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 Immunocore Limited, the world’s leading TCR company developing biological drugs to treat cancer and infectious diseases, reported durable tumour responses and strong overall survival data from two Phase I clinical trials of its wholly owned, lead programme, IMCgp100, in metastatic uveal melanoma (Press release, Immunocore, NOV 13, 2017, View Source [SID1234521949]).

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The data, which show a near doubling in the average rate of overall survival compared with studies of other agents, was presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 32nd Annual Meeting on Saturday 11th November 2017, at the Gaylord National Resort & Convention Center in National Harbor, Maryland, USA.

Immunocore’s intra-patient dose escalation Phase I IMCgp100 study in metastatic uveal melanoma patients demonstrates a one-year overall survival (OS) rate of 73% (95% confidence interval [46, 88]) and a one-year progression-free-survival (PFS) rate of 62% based on the irRC criteria as of the data cut-off in October 2017. Median OS has not been reached with median follow-up of 12.8 months in this cohort. The overall survival data from this study compare very favourably to studies with other agents, which show one-year OS rates of approximately 25-45%*.

Pharmacodynamic analysis demonstrated evidence of T cell infiltration and immune activation in tumours after IMCgp100 administration, with persistence of T cell infiltration in the setting of resistance, underpinning confidence in the efficacy observed with the T cell redirection technology of IMCgp100.

Commenting on the results, Dr Richard Carvajal, Head of Experimental Therapeutics at Columbia University, said: "Metastatic uveal melanoma is a condition with exceptionally high unmet medical need with no current standard of care in this setting. No therapies to date have shown survival benefits in trials. The exciting one year overall survival and progression-free survival data we have observed with IMCgp100 have given us confidence to move into pivotal trials measuring survival in this disease setting."

Christina Coughlin, Chief Medical Officer at Immunocore, said: "We believe this therapy has the potential to be a game-changer for medical practice in this devastating condition. At Immunocore, we’re optimistic that the exceptionally strong data we have seen with IMCgp100 in metastatic uveal melanoma have the potential to read across to other ImmTAC programmes, especially when addressing ‘cold’ tumours which are challenging for checkpoint inhibitors and other novel immuno-oncology agents to address. We believe that this underscores the broader applicability of Immunocore’s soluble TCR technology in cancer and beyond."

The details of the clinical trial can be found on clinicaltrials.gov.

Poster Presentation Information

Title: Safety, efficacy and biology of the gp100 TCR-based bispecific T cell redirector, IMCgp100 in advanced uveal melanoma in two Phase 1 trials

Authors: Richard Carvajal, Takami Sato, Alexander N. Shoushtari, Joseph Sacco, Paul Nathan, Marlana Orloff, Pippa Corrie, Neil Steven, Jeff Evans, Jeffrey Infante, Mario Sznol, Clive Mulatero, Omid Hamid, Leonel Hernandez-Aya, Nicola Little, Cheryl McAlpine, David Krige, Namir J. Hassan, Sanjay Patel, Ann-Marie Hulstine, Christina M. Coughlin, Mark R. Middleton

Category: Clinical Trials (Completed)

Date: Saturday 11 November 2017

Time: 12:30 – 14:00 & 18:30 – 20:00

Abstract Number: P208

To view the abstract, please visit the SITC (Free SITC Whitepaper) website at View Source

On November 13, 2017 Curis presented a corporate slide presentation. (Presentation, Curis, NOV 13, 2017, View Source [SID1234521960])

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On November 13, 2017 Syros Pharmaceuticals (NASDAQ: SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of disease-driving genes, reported that the Company will present new preclinical data identifying potential biomarkers predictive of response to SY-1365, its first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor currently in a Phase 1 clinical trial in advanced solid tumors, at the San Antonio Breast Cancer Symposium (SABCS) taking place December 5-9 in San Antonio (Press release, Syros Pharmaceuticals, NOV 13, 2017, View Source [SID1234522012]). The Company will also present on the use of its gene control platform to analyze regulatory regions of the genome in triple negative breast cancer cells and identify potential new drug targets.

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Details on the presentations are as follows:

Date & Time: Wednesday, December 6, from 5-7 p.m. CST
Presentation Title: BCL2L1 (BCL-XL) expression and MYC super-enhancer positivity predict sensitivity to the covalent CDK7 inhibitor SY-1365 in triple negative breast cancer (TNBC) cell lines
Session Title: Treatment: Novel Targets and Targeted agents
Presenter: Nisha Rajagopal, Ph.D., Senior Scientist, Syros
Abstract Number: 1343
Location: Henry B. Gonzalez Convention Center, Hall 1

Date & Time: Thursday, December 7, from 7-9 a.m. CST
Presentation Title: Epigenomic analysis of cancer stem cell (CSC)-enriched triple-negative breast cancer (TNBC) populations reveals gene regulatory circuitry and novel tumor cell vulnerabilities
Session Title: Tumor cell and molecular biology: Epigenetics
Presenter: Matthew Guenther, Ph.D., Principal Scientist, Syros
Abstract Number: 1548
Location: Henry B. Gonzalez Convention Center, Hall 1

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.