On March 20, 2019 Diffusion Pharmaceuticals Inc. (Nasdaq: DFFN), a cutting-edge biotechnology company developing new treatments for life-threatening medical conditions by improving the body’s ability to bring oxygen to the areas where it is needed most, reported financial results for the year ended December 31, 2018 and provided a business update (Press release, Diffusion Pharmaceuticals, MAR 20, 2019, View Source [SID1234534500]).

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2018 was marked by significant developments related to the Company’s lead drug candidate, trans sodium crocetinate (TSC), for the treatment of stroke and cancer. During the third quarter Diffusion received approval from the U.S. Food and Drug Administration (FDA) to enroll patients in an ambulance-based Phase 2 clinical trial testing TSC for the treatment of acute stroke, while the in-ambulance trial design was presented at several important medical conferences. The trial, named PHAST-TSC (Pre-Hospital Administration of Stroke Therapy-TSC), will involve 23 hospitals across urban, suburban and rural areas in Los Angeles County and Central Virginia, working closely with approximately 150 emergency medical transport groups. PHAST-TSC will be led by researchers at the University of California Los Angeles (UCLA) and the University of Virginia (UVA). Diffusion is working to engage local ambulance companies and expects the first patients to be treated in the coming months. Results for the trial will potentially be available in just under two years, subject to Diffusion receiving the necessary funding.

The Company continues to screen and enroll patients in its Phase 3 INTACT (INvestigation of TSC Against Cancerous Tumors) program, using TSC to treat inoperable glioblastoma multiforme (GBM) brain cancer. In Phase 2 testing TSC demonstrated a nearly four-fold improvement in overall survival at two years for the subset of inoperable GBM patients compared with the control group of GBM patients.

Commenting on 2018 and plans for 2019, David Kalergis, chairman and chief executive officer of Diffusion, said, "In the coming weeks we expect to complete enrollment in the initial dose-escalation cohort of the INTACT trial. In addition, we expect to begin enrollment in PHAST-TSC during the second quarter of 2019. We continue to be excited about the potential for TSC to bring new hope to patients with life-threatening unmet medical needs and making TSC a commercial success.

Several patents were allowed and issued during the course of 2018, strengthening the Company’s intellectual property portfolio around broad uses of TSC in hypoxic conditions such as stroke, and as a treatment for solid cancerous tumors in conjunction with radiation and chemotherapy. Of note, a U.S. patent was issued for TSC in conjunction with tissue plasminogen activator (tPA) for the treatment of stroke. tPA is the only FDA-approved therapeutic for this indication. At the end of 2018, the company had 56 issued patents in the U.S. and abroad.

2018 Financial Results

Diffusion had cash and cash equivalents of $8.0 million as of December 31, 2018. The Company believes its cash and cash equivalents are sufficient to fund operations into July 2019.

Diffusion recognized $5.8 million in research and development expenses during 2018, compared with $5.1 million during 2017. This increase was primarily attributable to a $1.7 million increase in Phase 3 GBM trial expenses and to a $0.2 million increase in salary and wages expenses, partially offset by a $1.2 million decrease in manufacturing and other costs.

General and administrative expenses were $6.2 million during 2018, which were flat compared with 2017. Salaries and wages expense increased by $0.6 million, which was offset by a $0.6 million decrease in professional fees.

The Company recognized a non-cash goodwill impairment charge of $6.9 million during the year ended December 31, 2018 as a result of a sustained decrease in our market capitalization during the second half of 2018. There was no such charge in 2017.

Net cash used in operating activities for 2018 was $10.8 million, compared with $12.3 million during 2017

On March 20, 2019 Petra Pharma Corporation ("Petra"), a leader in phosphoinositide (PI) signaling pathway inhibition, reported it has secured a global license from Takeda Pharmaceutical Company Limited ("Takeda") to develop, manufacture and commercialize serabelisib and two additional PI3Kα-specific inhibitors (Press release, Petra Pharma, MAR 20, 2019, View Source [SID1234554009]). The agreement grants Petra a license for all human therapeutic uses, except for a subset of undisclosed rare-disease indications, which Takeda had previously out-licensed.

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Petra plans to initiate a Phase 1b/2 study with serabelisib in late 2019 to advance pioneering research and insights in PI signaling pathways with a focus on PIK3CA-mutated solid tumors. The PI3K signaling pathway is a frequently mutated pathway in human cancer.

"Today marks a transformational moment for Petra and a new era in the therapeutic use of PI3K inhibitors. We are pioneering new approaches that have the potential to increase tumor responses with PI3K inhibitors and minimize side effects, with profound clinical implications for patients diagnosed with a PIK3CA-mutated tumor," said President and CEO, Brian O’Callaghan.

Petra’s leading-edge research builds on the recent work of Scientific Co-Founder, Lewis Cantley, Ph.D. (Weill Cornell Medical Center) and his collaborators, whose paper in the August 2018 issue of Nature* identified strategies to disrupt the glucose/insulin feedback loop with the potential to dramatically improve the anti-tumor response.

"Current treatment modalities have been challenging due to an on-target effect of PI3Kα inhibitors causing hyperglycemia and consequent elevation of serum insulin, which can re-activate PI3K in tumors, allowing them to survive," said Dr. Cantley. "The approach Petra is taking disrupts the glucose/insulin feedback loop, which in preclinical models significantly increases anti-tumor efficacy."

This is the first licensing agreement between Petra and Takeda. Financial terms of the agreement were not disclosed.

* Hopkins BD, Pauli C, Du X, et al. Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature. 2018;560(7719):499-503.

On March 19, 2019 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with a primary focus on myelodysplastic syndromes, reported that the Company will release its year-end 2018 financial results on Tuesday, March 26, 2019, before the market opens (Press release, Onconova, MAR 19, 2019, View Source [SID1234534456]). Management will host a conference call on Tuesday, March 26, 2019, at 9:00 a.m. Eastern Time to discuss these results and provide an update on its pipeline programs. Interested parties may access the call by dialing toll-free (855) 428-5741 from the U.S. or (210) 229-8823 internationally and using conference ID 1878978.

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The conference call will also be webcast live. Please visit www.onconova.com to access the webcast. A replay will be available for 90 days.

About Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are conditions that can occur when the blood-forming cells in the bone marrow become dysfunctional and thus produce an inadequate number of circulating blood cells. It is frequently associated with the presence of blasts or leukemic cells in the marrow. This leads to low numbers of one or more types of circulating blood cells, leading to the need for blood transfusions. In MDS, some of the cells in the bone marrow are abnormal (dysplastic) and may have genetic abnormalities associated with them. Different cell types can be affected, although the most common finding in MDS is a shortage of red blood cells (anemia). Patients with higher-risk MDS may progress to the development of acute leukemia.

On March 19, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) reported its financial results for the fourth quarter and year ended December 31, 2018 as well as provided corporate and operational updates on clinical trials, research and development, recent hires, and intellectual property (Press release, Actinium Pharmaceuticals, MAR 19, 2019, View Source [SID1234534474]).

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Company Highlights:

Presented interim Phase 3 SIERRA trial data at the 2018 ASH (Free ASH Whitepaper) and 2019 TCT Meetings. The SIERRA trial (Study of Iomab-B in Elderly Relapsed or Refractory AML) is a 150-patient pivotal Phase 3 multi-center randomized trial that will compare outcomes of patients who receive Iomab-B and a BMT or Bone Marrow Transplant to those patients receiving physician’s choice of salvage chemotherapy, defined as conventional care, as no standard of care exists for this patient population. Key highlights from the SIERRA Trial presented at ASH (Free ASH Whitepaper) and the TCT Meetings include:
All patients receiving a therapeutic dose of Iomab-B engrafted despite active disease with high blast count (median 30%, or median 45% for crossover patients)
15 of 19 (79%) patients in the control arm failed to achieve a complete response
67% (10/15) of patients eligible for crossover successfully transplanted after Iomab-B treatment
All patients receiving Iomab-B and a BMT (28/28) achieved Donor Chimerism prior to day 100
94% of patients initially randomized to receive Iomab-B and a BMT (17/18) achieved Full Donor Chimerism > 95% prior to day 100 with 1 patient achieving 65% donor chimerism
90% of patients who crossed-over to receive Iomab-B and a BMT (9/10), after salvage chemotherapy in the control arm failed to produce a CR or Complete Response, also achieved Full Donor Chimerism > 95% prior to day 100 with 1 patient achieving 86% donor chimerism
The SIERRA trial is currently enrolling patients at 18 sites in the U.S and Canada including many of the leading BMT sites based on volume. Patients with active, relapsed or refractory AML have dismal prognoses and are typically not offered potentially curative transplant as an option, largely because salvage treatments have a limited ability to produce a complete remission, which is necessary prior to conventional BMT if conventional BMT is to be successful. However, with Iomab-B targeted conditioning, a complete remission prior to starting the Iomab-B conditioning is not necessary for a successful transplant. Iomab-B is an ARC or Antibody Radiation-Conjugate that targets CD45, an antigen expressed on leukemia, lymphoma and immune cells, and delivers Iodine-131 that kills targeted cells via linear energy transfer. Key highlights from the SIERRA Trial presented at ASH (Free ASH Whitepaper) and the TCT Meetings include:

Initiated Actimab-A venetoclax combination trial. This novel Phase 1/2 trial will study Actimab-A in combination with venetoclax for patients with relapsed or refractory AML or Acute Myeloid Leukemia. Venetoclax is a BCL-2 or B-Cell Lymphoma 2 inhibitor, BCL-2 is one of several proteins encoded by the BCL2 gene family, which regulates apoptosis or programmed cell death. Venetoclax is jointly developed and marketed by AbbVie and Genentech and is approved for patients with CLL or Chronic Lymphocytic Leukemia, and SLL or Small Lymphocytic Leukemia and AML with an HMA or hypomethylating agent.
Response rates of relapsed or refractory patients with AML to venetoclax as a single agent have been reported to be 19%. In a recent webinar, Actinium highlighted that one study observed that of 21 relapsed or refractory AML patients that responded to venetoclax and an HMA, 13 (62%) stopped venetoclax treatment with disease progression being the most common reason for discontinuation. The study also observed that no patients with secondary AML responded to treatment with venetoclax and patients with FLT3 mutations had lower response rates.

MCL-1 is another protein encoded by the BCL2 gene family that is also overexpressed in cancers, including relapsed or refractory AML, that prevents apoptosis and promotes resistance to venetoclax, which does not bind to MCL-1. It has been observed that MCL-1 levels can be depleted with radiation, but only external radiation was used in these studies. Actinium is studying the use of targeted internalized radiation from Actimab-A to deplete MCL-1 levels thereby removing the AML cells’ resistance mechanism and rendering them more susceptible to venetoclax. Actimab-A is an ARC that delivers internalized radiation from the alpha-particle emitting isotope Ac-225 or Actinium-225 via the CD33 targeting monoclonal antibody lintuzumab

Actinium is conducting this combination study with the goal of offering a therapy to patients that do not respond or stop responding to venetoclax. In addition to the potential to deplete MCL-1 levels, Actimab-A’s radiation mechanism of action is agnostic to cytogenetic mutations and has shown to produce responses in patients with secondary AML. Actinium is also planning a Phase 1/2 trial that will study Actimab-A in combination with venetoclax and a hypomethylating agent. This triplet trial will also enroll patients with relapsed or refractory AML and is expected to initiate in the first half of 2019.

Advanced to second patient cohort in Actimab-A CLAG-M trial. Actinium is also studying Actimab-A in combination with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim, and mitoxantrone) in patients with relapsed or refractory AML. Chemotherapy and radiation are routinely used in combination together with a majority of patients receiving external beam radiation. However, patients with AML are not treated with external radiation as the diffuse nature of the disease prohibits therapeutic levels of radiation from being used due to safety and toxicity concerns. Ac-225 is a potent isotope capable of causing lethal double stranded breaks in cell DNA but its energy is limited to a few cell diameters. CD33 is an antigen expressed on the surface of a vast majority of AML cells. This trial is evaluating the effect targeted internalized radiation via Actimab-A will have in combination with CLAG-M on safety and tolerability, response rates, rates of BMT, PFS or progression-free survival, and OS or overall survival.
In the first dose cohort, patients received 0.25 uCi/kg of Actimab-A. This combination trial is designed as a 3+3 dose escalation study. No DLT’s or dose limiting toxicities were reported in the first patient cohort. As a result, and per the study protocol, the Institutional Review Board (IRB) at MCW authorized the initiation of the second dosing cohort, in which patients are receiving 0.50 uCi/kg of Actimab-A. Assuming no DLTs are observed in the second cohort, three patients will be treated and the study will progress to the third and final cohort that will study Actimab-A at a dose of 0.75 uCi/kg.

Advanced to second module of collaborative research program with Astellas Pharma, Inc. (Astellas). The Company’s previously announced research collaboration with Astellas is using its AWE or Antibody Warhead Enabling technology platform to conjugate and label select Astellas targeting agents with the potent Ac-225 payload. In January 2019, Actinium announced that it completed the first module of the collaboration and the second module had been initiated. Since launching its AWE Program in November 2017, Actinium has achieved the following milestones:
Appointed Dr. Dale Ludwig, a leading antibody therapeutics and antibody conjugate expert, as Chief Scientific Officer
Presented positive data at ASH (Free ASH Whitepaper) 2017 demonstrating the superior in vitro cell killing properties of Ac-225 labeled daratumumab or Darzalex, Johnson & Johnson’s blockbuster CD38 targeting therapy for multiple myeloma
Presented additional positive data from in vivo animal studies at AACR (Free AACR Whitepaper) 2018 demonstrating enhanced tumor control and survival with Ac-225 labeled daratumumab
Significantly strengthened senior leadership team in core areas. Appointed Cynthia Pussinen as Executive Vice President of Technical Operations and Supply Chain. Ms. Pussinen brings 25 years of highly relevant experience to Actinium gained at Pfizer and Ipsen Biosciences, Inc. Most recently, she was Head of Strategic Portfolio Management, Worldwide Research & Development. In this role she led efforts to maximize the value of Pfizer’s pre-Proof of Concept portfolio across 6 research units, including driving pipeline decision making, portfolio prioritization and clinical portfolio investment efforts across the R&D organization. Previously, President and General Manager of Ipsen Biosciences, Inc. where she led the operational and strategic directions of this subsidiary company, including maintaining an annual operating budget of more than $100 million, and managing two sites with more than 220 employees.
Appointed Qing Ling, PhD, DABR to newly created position of Vice President, Head of Radiation Sciences. This newly created position will drive innovation in line with Actinium’s strategic vision related to its AWE technology platform. Dr. Liang will collaborate closely with clinical trial sites and their staffs, regulators and other key stakeholders to help advance and optimize Actinium’s clinical ARC programs to deliver the best possible outcomes for patients. Dr. Liang is a Medical Physicist certified by the American Board of Radiology and prior to Actinium was Medical Physicist and Assistant Professor at Fox Chase Cancer Center at Temple University (Philadelphia, PA). Prior to that, she had worked at Mercy Health System (Janesville, WI), Turville Bay MRI & Radiation Oncology (Madison, WI), University of Wisconsin Hospital (Madison, WI), and UW Accredited Dosimetry Calibration Laboratory (Madison, WI).

Appointed Mamata Gokhale, PhD, RAC as Vice President, Global Head of Regulatory Affairs. Dr. Gokhale brings over 20 years of regulatory affairs experience to Actinium that began at the FDA as a reviewer before transitioning to industry where she worked at biotechnology and pharma companies including Amgen, Watson Pharma, Neumedicines Inc. and global Contract Research Organizations including Voisin Consulting Life Sciences and Paraxel International. At Amgen Dr. Gokhale successfully contributed to approvals and expansion of Prolia , Xgeva , Vectibix and Sensipar . Dr. Gokhale’s regulatory experience includes developing regulatory strategies for small molecules, monoclonal antibodies, cell and gene therapies, leading and managing regulatory interactions, requesting orphan drug, breakthrough therapy and fast track designations and pediatric vouchers, resolution of clinical hold issues, developing target product profiles, core data sheets and conducting labeling negotiations.

Significantly expanded patent portfolio. Through rejuvenated R&D activity Actinium’s patent portfolio has increased to a total of 111 issued and pending patents in the U.S. and internationally, which is up from the 75 reported previously. This intellectual property portfolio, contained within 28 patent families, covers key areas of Actinium’s business. The estate covers ARC generation, composition of matter, formulations, and methods of administration for solid and liquid cancers as well as radionuclide production including the manufacturing of Ac-225 or Actinium-225. Actinium’s recent patent filings pertain to its planned pivotal Actimab-MDS targeted conditioning trial, ARC combination trials of Actimab-A with venetoclax and CLAG-M, as well as its next-generation ARC’s resulting from its AWE technology platform. These follow recent patent filings from Actinium related to its Iomab-ACT next generation lymphodepletion program for CAR-T and adoptive cell therapies that includes four pending patents and one provisional patent application for cancer and non-malignant diseases. These new filings are in addition to Actinium’s broad intellectual property and patent portfolio that cover direct labeling, or conjugation and labeling of a biomolecular targeting agent to a radionuclide warhead, and its development and use as a therapeutic regimen for the treatment of diseases such as cancer. Actinium has patents on the use of the "gold standard" chelator DOTA, an organic compound used to attach, or conjugate, the radionuclide Ac-225 to monoclonal antibodies and any conceivable derivative thereof, as well key patents covering the manufacturing of Ac-225 in a cyclotron. In addition, Actinium extensive know-how and trade secrets in the application of its AWE technology platform to support its existing pipeline and potential collaborations.
Research and development expenses for the year ended December 31, 2018 declined by $0.7 million to $17.0 million compared to $17.7 million for the year ended December 31, 2017. The decrease was primarily attributable to the recognition of payments received from Astellas, with such payments accounted for as a reduction in research and development expenses, as well as lower expenses related to Actimab-A and lower non-cash stock-based compensation expense.
General and administrative expenses declined by $2.5 million to $6.7 million for the year ended December 31, 2018 compared to $9.2 million for the year ended December 31, 2017, primarily due to lower compensation expense, resulting from lower non-cash stock-based compensation expense during 2018 and one-time charges paid to certain former employees in 2017.

Actinium reported a cash and cash equivalent balance of $13.6 million as of December 31, 2018. In its Annual Report of Form 10-K which was filed with the Securities and Exchange Commission on March 15, 2018, the Company’s audited financial statements contained a going concern explanatory paragraph in the audit opinion from Marcum LLP, its independent registered public accounting firm.

Net loss decreased by $2.9 million to $23.7 million for the year ended December 31, 2018 compared to $26.6 million for the year ended December 31, 2017. The decrease was primarily due to lower general and administrative expenses and research and development expenses.

Upcoming Conferences
Actinium’s management will present at the Oppenheimer & Co. 29th Annual Healthcare Conference, being held March 19-20. The details of Actinium’s presentation are as follows:

Presentation Details:
Date: Wednesday, March 20, 2019
Time: 1:35 pm Eastern Time
Room: Consulate
Venue: Westin Grand Central Hotel in New York City

In addition, members of Actinium’s executive, clinical, R&D, commercial and CMC teams will be attending the AACR (Free AACR Whitepaper) or American Association of Cancer Research Annual Meeting being held March 29 – April 3 at the Georgia World Congress Center in Atlanta, Georgia and the TAT or 11th International Symposium on Targeted-Alpha-Therapy being held April 1 – 4 at the Fairmont Chateau Laurier in Ottawa, Canada.

On March 19, 2019 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that six abstracts highlighting progress in the Rubraca clinical development and lucitanib preclinical research programs will be presented at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place March 29 – April 3 in Atlanta (Press release, Clovis Oncology, MAR 19, 2019, View Source [SID1234534502]).

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The accepted abstracts summarize multiple clinical trials and nonclinical research in which Rubraca is being studied as single agent and combination therapy in a variety of solid tumor types including pancreatic, ovarian, bladder and prostate. In addition, one abstract summarizes ongoing nonclinical research for lucitanib.

"We are actively evaluating the potential utility of Rubraca and lucitanib in a wide range of solid tumors," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We know that many healthcare professionals and patients are hopeful about the role that these therapies may play in treating these cancers, and we are pleased to share our latest updates at this year’s AACR (Free AACR Whitepaper) meeting."

The five Clovis Oncology-sponsored presentations and one presentation of an investigator-initiated trial comprise:

Abstract CT234 – A Phase II, single arm study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic mutation in BRCA1, BRCA2 or PALB2

Presenter: Kim A. Reiss Binder
Session: CTMS03 Developmental Therapeutics: Clinical Results of Novel Agents
Date/Time: April 2, 2019, 3:35 – 3:50 PM EDT
Location: Marcus Auditorium- Bldg. A-GWCC
Abstract 727 (Poster 1) – Comprehensive genomic profiling of >1000 plasma and tumor tissue samples from metastatic castration-resistant prostate cancer (mCRPC) patients gives insight into targeted treatment strategies

Presenter: Foad Green
Session: Molecular and Cellular Biology/Genetics; Cancer Genomics 1
Date/Time: Sunday, March 31, 2019 from 1:00 – 5:00 PM EDT
Location: Exhibit Hall B, Section 33
Abstract 1214 (Poster 11) – Enhancement of anti-PD-1 antitumor efficacy in syngeneic preclinical models by the angiogenesis inhibitor lucitanib

Presenter: Rachel L. Dusek
Session: Experimental and Molecular Therapeutics; Cancer Immunotherapy
Date/Time: Monday, Apr 1, 2019 8:00 AM – 12:00 PM EDT
Location: Exhibit Hall B, Section 10
Abstract 3888 (Poster 8) – Intracranial evaluation of the in vivo pharmacokinetics, brain distribution, and efficacy of rucaparib in BRCA-mutant, triple-negative breast cancer

Presenter: Minh Nguyen
Session: Experimental and Molecular Therapeutics; Pharmacokinetics and Pharmacodynamics / Preclinical Toxicology
Date/Time: Tuesday, Apr 2, 2019 1:00 – 5:00 PM
Location: Exhibit Hall B, Section 13
Abstract CT158 (Poster 2) – ATHENA (GOG-3020/ENGOT-ov45): a randomized, double-blind, placebo-controlled, Phase III study of rucaparib + nivolumab following front-line platinum-based chemotherapy in ovarian cancer

Presenter: Shannon N. Westin
Session: Phase I-III Trials in Progress: Part 2
Date/Time: Tuesday, Apr 2, 2019 8:00 AM – 12:00 PM EDT
Location: Exhibit Hall B, Poster Section 17
Abstract CT179 (Poster 23) – ATLAS: A Phase II, open-label study of rucaparib in patients with locally advanced or metastatic urothelial carcinoma

Presenter: Petros Grivas
Session: Phase I-III Trials in Progress: Part 2
Date/Time: Tuesday Apr 2, 2019 8:00 AM – 12:00 PM EDT
Location: Exhibit Hall B, Poster Section 17
The five Clovis-sponsored posters will be available online at View Source at once they are presented at the meeting.

About Rubraca (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian, metastatic castration-resistant prostate, and bladder cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca U.S. FDA Approved Indications

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Rubraca is indicated as monotherapy for the treatment of adult patients with deleterious BRCA mutations (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur uncommonly in patients treated with Rubraca, and are potentially fatal adverse reactions. In approximately 1100 treated patients, MDS/AML occurred in 12 patients (1.1%), including those in long-term follow-up. Of these, five occurred during treatment or during the 28-day safety follow-up (0.5%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 28 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA-damaging agents. Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1).

Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose (see Dosage and Administration [2.2] in full Prescribing Information) and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample cytogenetic analysis. If MDS/AML is confirmed, discontinue Rubraca.

Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca.

Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1–4) were nausea (76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%), constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia (29%), nasopharyngitis/upper respiratory tract infection (29%), stomatitis (28%), decreased appetite (23%) and neutropenia (20%).

Most common laboratory abnormalities in ARIEL3 (≥ 25%; Grade 1–4) were increase in creatinine (98%), decrease in hemoglobin (88%), increase in cholesterol (84%), increase in alanine aminotransferase (ALT) (73%), increase in aspartate aminotransferase (AST) (61%), decrease in platelets (44%), decrease in leukocytes (44%), decrease in neutrophils (38%), increase in alkaline phosphatase (37%) and decrease in lymphocytes (29%).

Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1–4) were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea (21%) and thrombocytopenia (21%).

Most common laboratory abnormalities in Study 10 and ARIEL2 (≥ 35%; Grade 1–4) were increase in creatinine (92%), increase in alanine aminotransferase (ALT) (74%), increase in aspartate aminotransferase (AST) (73%), decrease in hemoglobin (67%), decrease in lymphocytes (45%), increase in cholesterol (40%), decrease in platelets (39%) and decrease in absolute neutrophil count (35%).

Co-administration of Rubraca can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring. Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the last dose. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Clovis Oncology, Inc. at 1-844-258-7662.

Click here or full Prescribing Information and additional Important Safety Information.

Rubraca ▼ (rucaparib) EU Authorized Use and Important Safety Information

Rucaparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rucaparib is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Summary warnings and precautions: Haematological toxicity: Patients should not start Rubraca until they have recovered from haematological toxicities caused by previous chemotherapy (≤ CTCAE Grade 1). Complete blood count testing prior to starting treatment with Rubraca and monthly thereafter is advised. Rubraca should be interrupted or dose reduced and blood counts monitored weekly until recovery for the management of low blood counts. Myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML): If MDS/AML is suspected, the patient should be referred to a haematologist for further investigation. If MDS/AML is confirmed, Rubraca should be discontinued. Photosensitivity: Patients should avoid spending time in direct sunlight as they may burn more easily. When outdoors, patients should wear protective clothing and sunscreen with SPF of 50 or greater. Gastrointestinal toxicities: Low grade (CTCAE Grade 1 or 2) nausea and vomiting may be managed with dose reduction or interruption. Additionally, antiemetics may be considered for treatment or prophylaxis.

Click here to access the current Summary of Product Characteristics. Healthcare professionals should report any suspected adverse reactions via their national reporting systems.

About Lucitanib

Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDFGRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3).

Emerging clinical data support the combination of angiogenesis inhibitors and immunotherapy to increase effectiveness in multiple cancer indications. Angiogenic factors, such as vascular endothelial growth factor (VEGF), are frequently up-regulated in tumors and create an immunosuppressive tumor microenvironment. Use of antiangiogenic drugs reverses this immunosuppression and can augment response to immunotherapy.

Lucitanib is an unlicensed medical product.