On December 5, 2017 Eli Lilly and Company (NYSE: LLY) reported top-line results from its Phase 3 RAINFALL study of CYRAMZA (ramucirumab) in combination with cisplatin and capecitabine or 5-FU (5-fluorouracil) in the first-line treatment of patients with HER2-negative metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (Press release, Eli Lilly, DEC 8, 2017, View Source [SID1234522477]). The trial met its primary endpoint of progression-free survival (PFS) but did not improve overall survival (OS), a secondary endpoint. The results will be submitted for presentation at a future medical meeting.

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The safety profile observed in the RAINFALL study was consistent with what has been previously observed for ramucirumab. Grade ≥3 adverse events occurring at a rate of five percent or greater and that were higher on the ramucirumab-plus-cisplatin-and-capecitabine/5-FU arm compared to the placebo-plus-cisplatin-and-capecitabine/5-FU arm were hypertension, hand-foot syndrome, and fatigue.

"While we hoped that the positive PFS outcome would have translated into an OS benefit, these RAINFALL results highlight the challenges associated with improving outcomes for people with advanced gastric cancer," said Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology. "This is underscored by the fact that there have been no major advances over standard chemotherapy in the first-line HER2-negative gastric cancer treatment setting in the last decade."

Dr. Garraway added, "Lilly is deeply committed to patients with this aggressive disease, and CYRAMZA remains a standard of care in the second-line treatment paradigm for advanced gastric cancer patients around the world. We thank the patients, their caregivers and investigators for their support of and participation in the RAINFALL study."

The company does not intend to seek regulatory approval based on the results of the RAINFALL study. The outcome of RAINFALL does not have any impact on current ramucirumab approvals.

After becoming the first FDA-approved agent to treat advanced gastric cancer after prior chemotherapy in 2014 based on two pivotal Phase 3 studies, ramucirumab is now a standard of care in this setting around the world. This is supported by global and local treatment guidelines, including NCCN, JGCA and ESMO (Free ESMO Whitepaper).

Overall, there have been six positive Phase 3 trials of ramucirumab to date. Previously completed Phase 3 studies of ramucirumab have demonstrated benefit in advanced forms of gastric, non-small cell lung and colorectal cancer – three of the world’s leading causes of cancer-related death. An ongoing Phase 3 trial in advanced urothelial carcinoma has also met its primary endpoint of PFS; those initial data were presented at the ESMO (Free ESMO Whitepaper) 2017 Congress and OS data are expected in mid-2018. Two other ongoing Phase 3 studies of ramucirumab – in hepatocellular carcinoma and EGFR-positive non-small cell lung cancer – are ongoing, with expected data readouts in 2018.

Notes to Editors

About RAINFALL
RAINFALL is a global, randomized, double-blinded, placebo-controlled Phase 3 study of ramucirumab in combination with cisplatin and capecitabine as a first-line treatment in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Study participants unable to take capecitabine (tablets) were given 5-fluorouracil (5-FU).

Initiated in 2015, the study enrolled 645 patients across 19 countries in North America, Asia (Japan), Europe and Latin America. The primary endpoint of the RAINFALL trial is progression-free survival and key secondary endpoints include: overall survival; objective response rate; and safety.

About Gastric Cancer
Gastric cancer, also known as stomach cancer, is a major global health problem. Globally, it is the fifth most common cancer in the world, with one million new cases annually.1 Gastric cancer originates in the stomach. Cancer cells typically develop slowly and symptoms often do not appear until the disease is advanced and has already spread to other organs such as the liver, lungs and bones.2,3 Stomach cancer is the third leading cause of cancer deaths in the world, resulting in 723,000 deaths each year.1 The five-year survival rate for stomach cancer is 31 percent and five percent for advanced cases.4

Stomach cancer is much more common in the Far East than in the Western world.1 In the U.S., it is estimated that approximately 28,000 people will be diagnosed with stomach cancer and nearly 11,000 people will die from this type of cancer in 2017.5 In Japan, the incidence of stomach cancer is high. Of all cancers in Japan, stomach cancer is the second most common and it is the second-leading cause of cancer-related deaths, affecting approximately 108,000 people and killing approximately 52,000.

About Angiogenesis and VEGF Protein
Angiogenesis is the process of making new blood vessels. In a person with cancer, angiogenesis creates new blood vessels that give a tumor its own blood supply, allowing it to grow and spread.

Some tumors create proteins called VEGF. These proteins attach to the VEGF receptors of blood vessel cells causing new blood vessels to form around the tumors, enabling growth. Blocking the VEGF protein from linking to the blood vessels helps to inhibit tumor growth by slowing angiogenesis and the blood supply that feeds tumors. Of the three known VEGF receptors, VEGF Receptor 2 is linked most closely to VEGF-induced tumor angiogenesis.

About CYRAMZA (ramucirumab)
In the U.S., CYRAMZA (ramucirumab) is approved for use as a single agent or in combination with paclitaxel as a treatment for people with advanced or metastatic gastric (stomach) or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy. It is also approved in combination with docetaxel as a treatment for people with metastatic non-small cell lung cancer (NSCLC) whose cancer has progressed on or after platinum-based chemotherapy. Additionally, it is approved with FOLFIRI as a treatment for people with metastatic colorectal cancer (mCRC) whose cancer has progressed on or after therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

Ramucirumab is being investigated in a broad global development program that has enrolled more than 10,000 patients across more than 70 trials worldwide. There are several studies underway or planned to investigate ramucirumab as a single agent and in combination with other anti-cancer therapies for the treatment of multiple tumor types.

Ramucirumab is an antiangiogenic therapy. It is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist that specifically binds and blocks activation of VEGF Receptor 2 by blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D. Ramucirumab inhibited angiogenesis in an in vivo animal model.

INDICATIONS

Gastric Cancer
CYRAMZA, as a single agent or in combination with paclitaxel, is indicated for the treatment of patients with advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.

Non-Small Cell Lung Cancer
CYRAMZA, in combination with docetaxel, is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving CYRAMZA.

Colorectal Cancer
CYRAMZA, in combination with FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

IMPORTANT SAFETY INFORMATION FOR CYRAMZA

WARNING: HEMORRHAGE, GASTROINTESTINAL PERFORATION, AND
IMPAIRED WOUND HEALING

Hemorrhage: CYRAMZA increased the risk of hemorrhage and gastrointestinal
hemorrhage, including severe and sometimes fatal hemorrhagic events. Permanently
discontinue CYRAMZA in patients who experience severe bleeding.

Gastrointestinal Perforation: CYRAMZA can increase the risk of gastrointestinal
perforation, a potentially fatal event. Permanently discontinue CYRAMZA in patients who
experience a gastrointestinal perforation.

Impaired Wound Healing: Impaired wound healing can occur with antibodies inhibiting
the VEGF pathway. Discontinue CYRAMZA therapy in patients with impaired wound
healing. Withhold CYRAMZA prior to surgery and discontinue CYRAMZA if a patient
develops wound healing complications.
Warnings and Precautions

Hemorrhage

In study 1, which evaluated CYRAMZA as a single agent in advanced gastric cancer, the incidence of severe bleeding was 3.4% for CYRAMZA and 2.6% for placebo. In study 2, which evaluated CYRAMZA plus paclitaxel in advanced gastric cancer, the incidence of severe bleeding was 4.3% for CYRAMZA plus paclitaxel and 2.4% for placebo plus paclitaxel. Patients with gastric cancer receiving nonsteroidal anti-inflammatory drugs (NSAIDs) were excluded from enrollment in studies 1 and 2. In study 3, which evaluated CYRAMZA plus docetaxel in metastatic non-small cell lung cancer (NSCLC), the incidence of severe bleeding was 2.4% for CYRAMZA plus docetaxel and 2.3% for placebo plus docetaxel. Patients with NSCLC receiving therapeutic anticoagulation or chronic therapy with NSAIDs or other antiplatelet therapy other than once-daily aspirin or with radiographic evidence of major airway or blood vessel invasion or intratumor cavitation were excluded from study 3. In study 4, which evaluated CYRAMZA plus FOLFIRI in metastatic colorectal cancer, the incidence of severe bleeding was 2.5% for CYRAMZA plus FOLFIRI and 1.7% for placebo plus FOLFIRI. Permanently discontinue CYRAMZA in patients who experience severe bleeding.
Arterial Thromboembolic Events (ATEs)

Serious, sometimes fatal, ATEs including myocardial infarction, cardiac arrest, cerebrovascular accident, and cerebral ischemia occurred in clinical trials. Permanently discontinue CYRAMZA in patients who experience a severe ATE.
Hypertension

An increased incidence of severe hypertension occurred in patients receiving CYRAMZA as a single agent (8%) as compared to placebo (3%), in patients receiving CYRAMZA plus paclitaxel (15%) as compared to placebo plus paclitaxel (3%), and in patients receiving CYRAMZA plus docetaxel (6%) as compared to placebo plus docetaxel (2%), and in patients receiving CYRAMZA plus FOLFIRI (11%) as compared to placebo plus FOLFIRI (3%). Monitor blood pressure every 2 weeks or more frequently as indicated during treatment. Temporarily suspend CYRAMZA for severe hypertension until medically controlled. Permanently discontinue CYRAMZA if medically significant hypertension cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis or hypertensive encephalopathy.
Infusion-Related Reactions (IRRs)

Prior to the institution of premedication recommendations across clinical trials of CYRAMZA, IRRs occurred in 6 out of 37 patients (16%), including 2 severe events. The majority of IRRs across trials occurred during or following a first or second CYRAMZA infusion. Monitor patients during the infusion for signs and symptoms of IRRs in a setting with available resuscitation equipment. Immediately and permanently discontinue CYRAMZA for grade 3 or 4 IRRs.
Gastrointestinal Perforations

Four of 570 patients (0.7%) who received CYRAMZA as a single agent in advanced gastric cancer clinical trials experienced gastrointestinal perforation. In study 2, the incidence of gastrointestinal perforation was 1.2% for CYRAMZA plus paclitaxel as compared to 0.3% for placebo plus paclitaxel. In study 3, the incidence of gastrointestinal perforation was 1% for CYRAMZA plus docetaxel as compared to 0.3% for placebo plus docetaxel. In study 4, the incidence of gastrointestinal perforation was 1.7% for CYRAMZA plus FOLFIRI and 0.6% for placebo plus FOLFIRI. Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation.
Impaired Wound Healing

CYRAMZA has not been studied in patients with serious or nonhealing wounds. CYRAMZA has the potential to adversely affect wound healing. Discontinue CYRAMZA therapy in patients with impaired wound healing. Withhold CYRAMZA prior to surgery. Resume CYRAMZA following the surgical intervention based on clinical judgment of adequate wound healing. If a patient develops wound healing complications during therapy, discontinue CYRAMZA until the wound is fully healed.
Clinical Deterioration in Child-Pugh B or C Cirrhosis

Clinical deterioration, manifested by new onset or worsening encephalopathy, ascites, or hepatorenal syndrome, was reported in patients with Child-Pugh B or C cirrhosis who received single-agent CYRAMZA.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

RPLS has been reported at a rate of < 0.1% in clinical studies with CYRAMZA. Discontinue CYRAMZA in patients who develop RPLS. Symptoms may resolve or improve within days, although some patients with RPLS can experience ongoing neurologic sequelae or death.
Proteinuria Including Nephrotic Syndrome

In study 4, severe proteinuria occurred more frequently in patients treated with CYRAMZA plus FOLFIRI compared to patients receiving placebo plus FOLFIRI. Severe proteinuria was reported in 3% of patients treated with CYRAMZA plus FOLFIRI (including 3 cases [0.6%] of nephrotic syndrome) compared to 0.2% of patients treated with placebo plus FOLFIRI. Monitor proteinuria by urine dipstick and/or urinary protein creatinine ratio for the development of worsening of proteinuria during CYRAMZA therapy. Withhold CYRAMZA for urine protein levels that are ≥2 g over 24 hours. Reinitiate CYRAMZA at a reduced dose once the urine protein level returns to < 2 g over 24 hours. Permanently discontinue CYRAMZA for urine protein levels > 3 g over 24 hours or in the setting of nephrotic syndrome.
Thyroid Dysfunction

Monitor thyroid function during treatment with CYRAMZA. In study 4, the incidence of hypothyroidism reported as an adverse event was 2.6% in the CYRAMZA plus FOLFIRI-treated patients and 0.9% in the placebo plus FOLFIRI-treated patients.
Embryofetal Toxicity

Based on its mechanism of action, CYRAMZA can cause fetal harm when administered to pregnant women. Animal models link angiogenesis, VEGF, and VEGF Receptor 2 (VEGFR2) to critical aspects of female reproduction, embryofetal development, and postnatal development. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CYRAMZA and for at least 3 months after the last dose of CYRAMZA.
Most Common Adverse Reactions—Single Agent

The most commonly reported adverse reactions (all grades; grade 3/4) occurring in ≥5% of patients receiving CYRAMZA and ≥2% higher than placebo in study 1 were hypertension (16% vs 8%; 8% vs 3%), diarrhea (14% vs 9%; 1% vs 2%), headache (9% vs 3%; 0% vs 0%), and hyponatremia (6% vs 2%; 3% vs 1%).
The most common serious adverse events with CYRAMZA in study 1 were anemia (3.8%) and intestinal obstruction (2.1%). Red blood cell transfusions were given to 11% of CYRAMZA-treated patients vs 8.7% of patients who received placebo.
Clinically relevant adverse reactions reported in ≥1% and < 5% of CYRAMZA-treated patients vs placebo in study 1 were: neutropenia (4.7% vs 0.9%), epistaxis (4.7% vs 0.9%), rash (4.2% vs 1.7%), intestinal obstruction (2.1% vs 0%), and arterial thromboembolic events (1.7% vs 0%).
Across clinical trials of CYRAMZA administered as a single agent, clinically relevant adverse reactions (including grade ≥3) reported in CYRAMZA-treated patients included proteinuria, gastrointestinal perforation, and infusion-related reactions. In study 1, according to laboratory assessment, 8% of CYRAMZA-treated patients developed proteinuria vs 3% of placebo-treated patients. Two patients discontinued CYRAMZA due to proteinuria. The rate of gastrointestinal perforation in study 1 was 0.8% and the rate of infusion-related reactions was 0.4%.
Most Common Adverse Reactions—Combination With Paclitaxel

The most commonly reported adverse reactions (all grades; grade 3/4) occurring in ≥5% of patients receiving CYRAMZA plus paclitaxel and ≥2% higher than placebo plus paclitaxel in study 2 were fatigue/asthenia (57% vs 44%; 12% vs 6%), neutropenia (54% vs 31%; 41% vs 19%), diarrhea (32% vs 23%; 4% vs 2%), epistaxis (31% vs 7%; 0% vs 0%), hypertension (25% vs 6%; 15% vs 3%), peripheral edema (25% vs 14%; 2% vs 1%), stomatitis (20% vs 7%; 1% vs 1%), proteinuria (17% vs 6%; 1% vs 0%), thrombocytopenia (13% vs 6%; 2% vs 2%), hypoalbuminemia (11% vs 5%; 1% vs 1%), and gastrointestinal hemorrhage events (10% vs 6%; 4% vs 2%).
The most common serious adverse events with CYRAMZA plus paclitaxel in study 2 were neutropenia (3.7%) and febrile neutropenia (2.4%); 19% of patients treated with CYRAMZA plus paclitaxel received granulocyte colony-stimulating factors.
Adverse reactions resulting in discontinuation of any component of the CYRAMZA plus paclitaxel combination in 2% or more patients in study 2 were neutropenia (4%) and thrombocytopenia (3%).
Clinically relevant adverse reactions reported in ≥1% and < 5% of the CYRAMZA plus paclitaxel-treated patients in study 2 were sepsis (3.1% for CYRAMZA plus paclitaxel vs 1.8% for placebo plus paclitaxel) and gastrointestinal perforations (1.2% for CYRAMZA plus paclitaxel vs 0.3% for placebo plus paclitaxel).
Most Common Adverse Reactions—Combination With Docetaxel

The most commonly reported adverse reactions (all grades; grade 3/4) occurring in ≥5% of patients receiving CYRAMZA plus docetaxel and ≥2% higher than placebo plus docetaxel in study 3 were neutropenia (55% vs 46%; 49% vs 40%), fatigue/asthenia (55% vs 50%; 14% vs 11%), stomatitis/mucosal inflammation (37% vs 19%; 7% vs 2%), epistaxis (19% vs 7%; < 1% vs < 1%), febrile neutropenia (16% vs 10%; 16% vs 10%), peripheral edema (16% vs 9%; 0% vs < 1%), thrombocytopenia (13% vs 5%; 3% vs < 1%), lacrimation increased (13% vs 5%; < 1% vs 0%), and hypertension (11% vs 5%; 6% vs 2%).
The most common serious adverse events with CYRAMZA plus docetaxel in study 3 were febrile neutropenia (14%), pneumonia (6%), and neutropenia (5%). The use of granulocyte colony-stimulating factors was 42% in CYRAMZA plus docetaxel-treated patients versus 37% in patients who received placebo plus docetaxel.
In patients ≥65 years of age, there were 18 (8%) deaths on treatment or within 30 days of discontinuation for CYRAMZA plus docetaxel and 9 (4%) deaths for placebo plus docetaxel. In patients < 65 years of age, there were 13 (3%) deaths on treatment or within 30 days of discontinuation for CYRAMZA plus docetaxel and 26 (6%) deaths for placebo plus docetaxel.
Treatment discontinuation due to adverse reactions occurred more frequently in CYRAMZA plus docetaxel-treated patients (9%) than in placebo plus docetaxel-treated patients (5%). The most common adverse events leading to treatment discontinuation of CYRAMZA in study 3 were infusion-related reaction (0.5%) and epistaxis (0.3%).
For patients with nonsquamous histology, the overall incidence of pulmonary hemorrhage was 7% and the incidence of grade ≥3 pulmonary hemorrhage was 1% for CYRAMZA plus docetaxel compared to 6% overall incidence and 1% for grade ≥3 pulmonary hemorrhage for placebo plus docetaxel. For patients with squamous histology, the overall incidence of pulmonary hemorrhage was 10% and the incidence of grade ≥3 pulmonary hemorrhage was 2% for CYRAMZA plus docetaxel compared to 12% overall incidence and 2% for grade ≥3 pulmonary hemorrhage for placebo plus docetaxel.
Clinically relevant adverse reactions reported in ≥1% and < 5% of CYRAMZA plus docetaxel-treated patients in study 3 were hyponatremia (4.8% CYRAMZA plus docetaxel versus 2.4% for placebo plus docetaxel) and proteinuria (3.3% CYRAMZA plus docetaxel versus 0.8% placebo plus docetaxel).
Most Common Adverse Reactions—Combination With FOLFIRI

The most commonly reported adverse reactions (all grades; grade 3/4) occurring in ≥5% of patients receiving CYRAMZA plus FOLFIRI and ≥2% higher than placebo plus FOLFIRI in study 4 were diarrhea (60% vs 51%; 11% vs 10%), neutropenia (59% vs 46%; 38% vs 23%), decreased appetite (37% vs 27%; 2% vs 2%), epistaxis (33% vs 15%; 0% vs 0%), stomatitis (31% vs 21%; 4% vs 2%), thrombocytopenia (28% vs 14%; 3% vs < 1%), hypertension (26% vs 9%; 11% vs 3%), peripheral edema (20% vs 9%; < 1% vs 0%), proteinuria (17% vs 5%; 3% vs < 1%), palmar-plantar erythrodysesthesia syndrome (13% vs 5%; 1% vs < 1%), gastrointestinal hemorrhage events (12% vs 7%; 2% vs 1%), hypoalbuminemia (6% vs 2%; 1% vs 0%). Twenty percent of patients treated with CYRAMZA plus FOLFIRI received granulocyte colony-stimulating factors.
The most common serious adverse events with CYRAMZA plus FOLFIRI were diarrhea (3.6%), intestinal obstruction (3.0%), and febrile neutropenia (2.8%).
Treatment discontinuation of any study drug due to adverse reactions occurred more frequently in CYRAMZA plus FOLFIRI-treated patients (29%) than in placebo plus FOLFIRI-treated patients (13%). The most common adverse reactions leading to discontinuation of any component of CYRAMZA plus FOLFIRI as compared to placebo plus FOLFIRI were neutropenia (12.5% versus 5.3%) and thrombocytopenia (4.2% versus 0.8%). The most common adverse reactions leading to treatment discontinuation of CYRAMZA were proteinuria (1.5%) and gastrointestinal perforation (1.7%).
Clinically relevant adverse reactions reported in ≥1% and < 5% of CYRAMZA plus FOLFIRI-treated patients in study 4 consisted of gastrointestinal perforation (1.7% CYRAMZA plus FOLFIRI versus 0.6% for placebo plus FOLFIRI).
Thyroid-stimulating hormone (TSH) was evaluated in 224 patients (115 CYRAMZA plus FOLFIRI-treated patients and 109 placebo plus FOLFIRI-treated patients) with normal baseline TSH levels. Increased TSH was observed in 53 (46%) patients treated with CYRAMZA plus FOLFIRI compared with 4 (4%) patients treated with placebo plus FOLFIRI.
Drug Interactions

No pharmacokinetic interactions were observed between ramucirumab and paclitaxel, between ramucirumab and docetaxel, or between ramucirumab and irinotecan or its active metabolite, SN-38.
Use in Specific Populations

Pregnancy: Based on its mechanism of action, CYRAMZA can cause fetal harm. Animal models link angiogenesis, VEGF, and VEGF Receptor 2 (VEGFR2) to critical aspects of female reproduction, embryofetal development, and postnatal development. There are no available data on CYRAMZA use in pregnant women to inform any drug-associated risks. No animal studies have been conducted to evaluate the effect of ramucirumab on reproduction and fetal development. Advise females of reproductive potential of the potential risk for maintaining pregnancy, risk to the fetus, and risk to newborn and pediatric development, and to use effective contraception during CYRAMZA therapy and for at least 3 months following the last dose of CYRAMZA.
Lactation: Because of the potential risk for serious adverse reactions in nursing infants from ramucirumab, advise women that breastfeeding is not recommended during treatment with CYRAMZA.
Females of Reproductive Potential: Advise females of reproductive potential that based on animal data CYRAMZA may impair fertility.
Please see full Prescribing Information for CYRAMZA, including Boxed Warning for hemorrhage, gastrointestinal perforation, and impaired wound healing.

RB-P-HCP ISI 16FEB2017

About Lilly Oncology
For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. To learn more about Lilly’s commitment to people with cancer, please visit www.LillyOncology.com.

On December 8, 2017 Adaptive Biotechnologies, the leader in using next-generation sequencing (NGS) to detect minimal/measurable residual disease (MRD) in blood cancers, and its collaborators reported that they will present 22 studies, including a late-breaker presentation, at the 59th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Atlanta, December 9-12 (Press release, , DEC 8, 2017, View Source [SID1234522517]). Data presented at ASH (Free ASH Whitepaper) will demonstrate how Adaptive’s clonoSEQ Assay to measure MRD, the cancerous cells remaining in the body after treatment, can inform clinical care in patients with B and T cell lymphoid malignancies. Additionally, at ASH (Free ASH Whitepaper), Adaptive and its collaborators will present data from studies utilizing the company’s research-based immunosequencing platform, immunoSEQ, to identify potential biomarkers of response to therapy.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"MRD is increasingly viewed as a critical endpoint in lymphoid cancers used to assess a patient’s response to cancer treatment and evaluate disease burden over time. At Adaptive, we are excited to see the growing use of this endpoint to support clinical trials and patient management," said Charles Sang, Senior Vice President of Diagnostics. "We leveraged our foundational immunosequencing platform to develop the clonoSEQ Assay which provides a highly sensitive and standardized determination of residual disease in patients with lymphoid malignancies."

clonoSEQ, the first clinical application of Adaptive’s pioneering immunosequencing platform, is helping to set a new standard for assessment of minimal residual disease in the clinic. It will be featured in a late breaker presentation, 5 orals and 7 posters. Data will be presented across a range of cancers – 9 multiple myeloma, 1 peripheral T-cell lymphoma, 1 mantle cell lymphoma, 1 chronic lymphocytic leukemia, 1 follicular lymphoma. Abstracts of importance include:

LBA-4 Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE) (LBA-4)
Minimal Residual Disease in Multiple Myeloma: Final Analysis of the IFM2009 Trial (Abstract #435)
Daratumumab, Lenalidomide, and Dexamethasone (DRd) Versus Lenalidomide and Dexamethasone (Rd) in Relapsed or Refractory Multiple Myeloma (RRMM): Updated Efficacy and Safety Analysis of Pollux (Abstract #739)
Below is a full list of clonoSEQ and immunoSEQ related abstracts that will be presented at ASH (Free ASH Whitepaper) this year.

CLONOSEQ ORAL ABSTRACT AND POSTER PRESENTATION HIGHLIGHTS:

Saturday, December 9, 2017

Oral Presentation, Abstract #154 Initial Treatment with Lenalidomide Plus Rituximab for Mantle Cell Lymphoma: 5-Year Follow-up and Correlative Analysis from a Multi-Center Phase II Study

Presenter: Jia Ruan, MD, PhD, Weill Cornell Medicine and New York Presbyterian Hospital, New York, NY

Time: 12:45 – 1:00 PM

Location: Bldg A, Lvl 4, A411-A412 (Georgia World Congress Center)

Poster Presentation, Abstract #1824 Daratumumab in Combination with Pomalidomide and Dexamethasone for RRMM Patients with ≥2 Prior Lines of Therapy: Updated Analysis of MMY1001

Presenter: Thierry Facon, Department of Haematology, Lille University Hospital, Lille, France

Time: 5:30 – 7:30 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Poster Presentation, Abstract #1852 Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone for Relapsed/Refractory Multiple Myeloma (RRMM) Patients: An Update of Overall Survival in Castor

Presenter: Suzanne Lentzsch, Columbia University Medical Center, New York, NY

Time: 5:30 – 7:30 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Poster Presentation, Abstract #1883 Daratumumab, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in RRMM Based on Prior Treatment History, Renal Function, and Cytogenetic Risk: Subgroup Analyses of Pollux

Presenter: Philippe Moreau, Hematology, University Hospital Hôtel-Dieu, Nantes, France

Time: 5:30 – 7:30 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Sunday, December 10, 2017

Oral Presentation, Abstract #435 Minimal Residual Disease in Multiple Myeloma: Final Analysis of the IFM2009 Trial

Presenter: Hervé Avet-Loiseau, MD, PhD, UC-Oncopole, Unite de Genomique du Myelome, Toulouse, France

Time: 12:30 – 12:45 PM

Location: Bldg C, Lvl 1, Hall C4 (Georgia World Congress Center)

Oral Presentation, Abstract #496 A Multicenter, Phase II Study of Ibrutinib Plus FCR As Frontline Therapy for Younger CLL Patients

Presenter: Matthew S. Davids, MD, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

Time: 5:15 – 5:30 PM

Location: Bldg B, Lvl 5, Murphy BR 3-4 (Georgia World Congress Center)

Poster Presentation, Abstract #2728 Next-Generation Sequencing Based Monitoring of Circulating-Tumor DNA in Untreated Peripheral T-Cell Lymphoma

Presenter: Christopher Melani, MD, Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Baltimore, MD

Time: 6:00 – 8:00 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Poster Presentation, Abstract #3145 Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in RRMM: Updated Efficacy and Safety Analysis of Castor

Presenter: Andrew Spencer, MD, Malignant Haematology and Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne, Australia

Time: 6:00 – 8:00 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Monday, December 11, 2017

Oral Presentation, Abstract #739 Daratumumab, Lenalidomide, and Dexamethasone (DRd) Versus Lenalidomide and Dexamethasone (Rd) in Relapsed or Refractory Multiple Myeloma (RRMM): Updated Efficacy and Safety Analysis of Pollux

Presenter: Meletios A. Dimopoulos, National and Kapodistrian University of Athens, Athens, Greece

Time: 2:45 – 3:00 PM

Location: Bldg C, Lvl 1, Hall C1 (Georgia World Congress Center)

Poster Presentation, Abstract #4533 High Rate of Sustained Minimal Residual Disease Negativity Predicts Prolonged Survival for the Overall Patient Population in the Phase 2 KRd Plus Autologous Stem Cell Transplantation MMRC Trial

Presenter: Andrzej J. Jakubowiak, MD, University of Chicago Medical Center, Chicago, IL

Time: 6:00 – 8:00 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Poster Presentation, Abstract #4685 Measurable Residual Disease (MRD) Testing in Multiple Myeloma Using an Improved Testing Technology: Population Impact

Presenter: Marita Zimmermann, PhD, MPH, Veritech Corporation, Seattle, WA

Time: 6:00 – 8:00 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Tuesday, December 12, 2017

Late Breaker Presentation: LBA-4 Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible for Transplant (ALCYONE)

Presenter: Maria-Victoria Mateos, University Hospital of Salamanca/IBSAL, Salamanca, Spain

Time: 7:30 AM-9:00 AM

Location: Bldg C, Lvl 1, Hall C2-C3 (Georgia World Congress Center)

IMMUNOSEQ ABSTRACT AND POSTER PRESENTATION HIGHLIGHTS:

Saturday, December 9, 2017

Poster Presentation, Abstract #1898 Quantifying the Size and Diversity of the Human Alloresponse Via High-Throughput T Cell Receptor Sequencing

Presenter: Susan DeWolf, MD, Columbia Center for Translational Immunology (CCTI), Columbia University Medical Center, New York, NY

Time: 5:30 – 7:30 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Poster Presentation, Abstract #2069 Novel Human Anti-HLA-Bw4 and B61 Monoclonal Antibodies Kill Malignant B Cells Via CDC/ADCC While Sparing Normal Peripheral Blood Cells

Presenter: Hiroyuki Takamatsu, MD, PhD, Department of Hematology, Kanazawa University, Kanazawa, Japan

Time: 5:30 – 7:30 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Sunday, December 10, 2017

Poster Presentation, Abstract #2454 Surveillance of the Immune Repertoire of Aplastic Anemia Patients Using Deep Sequencing

Presenter: Cassandra Hirsch, BS, Department of Translational Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH

Time: 6:00 – 8:00 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Poster Presentation, Abstract #2734 Longitudinal Analyses of the Genomic, Transcriptomic, and T-Cell Repertoire in Diffuse Large B-Cell Lymphoma Demonstrates Changes in Signaling and Immune Recognition at Relapse

Presenter: Shamzah Araf, MRCP, MBBS, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom

Time: 6:00 – 8:00 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Poster Presentation, Abstract #2771 Intratumoral G100 Induces Systemic Immunity and Abscopal Tumor Regression in Patients with Follicular Lymphoma: Results of a Phase 1/ 2 Study Examining G100 Alone and in Combination with Pembrolizumab

Presenter: Christopher Flowers, MD, MS, Winship Cancer Institute Bone Marrow & Stem Cell Transplantation, Atlanta, GA

Time: 6:00 – 8:00 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Monday, December 11, 2017

Oral Presentation, Abstract #649 Results from a Phase 1/2 Study of Brentuximab Vedotin in Combination with Nivolumab in Patients with Relapsed or Refractory Hodgkin Lymphoma

Presenter: Alex F. Herrera, MD, City of Hope, Duarte, CA

Time: 10:30 – 10:45 AM

Location: Bldg A, Lvl 4, Marcus Aud. (Georgia World Congress Center)

Oral Presentation, Abstract #728 The Tumor Microenvironment Is Independently Prognostic of Conventional and Clinicogenetic Risk Models in Follicular Lymphoma

Presenter: Joshua W.D. Tobin, University of Queensland, Australia

Time: 3:00 – 3:15 PM

Location: Bldg C, Lvl1, C101 Auditorium (Georgia World Congress Center)

Oral Presentation, Abstract #825 The T-Cell Receptor Repertoire Predicts Interim-PET in Patients with DLBCL Treated with R-CHOP: An Observational Study from a Prospective Clinical Trial

Presenter: Mohamed Shanavas, MD, University of Queensland Diamantina Institute, Brisbane, Australia

Time: 5:00 PM

Location: Bldg C, Lvl 3, Georgia BR 1-3 (Georgia World Congress Center)

Poster Presentation, Abstract # 4506 Day 90 Post-Allogeneic Hematopoietic Cell Transplantation T Cell Receptor Diversity Level Correlates with Risk of Relapse in Patients with Multiple Myeloma

Presenter: Robert Korngold, PhD, John Theurer Cancer Center, Hackensack Univ. Med. Ctr. Jurist Research Bldg., Hackensack, NJ

Time: 6:00 – 8:00 PM

Location: Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

About Minimal/Measurable Residual Disease

Minimal/measurable residual disease (MRD) in hematologic malignancies refers to cancer cells that remain in the body of a person with cancer after treatment. In the case of clonoSEQ this includes ALL and MM. These cells can be present at levels undetectable by traditional morphologic, microscopic examination of blood, bone marrow or a lymph node biopsy. Sensitive molecular technologies, such as next-generation sequencing utilized by the Adaptive Biotechnologies clonoSEQ Assay, may be employed to facilitate the reliable detection of MRD at levels below the limits of traditional assessment.

About the clonoSEQ Assay

The Adaptive Biotechnologies clonoSEQ Assay enables physicians to utilize a molecular, next-generation sequencing-based minimal/measurable residual disease (MRD) detection method. The clonoSEQ Assay detects and quantifies DNA sequences found in malignant cells which can be tracked throughout treatment. This robust assay provides consistent, accurate measurement of disease burden which potentially allows physicians to visualize response to treatment over time. The clonoSEQ assay is not approved or cleared by the FDA and is currently available in a CLIA-certified laboratory. clonoSEQ test results should only be used taking into account all available clinical information and should not be used as the sole determinant of patient care and management.

About the immunoSEQ Platform

Adaptive’s immunoSEQ Platform helps researchers make discoveries in areas such as oncology, autoimmune disorders, infectious diseases and basic immunology. The immunoSEQ Assays can identify millions of T- and B-cell receptors from a single sample in exquisite detail. Offered as a Service or Kit, immunoSEQ Assays provide quantitative, reproducible sequencing results along with access to powerful, easy-to-use analysis tools. The immunoSEQ Assays are for research use only and are not for use in diagnostic procedures.

On December 8, 2017 Rigel Pharmaceuticals, Inc. (Nasdaq:RIGL) reported that the one-year efficacy and safety results from its FIT Phase 3 clinical program of fostamatinib for chronic or persistent immune thrombocytopenia (ITP) will be featured in an oral presentation at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in Atlanta, GA from December 9 to December 12, 2017 (Press release, Rigel, DEC 8, 2017, View Source;p=RssLanding&cat=news&id=2321827 [SID1234522471]).

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During the presentation, James B. Bussel, M.D., professor emeritus of pediatrics at Weill Cornell Medicine and the principal study investigator on the FIT Phase 3 program who has served as a member of an advisory/scientific board for Rigel Pharmaceuticals, will share an overview of the FIT clinical program.

Oral Presentation Details:
TITLE: Long-Term Maintenance of Platelet Responses in Adult Patients with Persistent/Chronic Immune Thrombocytopenia Treated with Fostamatinib: 1-Year Efficacy and Safety Results
Session Name: 311. Disorders of Platelet Number or Function: ITP: clinical aspects
Session Date: Saturday, December 9, 2017
Session Time: 7:30 AM – 9:00 AM EST
Presentation Time: 8:15 AM EST
Location: Georgia World Congress Center, Bldg B, Lvl 3, B304-B305 (Atlanta, GA)

About Fostamatinib in ITP
Fostamatinib, an oral spleen tyrosine kinase (SYK) inhibitor, is an investigational drug for adult patients with chronic or persistent immune thrombocytopenia (ITP). The New Drug Application (NDA) for fostamatinib for adult patients with chronic or persistent ITP, which was previously granted Orphan Drug designation, is currently under review by the U.S. Food and Drug Administration with a Prescription Drug User Fee Act (PDUFA) goal date of April 17, 2018. The conditionally approved proprietary name for fostamatinib (as confirmed by the FDA) is TAVALISSETM.

The NDA is supported by data from the FIT Phase 3 clinical program, which was comprised of three studies, two randomized placebo-controlled studies (Studies 047 and 048) and an open-label extension study (Study 049). Together with an initial proof of concept study, the NDA included 163 ITP patients. Across all indications, fostamatinib has been evaluated in over 4,600 subjects. Data from all studies, including preclinical evaluation and drug manufacturing data, were included in the NDA submission.

About ITP
In patients with ITP, the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with increased risk of severe bleeding events that can result in serious medical complication, or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPOs) and splenectomy. However, not all patients are adequately treated with existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

On December 7, 2017 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that updated safety and efficacy data from two subgroups of patients with metastatic breast cancer from an ongoing phase 1 study of DS-8201, an investigational HER2-targeting antibody drug conjugate (ADC), were presented during a Spotlight Poster Discussion session at the 2017 San Antonio Breast Cancer Symposium (Press release, Daiichi Sankyo, DEC 7, 2017, View Source [SID1234522441]).

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Updated preliminary results in a subgroup analysis of 57 efficacy evaluable patients with HER2-positive metastatic breast cancer pre-treated with ado-trastuzumab emtansine (T-DM1) showed that DS-8201 demonstrated a confirmed overall response rate of 61.4 percent (35 of 57 patients) and a disease control rate of 94.7 percent (54 of 57 patients). Among 50 of these patients who also were pre-treated with pertuzumab, DS-8201 demonstrated a confirmed overall response rate of 62 percent (31 of 50 patients) and a disease control rate of 94 percent (47 of 50 patients). In 39 efficacy evaluable HER2-positive patients with hormone-receptor positive disease, DS-8201 demonstrated an overall response rate of 56.4 percent (22 of 39 patients) and disease control rate of 92.3 percent (36 of 39 patients). The majority of patients with HER2-positive metastatic breast cancer were continuing to receive treatment at the time of data cut-off. Preliminary estimates of median progression free survival have reached 10.4 months.

Additionally, preliminary results in another subgroup showed that DS-8201 demonstrated a confirmed overall response rate of 31.6 percent (6 of 19 patients) and a disease control rate of 84.2 percent (16 of 19 patients) in 19 efficacy evaluable patients with heavily pretreated HER2 low-expressing breast cancer (defined as IHC2+/ISH- or IHC 1+). In 16 of these patients also classified with hormone-receptor positive disease, DS-8201 demonstrated an overall response rate of 31.3 percent (5 of 16 patients) and a disease control rate of 87.5 percent (14 of 16 patients). Most patients with HER2 low-expressing breast cancer were continuing to receive treatment at the time of data cut-off. Median progression free survival has not yet been reached.

"These updated data in HER2-positive metastatic breast cancer are exciting in that DS-8201 is showing potential in treating patients who have progressed on several other HER2-targeting agents," said Shanu Modi, MD, Breast Medical Oncologist, Memorial Sloan Kettering Cancer Center and study investigator. "Additionally, the results seen in patients with HER2 low-expressing breast cancer are compelling and could challenge how we define HER2-positive breast cancer with regards to ADC therapy. Clearly, further study of DS-8201 is warranted in both these types of HER2-expressing breast cancer."

"These data add to the growing evidence that underscore the potential of our smart chemotherapy DS-8201 to treat HER2-expressing breast cancer," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "While we already have advanced DS-8201 into a pivotal phase 2 trial for HER2-positive metastatic breast cancer, we are exploring next steps for the development of DS-8201 in HER2 low-expressing breast cancer."

Combined preliminary safety data for both HER2 low-expressing and HER2-positive breast cancer subgroups were reported. The most common adverse events (>30 percent any grade) included nausea (73.0 percent), decreased appetite (55.7 percent), alopecia (40.0 percent), vomiting (39.1 percent), anemia (34.8 percent), diarrhea (33.9 percent) and constipation (30.4 percent). Grade 3 adverse events occurring in >10 percent of patients included decreased neutrophil count (10.4 percent) and decreased white blood cell count (10.4 percent). Grade 4 adverse events included decreased neutrophil count (4.3 percent), decreased platelet count (2.6 percent) and anemia (0.9 percent). Two cases of potential Grade 5 pneumonitis have been reported and will be assessed by an interstitial lung disease (ILD) adjudication committee.

Unmet Need in HER2-Expressing Metastatic Breast Cancer
About one in five breast cancers overexpress HER2, a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells, which is associated with aggressive disease.1 To be considered HER2-positive, tumor cancer cells are usually tested by one of two methods: immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH).1 IHC test results are reported as: 0, IHC1+, IHC2+ or IHC3+.1 A finding of IHC3+ is considered HER2-positive.1 A finding of IHC2+ is borderline and typically is confirmed by a positive FISH test.1

Several unmet needs remain today in HER2-expressing metastatic breast cancer. Many tumors advance to the point where no currently approved HER2-targeting treatment continues to control the disease, and there is no current standard of care for HER2-positive tumors after treatment with trastuzumab, pertuzumab and T-DM1.2 Additionally, there are no anti-HER2 therapies indicated for HER2 low-expressing tumors (IHC2+/FISH- or IHC1+).

About the DS-8201 Phase 1 Study
The open-label, two-part phase 1 study is currently evaluating DS-8201 in patients with advanced/
unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation phase of the study was to assess the safety and tolerability of DS-8201 and determine the maximum tolerated dose. In the dose expansion part of the phase 1 study, DS-8201 is given in one of two doses (5.4 mg/kg and 6.4 mg/kg) to patients with HER2-positive advanced or metastatic breast cancer and gastric cancer, HER2 low-expressing breast cancer and other HER2-expressing solid tumors. Patient enrollment in the two breast cancer cohorts and the HER2-expressing solid tumors cohort is ongoing in the U.S. and Japan. For more information about the study, please visit ClinicalTrials.gov.

About DS-8201
DS-8201 is the lead product in the ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, DS-8201 is a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-8201 is currently in phase 2 clinical development for HER2-positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01), phase 2 development for HER2-positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01), and phase 1 development for other HER2-expressing advanced/unresectable or metastatic solid tumors.

DS-8201 has been granted Breakthrough Therapy designation for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). DS-8201 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise
The vision of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking in order to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by our Antibody Drug Conjugate (ADC) and Acute Myeloid Leukemia (AML) Franchises, our cancer pipeline includes more than 20 small molecules, monoclonal antibodies and ADCs stemming from our powerful research engines: our two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in development include: quizartinib, an oral FLT3 inhibitor, for newly-diagnosed and relapsed or refractory AML with FLT3-ITD mutations; DS-8201, an ADC for HER2-expressing breast and gastric cancer, and other HER2-expressing solid tumors; and pexidartinib, an oral CSF-1R inhibitor, for tenosynovial giant cell tumor (TGCT), which is also being explored in a range of solid tumors in combination with the anti-PD1 immunotherapy pembrolizumab. For more information, please visit: www.DSCancerEnterprise.com.

On December 7, 2017 Northwest Biotherapeutics (OTCQB: NWBO) (NWBio), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported that it has completed a $12 million financing to fund operations (Press release, Northwest Biotherapeutics, DEC 7, 2017, View Source [SID1234522446]). The majority of the financing is being provided by new investors.

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The financing is in the form of Series A Convertible Preferred Stock and Warrants. The Preferred Stock will be convertible into common stock, but only when common stock is available or after 6 months following issuance. The Warrants will be exercisable for common stock, but only when common stock is available. The shares are registered, but are subject to restrictions under which they may not be conveyed or traded until a shareholder vote takes place, pursuant to which the number of authorized shares is increased. The shares are also subject to a voting agreement, under which the investors have agreed to vote in support of such increase in authorized shares.

The investors are purchasing the Series A Preferred Stock at a price of $1.70 per share, and each such preferred share will be convertible into 10 common shares valued at $0.17 cents per share. The investors are also receiving Warrants for a number of common shares equal to the number of conversion shares, with an exercise price of $0.22 per share and an exercise period of two years.

As reported in the Company’s recent 10-Q filing, the Company has been in discussions with investors for this financing during the last couple of months. During this period, while the price of the Company’s common stock hovered mostly at $0.16- $0.17 per share, the terms were set at $0.17 per share of common stock and $0.22 exercise price for the warrants. As also previously reported, some of the investors provided advance funding prior to completion of the financing and its documentation.

Linda Powers, the Company’s CEO, commented, "We are pleased to see a growing number of new investors becoming interested in our DCVax technology and its encouraging potential, and providing the majority of the largest financing we have done this year. We are also grateful for our long-term, patient and loyal shareholder base, and their participation in this financing as well. It is gratifying to have both ongoing and expanded support as we move forward with our ongoing Phase 3 trial (in which we are continuing to ship doses, treat patients and collect data) and other programs we have been preparing."