On December 3, 2018 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today data from the primary analysis of the Phase III HAVEN 2 study evaluating Hemlibra (emicizumab-kxwh) prophylaxis in children younger than 12 years of age with hemophilia A with factor VIII inhibitors, including longer follow-up for once-weekly dosing and new data for less frequent dosing schedules (every two weeks or every four weeks) (Press release, Genentech, DEC 3, 2018, View Source [SID1234531845]). These data from the largest pivotal study in children with hemophilia A with factor VIII inhibitors were presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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"Children with inhibitors are at increased risk of life-threatening bleeds and may experience frequent, repeated bleeding into joints," said Guy Young, M.D., director of Hemostasis and Thrombosis Center, Children’s Hospital Los Angeles, and professor of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, California. "These updated data from HAVEN 2 showed that the majority of children with hemophilia A with factor VIII inhibitors treated with emicizumab-kxwh had zero treated bleeds across three different dosing schedules, reinforcing the ability of this medicine to provide sustained, effective bleed control."

In updated results from the HAVEN 2 study with a median of 11 additional months of data, 76.9 percent (95 percent CI: 64.8; 86.5) of children with hemophilia A with factor VIII inhibitors treated with Hemlibra once weekly (n=65) experienced zero treated bleeds. Importantly, once-weekly Hemlibra showed a 99 percent (95 percent CI: 97.7; 99.4) reduction in treated bleeds compared to prior treatment with bypassing agents (BPAs) as prophylaxis (n=15) or on-demand (n=3) in a prospective intra-patient comparison. New data also showed that 90 percent (95 percent CI: 55.5; 99.7) of children with factor VIII inhibitors receiving Hemlibra every two weeks (n=10) and 60 percent (95 percent CI: 26.2; 87.8) of children receiving Hemlibra every four weeks (n=10) experienced zero treated bleeds, demonstrating clinically meaningful bleed control at both dosing schedules. No cases of thrombotic microangiopathy (TMA) or thrombotic events occurred. The most common adverse events (AEs) in the HAVEN 2 study primary analysis were consistent with those previously observed in the interim analyses.

"The updated analysis from the HAVEN 2 study supports the potential of Hemlibra to control bleeds at less frequent subcutaneous dosing, providing parents and their children more flexibility to choose a treatment schedule that is right for them," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Many children with hemophilia A with factor VIII inhibitors have already experienced the benefits of Hemlibra, and with these new positive data, we are confident that this treatment will continue to make a meaningful difference in their lives."

Hemlibra is approved in over 50 countries worldwide, including the U.S., EU member states and Japan, to treat people of all ages with hemophilia A with factor VIII inhibitors based on pivotal data that included interim results from the HAVEN 2 study. In October 2018, the U.S. Food and Drug Administration (FDA) also approved Hemlibra to treat people of all ages with hemophilia A without factor VIII inhibitors. Hemlibra is the only FDA-approved treatment for people with hemophilia A with and without factor VIII inhibitors that can be administered subcutaneously (under the skin) and at multiple dosing options (once weekly, every two weeks or every four weeks). Submissions to other regulatory authorities around the world are ongoing.

Hemlibra has been studied in one of the largest pivotal clinical trial programs in people with hemophilia A with and without factor VIII inhibitors, including four Phase III HAVEN studies (HAVEN 1, HAVEN 2, HAVEN 3 and HAVEN 4).

About HAVEN 2 (NCT02795767)

HAVEN 2 is a multicenter, open-label, clinical study in children younger than 12 years of age with hemophilia A with factor VIII inhibitors. The study is evaluating the efficacy, safety and pharmacokinetics of once-weekly, every two weeks or every four weeks subcutaneous administration of Hemlibra prophylaxis.

The HAVEN 2 primary analysis included 85 children (once-weekly dosing, n=65; every two week dosing, n=10; every four week dosing, n=10) with hemophilia A with factor VIII inhibitors. The median follow-up period for each cohort was 58 (range 17.9–92.6), 21.3 (range 18.6–24.1), and 19.9 (range 8.9–24.1) weeks, respectively. The prospective intra-patient comparison included 18 patients from the once-weekly cohort previously treated with BPAs either as prophylaxis (n=15) or on-demand (n=3) as part of a non-interventional study.

The study met its primary endpoint and key secondary endpoints. Data presented at the 60th ASH (Free ASH Whitepaper) Annual Meeting showed:

HAVEN 2 (NCT02795767)
Hemlibra prophylaxis 1.5 mg/kg QW
(Arm A; n=65)*

Annualized bleeding rate [ABR] †
(95% CI)

Median ABR
(Interquartile range; IQR)

Treated bleeds (primary endpoint)**
0.3
(0.17; 0.50)

0.0
(0.00; 0.00)

All bleeds
3.2
(1.94; 5.22)

0.6
(0.00; 2.92)

Treated spontaneous bleeds
0.0
(0.01; 0.10)

0.0
(0.00; 0.00)

Treated joint bleeds
0.2
(0.08; 0.29)

0.0
(0.00; 0.00)

Treated target joint bleeds
Not estimable

0.0
(0.00; 0.00)

*Efficacy assessment was conducted only in patients aged <12 years who had spent at least 12 weeks on the study. Excludes three patients aged >12 years.

A loading dose of 3 mg/kg Hemlibra was given for four weeks followed by the maintenance dose listed.

† Estimated using negative binomial regression

**In patients receiving Hemlibra once weekly (Arm A), 76.9% (95% CI, 64.8; 86.5) experienced zero treated bleeds and 23.1% experienced 1–3 treated bleeds.

Hemlibra prophylaxis 3 mg/kg
Q2W
(Arm B; n=10)*

Hemlibra prophylaxis 6 mg/kg
Q4W
(Arm C; n=10)*

ABR (95% CI) †

0.2
(0.03; 1.72)

2.2
(0.69; 6.81)

Median ABR (IQR)
0.0
(0.00; 0.00)

0.0
(0.00; 3.26)

% patients with zero treated
bleeds
(95% CI)

90.0%
(55.5; 99.7)

60.0%
(26.2; 87.8)

% patients with 1-3 treated
bleeds
(95% CI)

10.0%
(0.3; 44.5)

40.0%
(12.2; 73.8)

*A loading dose of 3 mg/kg Hemlibra was given for four weeks followed by the maintenance dose listed.

† Estimated using negative binomial regression

The most common adverse reactions occurring in 10 percent or more of children treated with Hemlibra were common cold symptoms (nasopharyngitis; 37.5 percent), injection site reactions (29.5 percent), fever (pyrexia; 23.9 percent), upper respiratory tract infection (23.9 percent), cough (23.9 percent), diarrhea (15.9 percent), vomiting (15.9 percent), headache (14.8 percent), contusion (12.5 percent), fall (12.5 percent) and influenza (10.2 percent). No cases of TMA or thrombotic events occurred. Four patients tested positive for anti-drug antibodies (ADAs) to Hemlibra. Of these patients, two had ADAs with neutralizing potential based on reduced Hemlibra levels. As previously reported, the ADA in one of these patients resulted in reduced efficacy of Hemlibra and led to discontinuation of treatment. The other patient had no bleeds as of the clinical cut-off date of the study.

About Hemlibra

Hemlibra is a bispecific factor IXa- and factor X-directed antibody. It is designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and restore the blood clotting process for hemophilia A patients. Hemlibra is a prophylactic (preventative) treatment that can be administered by an injection of a ready-to-use solution under the skin (subcutaneously) once weekly, every two weeks or every four weeks. Hemlibra was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed globally by Chugai, Roche and Genentech.

Hemlibra U.S. Indication

Hemlibra is a prescription medicine used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children, ages newborn and older, with hemophilia A with or without factor VIII inhibitors.

Important Safety Information

What is the most important information to know about Hemlibra?

Hemlibra increases the potential for blood to clot. Patients should carefully follow their healthcare provider’s instructions regarding when to use an on-demand bypassing agent or factor VIII, and the dose and schedule to use for breakthrough bleed treatment. Hemlibra may cause the following serious side effects when used with activated prothrombin complex concentrate (aPCC; FEIBA), including:

Thrombotic microangiopathy (TMA). This is a condition involving blood clots and injury to small blood vessels that may cause harm to one’s kidneys, brain, and other organs. Patients should get medical help right away if they have any of the following signs or symptoms during or after treatment with Hemlibra:
confusion
weakness
swelling of arms and legs
yellowing of skin and eyes
stomach (abdomen) or back pain
nausea or vomiting
feeling sick
decreased urination
Blood clots (thrombotic events). Blood clots may form in blood vessels in the arm, leg, lung, or head. Patients should get medical help right away if they have any of these signs or symptoms of blood clots during or after treatment with Hemlibra:
swelling in arms or legs
pain or redness in the arms or legs
shortness of breath
chest pain or tightness
fast heart rate
cough up blood
feel faint
headache
numbness in the face
eye pain or swelling
trouble seeing
If aPCC (FEIBA) is needed, patients should talk to their healthcare provider in case they feel they need more than 100 U/kg of aPCC (FEIBA) total.

Before using Hemlibra, patients should tell their healthcare provider about all of their medical conditions, including if they:

are pregnant or plan to become pregnant. It is not known if Hemlibra may harm an unborn baby. Females who are able to become pregnant should use birth control (contraception) during treatment with Hemlibra.
are breastfeeding or plan to breastfeed. It is not known if Hemlibra passes into breast milk.
Patients should tell their healthcare provider about all the medicines they take, including prescription medicines, over-the-counter medicines, vitamins, or herbal supplements. Patients should keep a list of them to show their healthcare provider and pharmacist when they get a new medicine.

How should patients use Hemlibra?

Patients should see the detailed "Instructions for Use" that comes with Hemlibra for information on how to prepare and inject a dose of Hemlibra, and how to properly throw away (dispose of) used needles and syringes.

Stop (discontinue) prophylactic use of bypassing agents the day before starting Hemlibra prophylaxis.
Patients may continue prophylactic use of factor VIII for the first week of Hemlibra prophylaxis.
What should patients know about lab monitoring?

Hemlibra may interfere with laboratory tests that measure how well blood is clotting and may cause a false reading. Patients should talk to their healthcare provider about how this may affect their care.

The most common side effects of Hemlibra include: redness, tenderness, warmth, or itching at the site of injection; headache; and joint pain.

These are not all of the possible side effects of Hemlibra. Patients should speak to their healthcare provider for medical advice about side effects.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Patients should not use Hemlibra for a condition for which it was not prescribed. Patients should not give Hemlibra to other people, even if they have the same symptoms that they have. It may harm them. Patients can ask their pharmacist or healthcare provider for information about Hemlibra that is written for health professionals.

Side effects may be reported to the FDA at (800) FDA-1088 or View Source Side effects may also be reported to Genentech at (888) 835-2555.

Please see the Hemlibra full Prescribing Information and Medication Guide for more important safety information including Serious Side Effects.

About hemophilia A

Hemophilia A is an inherited, serious disorder in which a person’s blood does not clot properly, leading to uncontrolled and often spontaneous bleeding. Hemophilia affects around 20,000 people in the United States, with hemophilia A being the most common form and approximately 50-60 percent of people living with a severe form of the disorder.

People with hemophilia A either lack or do not have enough of a clotting protein called factor VIII. In a healthy person, when a bleed occurs, factor VIII brings together the clotting factors IXa and X, which is a critical step in the formation of a blood clot to help stop bleeding. Depending on the severity of their disorder, people with hemophilia A can bleed frequently, especially into their joints or muscles. These bleeds can present a significant health concern as they often cause pain and can lead to chronic swelling, deformity, reduced mobility and long-term joint damage.

A serious complication of treatment is the development of inhibitors to factor VIII replacement therapies. Inhibitors are antibodies developed by the body’s immune system that bind to and block the efficacy of replacement factor VIII, making it difficult, if not impossible, to obtain a level of factor VIII sufficient to control bleeding.

On December 3, 2018 TRIGR Therapeutics, Inc. ("TRIGR"), and ABL Bio, Inc. ("ABL"), reported that they have entered into a collaboration and license agreement for TR009 (formerly known as ABL001 or NOV1501), an ABL developed bispecific antibody candidate targeting two important angiogenic factors, VEGF and DLL4 (Press release, TRIGR Therapeutics, DEC 3, 2018, View Source [SID1234531844]). The license agreement is exclusive and global, excluding the Republic of Korea for all oncology indications and excluding the Republic of Korea and Japan for all ophthalmology indications. This agreement is in addition to the recently announced agreement whereby TRIGR licensed pre-clinical immune engaging bispecific antibodies from ABL.

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TR009 is currently in a dose escalation Phase 1a study being conducted at the Samsung Medical Center in South Korea. The phase 1a study is sponsored by ABL and National OncoVenture (NOV), a South Korean government funded oncology drug development program. A phase 1b study looking to combine TR009 with chemotherapy and a checkpoint inhibitor is expected to commence in the latter part of 2019.

To date, 12 patients have been dosed with TR009 and no dose-limiting toxicities (DLTs) have been reported. Based on preliminary patient data, TR009 single agent clinical activity has been demonstrated across all dose levels among heavily pre-treated (5+ lines of prior therapy) cancer patients with solid tumors including gastric, colon, GIST, and ovarian cancers. At the mid-dose level cohort, more than half of the patients have experienced durable clinical benefit in terms of tumor stabilization (stable disease).

Under the terms of the agreement, TRIGR is responsible for global Phase 2 and subsequent clinical development and commercialization activities for TR009 for all oncology indications. ABL will receive an upfront payment of $5 million and is eligible to receive up to $405 million in regulatory and sales milestones and royalties on oncology sales of TR009 outside of the Republic of Korea. For ophthalmology indications, TRIGR is responsible for all development and commercialization within its territories. ABL is eligible to receive up to $185 million in milestone payments and royalties on TR009 ophthalmology sales outside of the Republic of Korea and Japan.

"We are delighted to expand our relationship with ABL," said George Uy, CEO of TRIGR. "Combining both companies’ core competencies and resources will optimize our chances of success in developing this novel cancer therapy. ABL has an outstanding track record of bispecific antibody research and development with extensive capabilities in antibody engineering and validation. We are excited by the promising clinical activity that TR009 has shown thus far, especially in heavily pre-treated patients with gastric and colon cancers, which is a key differentiator of this program. Based on our pre-clinical validation and additional biomarker work, our short-term strategy for TR009 is to pursue an accelerated approval pathway in Asia and we intend to approach both Chinese (NMPA) and Japanese regulators upon completion of our Phase 1a study in mid-2019. We also plan to simultaneously seek regulatory guidance from the FDA and EMEA for the registration of TR009 in solid tumor patients in the US and Europe."

"We are very pleased to enter into this agreement with our partners at TRIGR, a premier team that is highly experienced in taking anti-cancer drugs through clinical development and commercialization," said Sang Hoon Lee, CEO of ABL. "The dual VEGF/DLL4 bispecific antibodies currently in clinical development have all shown meaningful clinical activity even in patients who have failed or progressed on multiple lines of prior chemotherapy and VEGF-directed therapies such as Avastin and Cyramza. Across all trials, over 140 patients have been treated in monotherapy or in combination settings and we are seeing clinical benefit rates of between 50-85%. This is clearly exciting news for cancer patients worldwide."

Anti-angiogenic therapy is a cornerstone in cancer care, with sales of Avastin (an anti-VEGF antibody, Roche) and Cymraza (an anti-VEGF-R2 antibody, Eli Lilly) comprising approximately $7.5 billion in 2017. Although this class of drugs has proven survival benefits, resistance is creating the need for alternative regimens. Dual blockade of both VEFG and DLL4 is emerging as the next frontier of angiogenic therapy as the combination of these 2 mechanisms has been shown to overcome VEGF inhibitor resistance. There are 3 programs currently in clinical development targeting anti-VEGF/DLL4: AbbVie’s ABT-165 (Nasdaq: ABBV) which has recently entered Phase 2 in colorectal cancer, Oncomed’s OMP305B83 (Nasdaq: OMED) in Phase 1b in platinum-resistant ovarian cancer, and TRIGR’s TR009 in Phase 1a.

On December 3, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported its the long-term results of the Phase 3 ALCYONE study demonstrating that the addition of Darzalex (daratumumab) to bortezomib , melphalan and prednisone (VMP) continued to show significant improvement in progression-free survival (PFS) in patients recently diagnosed with multiple myeloma who are ineligible for autologous stem cell transplantation (GATS) (Press release, Johnson & Johnson, DEC 3, 2018, View Source [SID1234531843]). 1 These data ( Summary No. 156 ), as well as the updates of the LYRA ( Summary No. 152 ) and GRIFFIN ( Summary No. 151)) Phase 2 in patients with multiple myeloma were presented in an oral session on data presentation abstracts at the 60 th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) that was held in San Diego, California.

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Long-term results of the ALCYONE Phase 3 trial for first-line combined treatment with daratumumab 1

With a median follow-up of 27.8 months, the results of the study showed that the addition of daratumumab to the combination of bortezomib, melphalan and prednisone (VMP) reduced the risk of disease progression by 57 percent. or death, in comparison with treatment based solely on the VMP combination (risk ratio [RR] = 0.43, 95 percent confidence interval [CI] 0.35-0.54, p <0, 0001). 1 The combination of daratumumab-VMP resulted in a 24-month PHC rate of 63 percent, compared to 36 percent for VMP alone. 1 The median PFS for the combination of araratumumab-VMP has not yet been reached, and the control group (PMV alone) had a median PFS of 19.1 months.1 In addition, a significantly higher overall response rate (91 percent vs. 74 percent, respectively) was observed for the combination based on daratumumab, compared with the single VMP. 1 The combination of daratumumab-VMP achieved faster responses, with a significant improvement in the rate of very good partial response or higher rate (73 percent versus 50 percent), and a strict complete response rate more than twice as high ( 22 percent vs. 8 percent) to that of the VMP alone. 1 The combination of aratumumab-VMP induced a higher rate of long-term residual residual disease negativity compared to VMP alone (10 percent versus 2 percent, respectively).1 The main results previously announced in this study motivated the European Commission to approve daratumumab in combination with MPV for patients with newly diagnosed multiple myeloma who are not eligible for GATS.

Long-term data from pivotal ALCYONE trial show that combined treatment with daratumumab continued to demonstrate improved progression-free survival and response rates in newly diagnosed patients with multiple myeloma, including patients older people less likely to respond to treatment, "said Meletios A. Dimopoulos, MD, professor and chair of the Clinical Therapies Department at the Faculty of Medicine at the National Capodistrian University of Athens, Greece, and principal investigator. These promising results support the use of daratumumab earlier in the treatment paradigm,

In the ALCYONE study, the most common grade 3/4 adverse events that occurred during treatment with daratumumab-VMP starting in cycle 10 included anemia (4 percent), neutropenia (2 percent), and bronchitis (1 percent). 1 No new safety concerns were observed, and Grade 3/4 infections remained treatable. 1

Data from LYRA and GRIFFIN Phase 2 trials support the efficacy and safety profile of daratumumab in newly diagnosed patients, including those who are eligible for high-dose treatment / GATS, and in patients in relapse 2 , 3

Response rates from the LYRA Phase 2 study were presented for the experimental use of daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients recently diagnosed with multiple and relapsed myeloma. 2 The overall response rate and TBRP or upper rate in 86 newly diagnosed patients, who were 79 and 44 percent, respectively, after 4 cycles, increased to 81 and 56 percent, respectively, at the end of the initial treatment period (average of 6 cycles). 2In addition, the TBRP or higher rate in 14 patients with recurrent multiple myeloma, which was 57 percent after 4 cycles, then increased to 64 percent at the end of induction, while the rate overall response remained stable at 71 percent (average of 7.5 cycles). 2 The 18-month PHC rate was 78 percent in newly diagnosed and ineligible autologous patients, compared with 53 percent in relapsed patients. 2 In addition, this study, which evaluated the fractionation of the first dose of daratumumab to reduce infusion duration on Day 1 of Cycle 1 (C1D1), demonstrated a safety profile consistent with previous studies. . 2Infusion reactions occurred in 49 percent of patients with C1D1, compared to four percent of patients on Day 2 of Cycle 1 (C1D2). Fifty-four percent of newly diagnosed patients experienced infusion reactions, the most common being: chills (14 percent), dyspnoea, pruritus, and nausea (8 percent each), as well as coughing. (7 percent). Fifty-seven percent of relapsed patients experienced infusion-related reactions, the most common of which were: cough (21 percent), hyperhidrosis, dyspnea and chills (7 percent each). Only two patients had a grade 3 infusion reaction, and no grade 4 infusion reaction occurred. has been noted. No interruption of taking daratumumab was necessary because of an infusion reaction. The median infusion time was 4.5 hours at C1D1, compared to 3.8 hours at C1D2.2 Grade 3/4 adverse events that occurred during treatment were reported in 56 percent of patients, the most common (≥10 percent) being neutropenia (13 percent). 2

Data presented in the GRIFFIN Phase 2 study evaluated daratumumab in combination with bortezomib, lenalidomide and dexamethasone (VRd) in a safety group of 16 patients recently diagnosed with multiple myeloma, eligible for high dose treatment and GATS. 3 The results showed that at the end of the GATS consolidation treatment, all patients who participated in the safety preparatory period achieved a TBRP or higher rate, and 63 percent of them achieved complete response (CR) or higher, with 25 percent of patients having achieved SCR. 3In addition, 94 percent of patients remained without progression during the study, at a median follow-up of 16.8 months. 3 In addition, 8 out of 16 patients (50 percent) were negative for the residual disease test, at a level of 10 -5 at the end of consolidation. 3 During grade 3/4 treatment, fourteen patients (88 percent) reported adverse events, including 10 cases (63 percent of patients) related to daratumumab treatment. 3The most common adverse events (≥10 per cent) that occurred during grade 3/4 treatment were neutropenia, pneumonia, thrombocytopenia, lymphopenia, febrile neutropenia, leukopenia, rash, and hypophosphatemia. 3 Thirteen patients (81 percent) had the following infections, all grades: upper respiratory infection (six patients), pneumonia (four patients), bronchitis (two patients), otitis and viral gastroenteritis (two patients each) ). 3 No deaths due to serious adverse events were reported and no patient had to discontinue treatment due to an adverse event. 3These data suggest that induction therapy with daratumumab has no negative impact on stem cell mobilization. All 16 patients had successful stem cell mobilization, followed by GATS. 3

"Daratumumab offers a consistent clinical benefit across multiple therapeutic lines for multiple myeloma, and positive data from the ALCYONE, LYRA, and GRIFFIN studies add to the solid body of evidence supporting daratumumab-based protocols," said Dr. Dr. Catherine Taylor, Head of Hematology Treatments for Europe, Middle East and Africa (EMEA) at Janssen-Cilag Limited. "These are important findings for patients that provide additional information about the most effective methods of managing care," she added.

#END#

About the ALCYONE 4 trial

The randomized, open-label, multi-center Phase 3 ALCYONE (MMY3007) study enrolled 706 patients newly diagnosed with multiple myeloma and ineligible for high-dose GSC chemotherapy. The median age of these patients was 71 years (age range: 40-93). Patients were randomized to receive nine cycles of daratumumab combined with VMP, or VMP alone. In the daratumumab-VMP group, patients received 16 mg / kg of daratumumab once a week for the first week (cycle 1) and then once every three weeks (cycles 2-9). After nine cycles, they continued to receive 16 mg / kg of daratumumab once every four weeks until disease progression.

About the LYRA 5 trial

The ongoing, single-arm, open-label, multi-center LYRA (MMY2012) Phase 2 study enrolled 100 adult patients 18 years of age and older. Patients received 4-8 cycles of combination therapy with daratumumab, including an oral dose of cyclophosphamide 300 mg / m 2 on days 1, 8, 15 and 22; a subcutaneous dose of bortezomib 1.5 mg / m 2 on days 1, 8 and 15; a weekly oral or intravenous dose of dexamethasone 40 mg every 28 days. Daratumumab was administered at 8 mg / kg intravenously at days 1 and 2 of cycle 1, at a weekly dose of 16 mg / kg from cycle 1, at day 8 during cycle 2, at a dose of 16 mg / kg every 2 weeks at cycles 3-6, and at a dose of 16 mg / kg every 4 weeks at cycles 7-8. After the induction treatment, the patients were able to receive a GATS. All patients received 12 cycles of maintenance treatment of 16 mg / kg intravenously every 4 weeks.

About the GRIFFIN 6 trial

The randomized, open-label Phase II GRIFFIN study (MMY2004) recruited and treated more than 200 adults between 18 and 70 years of age, eligible for high-dose treatment / GATS, 7including 16 patients in the safety preparatory phase to evaluate the potential dose limiting toxicities during cycle 1 of daratumumab combined with VRd. The latter patients were treated with four cycles of daratumumab and VRd infusion every 21 days, followed by stem cell mobilization, high-dose treatment and GATS; two consolidation cycles with daratumumab and VRd; as well as maintenance therapy with daratumumab and lenalidomide at cycles 7-32. During induction and consolidation therapy (cycles 1-6), patients received an oral dose of 25 mg lenalidomide on days 1-14, a dose of 1.3 mg / m 2bortezomib subcutaneously on days 1, 4, 8 and 11 and a dose of 20 mg dexamethasone on days 1, 2, 8, 9, 15 and 16 every 21 days. An infusion of daratumumab 16 mg / kg IV was administered on days 1, 8 and 15 of cycles 1-4 and day 1 of cycles 5-6. During the maintenance period (cycles 7-32), patients received a daily dose of 10 mg lenalidomide (15 mg from cycle 10, if tolerated) on days 1-21 every 28 days, and an injection of daratumumab 16 mg / kg every 56 days; this treatment was adjusted every 28 days. Lenalidomide maintenance therapy can be extended beyond cycle 32, according to the local care protocol.7

About Daratumumab

Daratumumab is an advanced biological product targeting the CD38 gene, a surface protein that is overexpressed in multiple multiple myeloma cells, regardless of the stage of the disease. 8 The Daratumumab induce the death of tumor cells via multiple mechanisms of action immunologically mediated, including complement-dependent cytotoxicity (CDC), an antibody-dependent cellular cytotoxicity (CBDC) and dependent cellular phagocytosis of antibody (PCDA) and via apoptosis, during which a series of molecular steps inside the cell leads to the death of the cell. 9A subset of suppressive cells derived from myeloid, CD38 + regulatory T cells and CD38 + B cells was reduced by daratumumab. 9 Daratumumab is being evaluated as part of a comprehensive clinical development program covering a range of treatment protocols for multiple myeloma, including first-line treatment, or recurrence. 10,11,12,13,14,15,16,17 Additional studies are underway or planned to evaluate the potential of this treatment targeting other malignant and pre-malignant haematological conditions in which the CD38 gene is expressed, such as indolent myeloma. 18,19For more information, please visit www.clinicaltrials.gov .

In Europe, daratumumab is indicated for use in combination with bortezomib, melphalan and prednisone for the treatment of newly diagnosed adult patients with multiple myeloma who are ineligible for autologous stem cell transplantation as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, previously treated with a proteasome inhibitor and an immunomodulatory agent, and who experienced disease progression during the last treatment, and in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, and for the treatment of adult patients with multiple myeloma who have benefited fromat least one prior treatment.9 For more information on daratumumab, please see the summary of product characteristics at View Source .

In August 2012 , Janssen Biotech, Inc. and Genmab A / S entered into a worldwide agreement granting Janssen an exclusive license to develop, manufacture and market daratumumab. 20

About multiple myeloma

Multiple myeloma is an incurable cancer of the blood that is found in the bone marrow. The disease is characterized by excessive proliferation of plasma cells. 21 More than 45,000 new cases of multiple myeloma were diagnosed in Europe in 2016, and more than 29,000 patients died. 22 Up to half of newly diagnosed patients do not achieve five-year survival, 23 and nearly 29% of multiple myeloma patients die within one year of diagnosis. 24

Although the treatment may lead to remission, in most cases a relapse will occur because no cure is currently possible. 25 A refractory multiple myeloma is characterized by the fact that the patient’s disease progresses within 60 days following the last treatment. 26,27 A recurrent cancer is characterized by the fact that the disease recurs after a period of initial, partial or complete remission. 28While some patients with multiple myeloma have absolutely no symptoms, the majority of them are diagnosed with symptoms that may include bone problems, low blood counts, increased calcium levels, infections or kidney problems. 29 Patients who have relapsed after treatment with standard therapy, including inhibitors of the proteasome and immunumodulateurs agents have poor prognosis and few treatment options. 30

On December 3, 2018 Amphivena Therapeutics, Inc., reported a privately held biotechnology company developing AMV564, a CD33/CD3 T cell engager for the treatment of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), presented Saturday night in a poster presentation at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) first-in-human Phase 1 clinical data that demonstrate that in patients with relapsed/refractory AML, AMV564 is well-tolerated and has anti-leukemic activity through T-cell engagement (Press release, Amphivena Therapeutics, DEC 3, 2018, View Source [SID1234531842]). The data from this ongoing dose escalation trial further show that AMV564 has a unique PK profile with a gradual increase in drug exposures that mitigates cytokine release syndrome (CRS).

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"The ASH (Free ASH Whitepaper) data reports continued evidence of single-agent clinical activity in heavily pre-treated patients with refractory/relapsed AML. AMV564 has been well-tolerated and has the potential to be safely combined with other agents. Importantly, its 2-day half-life supports intermittent dosing which differentiates AMV564 from other T cell engagers in development for myeloid malignancies," said Eric J. Feldman, M.D., Amphivena’s Chief Medical Officer.

The poster highlights the safety and efficacy data on 26 evaluable patients, as follows:

Complete and partial responses (CRi, PR) observed in patients dosed at 100 mcg with a 14-day dosing regimen
No dose-limiting toxicity through the 150 mcg cohort, with a 0% 30-day mortality rate
No Grade 2+ CRS with a lead-in dose and no Grade 3+ CRS
Novel pharmacokinetic profile with a 2-day terminal half-life
A seamless Phase 1/2 study is ongoing at six centers in the U.S.

On December 3, 2018 Genprex, Inc. (NASDAQ: GNPX), a clinical-stage gene therapy company developing a new approach to treating cancer based upon a novel proprietary technology platform, reported that its Chairman and Chief Executive Officer, Rodney Varner, will present at the 11th annual LD Micro Main Event at the Luxe Sunset Boulevard Hotel in Los Angeles, CA (Press release, Genprex, DEC 3, 2018, View Source [SID1234531841]).

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Genprex is scheduled to present on Wed., Dec. 5, 2018, at 10:30 a.m. PST. Genprex management will also attend one-on-one meetings with institutional investors throughout the day.

The LD Micro Main Event is the largest independent conference for small/micro-cap companies and will feature 250 companies presenting to an audience of over 1,200 attendees.