schultz, Ph.D., chief executive officer of Calibr and Scripps Research.

Under the terms of the license agreement, AbbVie will pay Calibr an upfront license fee and gain exclusive access to Calibr’s switchable CAR-T platform for a term of up to four years. The two organizations will work together to develop T-cell therapies directed to solid tumor targets identified by AbbVie. AbbVie also has the option to develop additional cell therapies toward AbbVie-nominated targets and license existing Calibr cell therapy programs under development for hematological and solid cancers, including Calibr’s lead program. Calibr plans to enter this lead candidate into clinical studies for lymphoma in 2019. In addition, the agreement provides AbbVie with an option to acquire an exclusive license to Calibr’s switchable CAR-T platform and programs within the first four years of the collaboration. The companies will share responsibility for preclinical development, with AbbVie responsible for clinical development and commercialization, and Calibr eligible to receive success-based milestone payments and royalties. The transaction is subject to clearance under the Hart-Scott-Rodino Antitrust Improvements Act.

On June 25, 2018 Pfizer reported overall survival (OS) results from the Phase 3 PALOMA-3 trial, which evaluated IBRANCE (palbociclib) in combination with fulvestrant compared to placebo plus fulvestrant in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer whose disease has progressed after prior endocrine therapy (Press release, Pfizer, JUN 25, 2018, View Source [SID1234527458]). The results demonstrated a positive trend in the hazard ratio favoring the IBRANCE combination, although this trend did not reach statistical significance. Overall survival is a secondary endpoint of the PALOMA-3 trial and, as such, the trial design was not optimized to detect a statistically significant difference in OS.

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"While the difference in overall survival narrowly missed the threshold for statistical significance – a high bar for any trial in this patient population – it is similar, in absolute terms, to the improvement in median progression-free survival previously demonstrated in this trial.1 We are encouraged by these results, which build on the compelling clinical benefit delivered by IBRANCE," said Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. "IBRANCE in combination with endocrine therapy has transformed the treatment landscape for patients with HR+, HER2- metastatic breast cancer."

PALOMA-3 met its primary endpoint of progression-free survival (PFS) at interim analysis and results were published in The New England Journal of Medicine in June 2015; updated PFS data were later presented at the 2016 San Antonio Breast Cancer Symposium. The trial demonstrated a statistically significant and clinically meaningful improvement in PFS for IBRANCE plus fulvestrant compared to placebo plus fulvestrant. PFS is a well-established measure of clinical benefit in metastatic breast cancer trials.2 IBRANCE in combination with fulvestrant has been approved in more than 80 countries around the world based on the PFS demonstrated in PALOMA-3.

"The duration of the survival in hormone receptor-positive metastatic breast cancer patients, and the potential for subsequent therapies to confound overall survival outcomes, make demonstrating statistically significant improvement in overall survival extremely difficult," said Nicholas Turner, M.D., Ph.D., professor of molecular oncology at The Institute of Cancer Research, London, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, as well as principal investigator of the PALOMA-3 trial. "The results from this overall survival analysis support the strong progression-free survival results from PALOMA-3 and, while not statistically significant, are encouraging for physicians and patients. We look forward to presenting the detailed data at an upcoming medical meeting."

The most common adverse reactions in PALOMA-3 included neutropenia, leukopenia, infections, fatigue and nausea; no new safety signals were identified as part of this final OS analysis.

IBRANCE in combination with endocrine therapy is a standard of care for HR+, HER2- metastatic breast cancer. IBRANCE has been prescribed to more than 120,000 patients globally to date.

The full prescribing information for IBRANCE can be found at www.pfizer.com.

About IBRANCE (palbociclib) 125 mg capsules

IBRANCE is an oral inhibitor of CDKs 4 and 6,3 which are key regulators of the cell cycle that trigger cellular progression.4,5 In the U.S., IBRANCE is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women, or fulvestrant in women with disease progression following endocrine therapy.

IMPORTANT IBRANCE (palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis.

On June 25, 2018 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 company will hold a conference call on Friday, June 29th at 8:30 a.m. EDT/5:30 a.m. PDT to discuss the ROLONTIS Phase 3 ADVANCE study data being presented at Multinational Association of Supportive Care in Cancer (MASCC) 2018 annual meeting (Press release, Spectrum Pharmaceuticals, JUN 25, 2018, http://investor.sppirx.com/news-releases/news-release-details/spectrum-pharmaceuticals-host-conference-call-highlighting [SID1234527459]). The call will feature a presentation from ADVANCE study lead investigator, Lee S. Schwartzberg, M.D., FACP Professor of Medicine and Division Chief, Hematology Oncology, The University of Tennessee Health Science Center, and Executive Director, UT/West Cancer Center.

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Conference Call Details

Friday, June 29, 2018 @ 8:30 a.m. Eastern/5:30 a.m. Pacific

Domestic: (877) 837-3910, Conference ID# 6798817

International: (973) 796-5077, Conference ID# 6798817

The conference call will also be webcast live. To access the webcast and additional documents related to the call, please visit the Investor Relations page of the Spectrum Pharmaceutical website at View Source

For interested individuals unable to join the call, a webcast replay will be available online from June 29, 2018, @ 11:30 a.m. ET/8:30 a.m. PT through July 6, 2018 until 11:30 a.m. ET/8:30 a.m. PT.

Domestic Replay Dial-In #: (855) 859-2056, Conference ID# 6798817

International Replay Dial-In #: (404) 537-3406, Conference ID# 6798817

On June 24, 2018 ERYTECH Pharma (Euronext:ERYP) (Nasdaq:ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported that it will focus its development efforts for its product candidate eryaspase on the potential treatment of selected solid tumor indications (Press release, ERYtech Pharma, JUN 24, 2018, View Source;p=RssLanding&cat=news&id=2355698 [SID1234527450]). The company also announced that it plans to cease its development program for eryaspase in acute lymphoblastic leukemia (ALL), including the withdrawal of its previously submitted MAA for eryaspase for the treatment of relapsed and refractory ALL.

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In 2017, ERYTECH announced positive results from a Phase 2b clinical trial of eryaspase combined with chemotherapy in patients suffering from second-line metastatic pancreatic cancer, as well as the intended launch of a pivotal Phase 3 clinical trial in this indication. Set-up activities are on track and the Phase 3 trial is expected to begin enrollment in the third quarter of 2018. ERYTECH now confirms that it intends to sponsor a Phase 2 proof-of-concept clinical trial of eryaspase later this year in first-line pancreatic cancer, with enrollment expected to commence in the first half of 2019.

In 2018, following the positive results in second-line metastatic pancreatic cancer, ERYTECH also evaluated other potential solid tumor indications and selected metastatic triple-negative breast cancer (TNBC) as the next indication for which to pursue clinical development of eryaspase. ERYTECH is preparing for a Phase 2 proof-of-concept clinical trial in this indication, with the first patient expected to be enrolled in the fourth quarter of 2018. ERYTECH is also evaluating development options in other pancreatic cancer settings and in additional solid tumor indications with high unmet medical need.

In order to ensure adequate supply of eryaspase for its planned clinical trials, as well as the potential commercialization of eryaspase, if approved, the Company is constructing a large-scale manufacturing facility in the United States (Princeton, New Jersey) and is also expanding its manufacturing capacity in Lyon, France. ERYTECH expects both facilities to be operational for clinical production at the expanded capacity in the first quarter of 2019.

Despite having observed favorable efficacy results and safety profile in multiple clinical trials of eryaspase in patients with ALL, ERYTECH now believes, based on recent feedback from the regulatory agencies in Europe and the United States, that significant additional investment would be required in order to seek regulatory approval of eryaspase for the treatment of ALL. In the context of the rapidly changing and increasingly competitive landscape with newly-approved treatment options for ALL, the regulatory requirements and what ERYTECH observes to be a limited market opportunity for eryaspase in ALL, ERYTECH has elected to cease further clinical development efforts in ALL and to withdraw its European MAA. The resources that will become available as a result of this strategic decision will be allocated to what ERYTECH estimates is a significantly larger unmet medical needs and market opportunity for the potential treatment of solid tumors.

ERYTECH’s preclinical development efforts are not affected by this strategic decision. The next product candidate, erymethionase, methionine-g-lyase encapsulated in red blood cells, and the ERYMMUNE (immuno-therapy) research program are also targeting solid tumor indications. ERYTECH intends to initiate a Phase 1 clinical trial of erymethionase later this year, with enrollment expected to commence in the first half of 2019.

Conference Call Details

ERYTECH management will hold a conference call on Monday, June 25, 2018 at 02:30pm CET / 08:30am EDT. Gil Beyen, Chairman and CEO, Eric Soyer, CFO and COO and Iman El-Hariry, CMO will be available for a Q&A session.