On November 13, 2017 Celsion Corporation (NASDAQ:CLSN), an oncology drug development company, reported the submission of its Phase I/II clinical trial protocol to the U.S. Food and Drug Administration (FDA) for GEN-1, the Company’s DNA-based immunotherapy for the localized treatment of ovarian cancer (Press release, Celsion, NOV 13, 2017, View Source [SID1234521999]). The protocol, developed in conjunction with guidance from the Company’s Medical Advisory Board, is designed with a single dose escalation to evaluate the safety and biological activity of GEN-1 at 100mg/m² in newly diagnosed Stage III/IV ovarian cancer patients, followed by a continuation at the selected dose in Phase II in a 90 patient 1 to 1 randomized study. GEN-1 has demonstrated encouraging safety and efficacy data in a recently completed dose escalating Phase IB trial in combination with neoadjuvant chemotherapy, the standard of care for patients newly diagnosed with ovarian cancer. Concurrently with neoadjuvant chemotherapy, enrolled patients received escalating weekly doses of GEN-1, from levels beginning at 36mg/m², to 47mg/m², 61mg/m² and 79mg/m² weekly for 8 treatments in total, followed by interval debulking surgery.

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"GEN-1 is designed to locally activate IL-12 production which can recruit and stimulate the patient’s immune system to attack and destroy cancer," stated Dr. Nicolas Borys, Celsion’s senior vice president and chief medical officer. "In preclinical and multiple Phase I clinical studies performed to date, GEN-1 has demonstrated good safety and impressive immune system stimulation and clinical activity. This trial will evaluate its value as an adjuvant to current standard of care in newly diagnosed Stage III/IV ovarian cancer patients with a relatively healthy immune system. We look forward to initiating the study in the first half of 2018."
The Phase I/II study builds on the highly promising clinical and translational research data for the recently completed Phase IB dose-escalating OVATION Study. This next Phase I/II study will have a dose escalating phase to 100 mg/m² to identify a safe and tolerable dose of GEN-1 while maximizing an immune response. The study protocol was unanimously supported by an expert medical advisory board and lead investigators from the Phase IB OVATION Study and is summarized below:

Open label, 1:1 randomized design

Enrollment up to 90 patients with Stage III/IV ovarian cancer patients at ten U.S. centers
Primary endpoint of improvement in progression-free survival (PFS) comparing GEN-1 with neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone.

PFS for patients treated per protocol in the Phase IB OVATION Study continues to be followed. Of the eight patients who received GEN-1 treatment over one year ago (cohort 1 – 3) and are being followed, only three patients’ cancer has progressed. This compares favorably to the historical median progression-free survival of 12 months for newly-diagnosed patients with Stage III and IV ovarian cancer that undergo neoadjuvant chemotherapy followed by interval debulking surgery. Of the remaining five patients who have been on the OVATION Study for over one year, their median PFS as of October 31, 2017 is 18.8 months with the longest progression-free patient at 24 months.

The protocol has been submitted to the FDA for its 30 day review and comment period. Pending this review, the Company expects to initiate enrollment of the Phase I portion of the study in the first half of 2018. The Company expects to have the study 50% enrolled by the end of 2018. Due to the open label design, clinical data will be disclosed throughout the execution of the trial as it is released by the study’s investigators.

"GEN-1 holds the potential of tremendous promise as a cancer treatment in the rapidly emerging area of immuno-oncology. Unlike the toxicities, poor tolerability, and poor pharmacokinetics of systemically administered recombinant IL-12, the beauty of GEN-1 is that it inspires secretion of highly-tolerable endogenous IL-12," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "Designed in consultation with leading thought leaders, this Phase I/II trial is expected to define an optimal dose, demonstrate GEN-1’s clinical benefit when compared with current standard of care, and provide insights on powering for a registration program as the candidate progresses through development."

About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy in patients with peritoneally metastasized ovarian cancer, and recently completed a Phase Ib trial of GEN-1 in combination with PEGylated doxorubicin in patients with platinum-resistant ovarian cancer.

On November 13, 2017 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly targeted and immuno-oncology drugs for the treatment of cancer, reported the initiation of two new global pivotal clinical trials of BGB-3111, an investigational Bruton’s Tyrosine Kinase (BTK) inhibitor, including a Phase 3 trial of BGB-3111 in previously untreated patients with CLL/SLL and a pivotal Phase 2 trial of BGB-3111 in combination with GAZYVA (obinutuzumab) in patients with relapsed or refractory FL (Press release, BeiGene, NOV 13, 2017, View Source;p=RssLanding&cat=news&id=2316623 [SID1234521996]). Along with a global Phase 3 trial comparing BGB-3111 to ibrutinib in Waldenström’s macroglobulinemia (WM), initiated in early 2017, BGB-3111 is now being evaluated in global pivotal trials in three distinct indications. Additionally, BGB-3111 is being evaluated in a broad pivotal clinical development program in China, including ongoing pivotal Phase 2 trials in MCL, CLL, and WM, which was initiated in August 2017. BeiGene also announced today that enrollment in the pivotal Phase 2 trial of BGB-3111 in China in MCL patients was completed in September 2017.

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"The initiation of two additional pivotal trials expands our global registration-directed clinical development of BGB-3111 to additional indications, including patients with follicular lymphoma, a common B cell malignancy for which BTK inhibitors are not yet approved. We look forward to continuing the development of BGB-3111 as a potentially best-in-class BTK inhibitor for patients worldwide who suffer from hematological malignancies," commented John V. Oyler, Founder, Chief Executive Officer, and Chairman of BeiGene.

"We believe that these two new pivotal trials are supported by our growing clinical experience with BGB-3111, in which over 600 patients have been dosed to date. With the newly initiated Phase 3 CLL/SLL trial, we aim to investigate whether BGB-3111 could be an effective treatment option for a broad population of CLL/SLL patients requiring initial treatment. The initiation of the pivotal trial in follicular lymphoma is an effort to determine whether the combination of BGB-3111 and obinutuzumab represents an effective treatment option for a high-unmet-need population of relapsed or refractory patients to potentially support the pursuit of accelerated or conditional approval of this regimen," commented Jane Huang, M.D., Chief Medical Officer, Hematology.

Trial Design

The Phase 3 trial in CLL/SLL is designed to compare BGB-3111 to BR and will be conducted in North America, Europe, Australia, New Zealand, and Asia. The study will enroll previously untreated CLL/SLL patients ineligible for intensive chemo-immunotherapy (i.e., fludarabine, cyclophosphamide, and rituximab), who will be divided into two cohorts. The first cohort is designed to include 420 patients without a 17p deletion (del17p), who will be randomized in a 1:1 ratio to receive either BGB-3111 until progression or six cycles of BR. Crossover will be allowed in the BR arm upon progression. The primary endpoint will be progression-free survival (PFS), and secondary endpoints include overall response rate (ORR), duration of response (DOR), overall survival (OS), and patient-reported outcomes. Patients with del17p will be enrolled in a second cohort to receive BGB-3111 until progression and will be assessed for response and safety.

The pivotal Phase 2 trial in FL is designed to evaluate BGB-3111 in combination with obinutuzumab in patients who have had at least two prior lines of therapy and who progressed within 12 months of their last treatment or were refractory to their last treatment. The primary endpoint will be ORR and obinutuzumab monotherapy will be included as a comparator, in order to evaluate the contribution of BGB-3111. The trial is expected to enroll approximately 210 patients in North America, Europe, Australia, and New Zealand who will be randomized 2:1 to receive either BGB-3111 with obinutuzumab or obinutuzumab alone. Patients in the obinutuzumab arm will have the option to add BGB-3111 after 12 months if a response has not been achieved. Secondary endpoints of the study include DOR, PFS, OS, and time to response.

About BGB-3111

BGB-3111 is a potent and highly selective investigational small molecule inhibitor of BTK. BGB-3111 has demonstrated higher selectivity against BTK than ibrutinib, a BTK inhibitor currently approved by the U.S. Food and Drug Administration and the European Medicines Agency, based on biochemical assays, higher exposure than ibrutinib based on their respective Phase 1 experience in separate trials, and sustained 24-hour BTK occupancy in both the peripheral blood and lymph node compartments.

On November 13, 2017 Arcus Biosciences, a clinical-stage biotechnology company focused on the discovery and development of innovative cancer immunotherapies, reported the completion of a $107 million Series C financing (Press release, Arcus Biosciences, NOV 13, 2017, View Source [SID1234521995]). This financing brings the total equity capital that the company has raised since its inception in 2015 to $227 million.

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The proceeds from this financing will be used for the advancement of Arcus’s clinical programs for AB928, a first-in-class dual adenosine receptor antagonist, and AB122, a PD-1 antibody. Earlier this month, Arcus initiated a phase 1 trial of AB928 in healthy volunteers and Arcus plans to initiate a phase 1/2 trial of AB928 in combination with AB122 in cancer patients during the first half of 2018. Also in November, Arcus initiated a phase 1 trial of AB122 in cancer patients in Australia. Data from the AB122 trial will be available in 2018 and Arcus plans to evaluate AB122 in combination with its other product candidates, in addition to AB928, in the future. The proceeds raised will also allow Arcus to advance at least two additional product candidates into clinical development, including AB680, a first-in-class small molecule CD73 inhibitor, and AB154, a TIGIT antibody.

The financing was led by GV (formerly Google Ventures), with participation from new investors, including Wellington Management Company LLP, EcoR1 Capital, BVF Partners L.P., Decheng Capital, Hillhouse, Aisling Capital and entities affiliated with Leerink Partners. Arcus’s existing investors, including The Column Group, Foresite Capital, Invus Opportunities, DROIA, Celgene Corporation and Taiho Ventures, also participated in the financing.

"We are extremely pleased to add several outstanding investors with significant expertise in biotechnology to our investor group," said Terry Rosen, Ph.D., CEO of Arcus Biosciences. "We have been assembling a team of staff, investors, leadership and advisors with a highly aligned long-term vision to create, develop and commercialize innovative cancer immunotherapies that may offer a meaningful benefit to patients over existing treatments. These new investors share this vision, and we are thrilled to add their expertise, leadership and commitment to our team."

On November 13, 2017 Array BioPharma Inc. (Nasdaq: ARRY), a biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule cancer therapies, reported data from the Phase 1b clinical trial evaluating the immunotherapy combination of ARRY-382, with Merck’s KEYTRUDA (pembrolizumab), an anti-PD-1 antibody, in patients with certain advanced solid tumors, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 32nd Annual Meeting, being held Nov. 8-12, 2017 in National Harbor, Maryland (Press release, Array BioPharma, NOV 13, 2017, View Source;p=RssLanding&cat=news&id=2316453 [SID1234521957]). ARRY-382 is a highly selective oral inhibitor of the CSF1R kinase and would be among the first investigational compounds targeting this pathway.

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"We are pleased to announce completion of the Phase 1b clinical study of ARRY-382 in combination with KEYTRUDA. In addition to establishing an appropriate Phase 2 dose for the combination, we are encouraged by the early signs of activity in patients with tumor types that have been historically unresponsive to anti-PD1 therapies," said Ron Squarer, Chief Executive Officer, Array BioPharma.

In the Phase 1b dose escalation trial, the recommended Phase 2 dose of ARRY-382 was determined to be 300 mg daily in combination with KEYTRUDA 2 mg/kg given intravenously every 3 weeks.

Nineteen patients, with a median of two prior lines of therapy and 42% with ≥3 prior regimens, were treated in the study. Patients with pancreatic (n=6), colorectal (n=5), ovarian (n=3), gastric and melanoma (n=2, each), and triple negative breast cancer (n=1) were enrolled. Investigators noted that ARRY-382 had a manageable safety profile when administered with KEYTRUDA in this study, and the most common grade 3/4 adverse events (AEs) (>10%), regardless of causality, included increased AST, increased blood creatine kinase (CK), rash, increased lipase, increased alkaline phosphatase (ALP), increased alanine aminotransferase (ALT) and anemia.

The combination of ARRY-382 and KEYTRUDA demonstrated early signs of activity, with 11% (n=2) of patients achieving a confirmed partial response, based on RECIST version 1.1 guidelines The first responder, who was treated with ARRY-382 at 200 mg, had Stage III pancreatic ductal adenocarcinoma. As of the data cut-off, this patient was on study treatment in cycle 14 (42 weeks). The second responder, who was treated with ARRY-382 at 300 mg, had stage IV ovarian cancer with liver metastasis. As of the data cut-off, this patient was on study treatment in cycle 8 (24 weeks).

The current trial was designed to enroll Phase 2 cohorts in both melanoma and non-small cell lung cancer patients, and now Array plans to expand the study to include other patient populations, including a cohort of pancreatic cancer patients. The Phase 2 portion of the study is currently active and enrolling patients.

About CSF1R and ARRY-382

Colony-stimulating factor 1 receptor (CSF1R) is a cell-surface receptor for its ligands, colony-stimulating factor 1 (CSF1) and IL-34.[1, 2] CSF1R is thought to play an important role as regulator of the development, morphology, survival, and functions of tissue macrophages as well as tumor-associated macrophages (TAMs). TAMs play a role in modulating anti-tumor adaptive immunity and CSF1 is believed to be a driver of TAM differentiation towards an immunosuppressive tumor promoting phenotype. Increased CSF1 expression is implicated in tumor progression and metastasis, and is associated with poor prognosis in some cancers.[3] Combining a PD-1 inhibitor with a CSF1R inhibitor in preclinical models shows enhanced antitumor activity. ARRY-382 is a highly selective, oral inhibitor of CSF1R.

On November 14, 2017 Novartis reported that it will present data across its breast cancer portfolio and pipeline in a broad range of patient populations, treatment combinations and pathways at the upcoming 40th annual San Antonio Breast Cancer Symposium (SABCS), San Antonio, December 5-9 (Press release, Novartis, NOV 13, 2017, View Source [SID1234522029]).

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"Our presentations at SABCS will address some of the most pressing challenges and questions facing the advanced breast cancer community, including the need to better understand treatment sequencing and biomarkers," said Bruno Strigini, CEO, Novartis Oncology. "At Novartis, we seek to advance scientific understanding of breast cancer with the ultimate goal of improving treatments and outcomes for those affected by the disease. We are pleased to share the latest data from our MONALEESA program, which continues to evaluate the potential of Kisqali treatment in new patient populations."

Results from the Phase III MONALEESA-7 trial in premenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer will be presented for the first time in a late-breaker oral presentation.

First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial [Abstract #S2-05; Wednesday, December 6, 4:15 – 4:30 PM CST]
Additional abstracts from across the breast cancer portfolio include:

Kisqali (ribociclib)*

First-line ribociclib + letrozole in hormone receptor-positive, HER2-negative advanced breast cancer: Efficacy by baseline circulating tumor DNA alterations in MONALEESA-2 [Abstract #PD4-06; Thursday, December 7, 7:00 – 9:00 AM CST]
Subsequent treatment for postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer who received ribociclib + letrozole vs placebo + letrozole in the phase III MONALEESA-2 study [Abstract #P5-21-18; Friday, December 8, 5:00 – 7:00 PM CST]
Efficacy and safety of ribociclib plus letrozole in US patients enrolled in the MONALEESA-2 study [Abstract #P5-21-27; Friday, December 8, 5:00 – 7:00 PM CST]
Quality of life and patient-reported outcomes in US patients enrolled in the MONALEESA-2 study [Abstract #P1-13-12; Wednesday, December 6, 5:00 – 7:00 PM CST]
EarLEE-2: A phase 3 study of ribociclib + endocrine therapy (ET) for adjuvant treatment of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), intermediate-risk, early breast cancer (EBC) [Abstract #OT3-05-06; Friday, December 8, 5:00 – 7:00 PM CST]
Patient-centered initiatives for improving trial participation of diverse patient populations in the open-label phase 3b CompLEEment-1 study of ribociclib plus letrozole in the treatment of HR+/HER2- advanced breast cancer [Abstract #P4-10-07; Friday, December 8, 7:00 – 9:00 AM CST]
Afinitor (everolimus)

Serum activin A and outcomes in HR+/HER2- metastatic breast cancer patients treated with everolimus: Results from BOLERO-2 [Abstract #P1-07-09; Wednesday, December 6, 5:00 – 7:00 PM CST]
Ribociclib in combination with everolimus and exemestane in men and postmenopausal women with HR+/HER2- advanced breast cancer following progression on a CDK4/6 inhibitor: Efficacy and updated safety and pharmacokinetic results from phase 1 of the TRINITI-1 study [Abstract #PD5-11; Thursday, December 7, 5:00 – 7:00 PM CST]
Tykerb (lapatinib)**

Copy number aberration analysis to predict response to neoadjuvant anti-HER2 therapy: results from the NeoALTTO phase III trial [Abstract #S1-04; Wednesday, December 6, 10:15 – 10:30 AM CST]
Circulating tumor DNA in HER2 amplified breast cancer: A translational research substudy of the NeoALTTO phase III trial [Abstract #PD3-03; Thursday, December 7, 7:00 – 9:00 AM CST]
Alpelisib (BYL719)

BYLieve: A phase 2 study of alpelisib with fulvestrant or letrozole for treatment of PIK3CA mutant, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (aBC) progressing on/after cyclin-dependent kinase (CDK)4/6 inhibitor therapy [Abstract #OT3-05-02; Friday, December 8, 5:00 – 7:00 PM CST]
Alpelisib plus letrozole in estrogen receptor-Positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (aBC): Safety and preliminary efficacy analysis from a phase 1b trial [Abstract #P5-21-06; Friday, December 8, 5:00 – 7:00 PM CST]
LSZ102

Phase I/Ib study of the SERD LSZ102 alone or in combination with ribociclib in ER+ breast cancer [Abstract #P5-21-04; Friday, December 8, 5:00 – 7:00 PM CST]
Product Information
Approved indications for products vary by country and not all indications are available in every country. The product safety and efficacy profiles have not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that compounds will become commercially available with additional indications.

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Alpelisib (BYL719), buparlisib (BKM120) and LSZ102 are investigational compounds. Efficacy and safety have not been established. There is no guarantee these compounds will become commercially available.

About Novartis in Advanced Breast Cancer
For more than 25 years, Novartis has been at the forefront of driving scientific advancements for breast cancer patients and improving clinical practice in collaboration with the global community. With one of the most diverse breast cancer pipelines and the largest number of breast cancer compounds in development, Novartis leads the industry in discovery of new therapies and combinations, especially in HR+ advanced breast cancer, the most common form of the disease.

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