On December 13, 2019 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology, reported updated data from the triple combination arm of the ongoing Phase 2a COMBAT/KEYNOTE-202 study (Press release, BioLineRx, DEC 13, 2019, View Source [SID1234552344]). The data was delivered today in an oral presentation entitled, "A Multi-Center Phase 2a Trial to Assess the Safety and Efficacy of BL-8040 (a CXCR4 inhibitor) in Combination with Pembrolizumab and Chemotherapy in Patients with Metastatic Pancreatic Adenocarcinoma (PDAC)", at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress (ESMO IO) 2019, which is being held December 11-14 in Geneva, Switzerland. The full presentation is available on the Company’s website.

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Updated Data from the Triple Combo Arm of the COMBAT/KEYNOTE-202 Study
As of today’s date, 36 out of 40 patients have been enrolled in the study. As of December 5, 2019 (the cutoff date for the presentation data), 30 patients were evaluable for safety and 22 were evaluable for efficacy. All patients enrolled were originally diagnosed with stage IV metastatic pancreatic adenocarcinoma (PDAC) and had progressed following first-line treatment with gemcitabine-based chemotherapy.

Best response for the evaluable population of 22 patients showed 7 partial response (PR) and 10 stable disease (SD) patients – resulting in an overall response rate (ORR) of 32% and a disease control rate (DCR) of 77%; this compares favorably to the current chemotherapy standard-of-care treatment (Onivyde/5-fluorouracil/leucovorin) in second-line patients with ORR of 17% and DCR of 52%;

The combination showed continuity of effect – 5 patients with stable disease became partial responders as treatment continued;

Out of the 7 partial responders, 5 are still on treatment, with a current maximum treatment time of 330+ days; and 4 responders showed a reduction in tumor burden of >50%;

Median duration of clinical benefit until progression for the 17 patients with disease control (7 PR and 10 SD patients) is 7.8 months;

The study is ongoing; progression-free and overall survival data remain on track for mid-2020;

The combination was generally well tolerated, with a safety profile consistent with the individual safety profile of each component alone; adverse event (AE) and severe adverse event (SAE) profiles are as expected with chemotherapy-based treatment regimens.

"Metastatic pancreatic cancer has a very poor response to chemotherapy, and immunotherapy treatments have failed to show any effect as single agents," said Manuel Hidalgo, MD, PhD, Chief of the Division of Hematology and Medical Oncology and a Senior Member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and New York-Presbyterian/Weill Cornell Medical Center, and principal investigator of this study. "These promising initial results presented today show an overall response rate double the current chemotherapy standard-of-care treatment in second-line patients. The results are even stronger when taking into account the extended durability of clinical benefit seen to date in this study (median of 7.8 months), compared to approximately three months of response duration with other treatments for second-line pancreatic cancer. I look forward to the survival data expected in mid-2020."

"We are very excited by the positive data accumulating from this triple combination arm of our Phase 2a pancreatic study under our collaboration with Merck," stated Philip Serlin, Chief Executive Officer of BioLineRx. "These data continue to confirm our hypothesis relating to the synergistic effect of cytotoxic chemotherapy, along with the trafficking, tumor microenvironment modulation and T-cell infiltration effects seen in PDAC patients from previous dual combination trials of BL-8040 with checkpoint inhibitors. It is therefore very encouraging to see robust and durable responses to the triple combination treatment, especially as we continue to see a trend of patients receiving treatment for an extended period that move from stable disease to partial response. We hope to see these results translate into an extended survival benefit for these patients, which we expect to announce in mid-2020, and we hope will pave the way for use of immunotherapy in pancreatic cancer and in other cold tumors."

Design of Triple Combination Arm of COMBAT/KEYNOTE-202 Study
The triple combination arm focuses on second-line pancreatic cancer patients and is expected to include approximately 40 patients originally diagnosed with unresectable metastatic pancreatic adenocarcinoma who have progressed following first-line gemcitabine-based therapy. Patients receive BL-8040 monotherapy priming treatment for five days, followed by combination cycles of chemotherapy (Onivyde/5-fluorouracil/leucovorin), KEYTRUDA and BL-8040 until progression. The primary endpoint of the study is the objective response rate (ORR). Secondary endpoints include overall survival, progression free survival, and disease control rate.

The COMBAT/KEYNOTE-202 Study
The Phase 2a COMBAT/KEYNOTE-202 study was originally designed as an open-label, multicenter, single-arm trial to evaluate the safety and efficacy of the combination of BL-8040 and KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada), in over 30 subjects with metastatic pancreatic adenocarcinoma. The study was primarily designed to evaluate the clinical response, safety and tolerability of the combination of these therapies, and was carried out in the US, Israel and additional territories. The study is being conducted by BioLineRx under a collaboration agreement signed in 2016 between BioLineRx and MSD, through a subsidiary.

In July 2018, the Company announced the expansion of its immuno-oncology collaboration with MSD to include the triple combination arm investigating the safety, tolerability and efficacy of BL-8040, KEYTRUDA and chemotherapy as part of the Phase 2a COMBAT/KEYNOTE-202 study.

About BL-8040 in Cancer Immunotherapy
BL-8040 is targeting CXCR4, a chemokine receptor and a well validated therapeutic target that is over-expressed in many human cancers including PDAC. CXCR4 plays a key role in tumor growth, invasion, angiogenesis, metastasis and therapeutic resistance, and CXCR4 overexpression has been shown to be correlated with poor prognosis.

BL-8040 is a short synthetic peptide used as a platform for cancer immunotherapy with unique features allowing it to function as a best-in-class antagonist of CXCR4. It shows high-affinity, long receptor occupancy and acts as an inverse agonist.

In a number of clinical and preclinical studies, BL-8040 has been shown to affect multiple modes of action in "cold" tumors, including immune cell trafficking, tumor infiltration by immune effector T cells, and reduction in immunosuppressive cells (such as MDSCs) within the tumor niche, turning "cold" tumors, such as pancreatic cancer, into "hot" (i.e., sensitizing them to immune checkpoint inhibitors and chemotherapy).

Conference Call and Webcast Information
BioLineRx will hold a conference call today, December 13, 2019 at 8:30 a.m. EST. To access the conference call, please dial +1-888-668-9141 from the U.S. or +972-3-918-0609 internationally. The call will also be available via webcast and can be accessed through the Investor Relations page of BioLineRx’s website. Please allow extra time prior to the call to visit the site and download any necessary software to listen to the live broadcast.

A replay of the conference call will be available approximately two hours after completion of the live conference call on the Investor Relations page of BioLineRx’s website. A dial-in replay of the call will be available until December 15, 2019; please dial +1-888-782-4291 from the U.S. or +972-3-925-5927 internationally.

On December 13, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported the Phase III IMspire150 study, in people with previously untreated BRAF V600 mutation-positive advanced melanoma, met its primary endpoint of progression-free survival (PFS) (Press release, Hoffmann-La Roche, DEC 13, 2019, View Source [SID1234552341]). The study showed adding Tecentriq (atezolizumab) to Cotellic (cobimetinib) and Zelboraf (vemurafenib) helped to reduce the risk of disease worsening or death, compared to placebo plus Cotellic and Zelboraf.

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A significant and clinically meaningful improvement in PFS was demonstrated in the study. The safety profile observed in IMspire150 was consistent with the known safety profiles of the individual medicines. Results from the study will be presented at an upcoming medical meeting and discussed with health authorities, including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).

"By combining a cancer immunotherapy with targeted therapies, we hope to offer a new approach that improves outcomes for people with advanced, BRAF-mutant melanoma." said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development. "We look forward to discussing the results with health authorities around the world."

Roche has an extensive clinical trial development programme for Tecentriq, with more than 50 ongoing studies, including multiple Phase III studies across lung, kidney, skin, breast, colorectal, prostate, ovarian, bladder, blood, liver and head and neck cancers. Studies are evaluating Tecentriq alone and in combination with other medicines.

About the IMspire150 study
IMspire150 is a Phase III, multi-centre, double-blind, placebo-controlled randomised study in people with previously untreated BRAF V600 mutation-positive metastatic or unresectable locally advanced melanoma. The study compared the efficacy and safety of Tecentriq plus Cotellic and Zelboraf to the combination of placebo plus Cotellic and Zelboraf. The primary endpoint of the study was investigator-assessed PFS. Key secondary endpoints include PFS by an independent review committee, overall survival, objective response rate, duration of response and other safety and pharmacokinetic measures.

About advanced melanoma
Melanoma is a less common, but more aggressive and potentially deadly form of skin cancer.1,2,3 When melanoma is diagnosed early, it is generally a curable disease,4,5 but most people with advanced melanoma have a poor prognosis.2 More than 287,000 people worldwide are currently diagnosed with melanoma each year.6 In recent years, there have been significant advances in treatment for advanced melanoma and people with the disease have more options. However, it continues to be a serious health issue with a high medical need and a steadily increasing incidence over the past 30 years.7

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer, and in PD-L1-positive metastatic triple-negative breast cancer.

About Cotellic (cobimetinib)
Cotellic is designed to inhibit MEK1/2, proteins in a cell signalling pathway that helps control cell growth and survival. Cotellic, when used in combination with Zelboraf, is approved in the United States and Europe, as well as many countries around the world, for the treatment of people with melanoma that has spread to other parts of the body or cannot be removed by surgery and has a BRAF V600 mutation. Cotellic was discovered by Exelixis and is being developed by Genentech, a member of the Roche Group, in collaboration with Exelixis.

About Zelboraf (vemurafenib)
Zelboraf is a prescription medicine for the treatment of people with melanoma that has spread to other parts of the body or cannot be removed by surgery and has BRAF V600 mutation. Zelboraf is designed to inhibit some mutated forms of BRAF, which cause abnormal signalling inside cancer cells leading to tumour growth. BRAF is a protein in a cell signalling pathway that helps control cell growth and survival. Zelboraf was the first approved product in its class. Zelboraf was co-developed under a 2006 license and collaboration agreement between Roche and Plexxikon Inc., the small molecule structure-guided R&D centre of the Daiichi Sankyo Group.

On December 13, 2019 Innate Pharma SA (Euronext Paris: IPH – ISIN: FR0010331421; Nasdaq: IPHA) ("Innate" or the "Company") reported an update regarding its TELLOMAK Phase II trial evaluating the efficacy and safety of lacutamab (IPH4102, a potentially first-in-class anti-KIR3DL2 antibody) (Press release, Innate Pharma, DEC 13, 2019, View Source [SID1234552340]). The Company will take the following actions based on ongoing discussions with regulatory authorities regarding a quality issue related to the chemistry, manufacturing and controls (CMC) process:

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Lacutamab will not be administered to new patients in the TELLOMAK trial until additional feedback is received from the respective regulatory agencies overseeing our clinical trial.
Until further notice, the Company will continue to treat patients who are currently enrolled in the multi-center trial, except in Italy where the clinical trial has been suspended due to the feedback from Italian regulatory authorities.
This decision is related to issues with the Company’s manufacturing subcontractor, Rentschler Fill Solutions GmbH or "RFS" (now known as Impletio Wirkstoffabfüllung GmbH). RFS has recently withdrawn the Certificate of Conformity of batches they have produced, including the lacutamab batch currently used in the TELLOMAK trial. RFS was granted a Good Manufacturing Practice (GMP) certificate by the Austrian regulatory agency in August 2018 and further confirmed in October 2019. In parallel, RFS filed for bankruptcy.

The Company’s utmost priority is to ensure patient safety, and no new safety issues have been reported to date in the TELLOMAK trial. An extensive internal and third-party analysis concluded that there was no element that would affect the CMC quality of the product.

Innate will provide an update once it has received additional feedback from the relevant regulatory agencies. In parallel, the Company is working on resolution of the quality issues related to the CMC matter.

On December 23, 2023 3SBio Inc. and Numab Therapeutics ("Numab") reported today on a collaboration agreement, pursuant to which Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd. ("Sunshine Guojian"), a subsidiary of the Company, will develop and commercialize a portfolio of novel multi-specific antibodies for cancer therapy based on Numab’s technology platform (Press release, 3SBio, DEC 12, 2019, View Source [SID1234637791]). Under the agreement, Sunshine Guojian has the right to select up to five antibody molecules emerging from up to three multi-specific antibody programs based on Numab’s R&D platform and has the exclusive licenses to develop and commercialize each of the selected antibody molecules in Greater China territories, including Mainland China, Hong Kong, Macao and Taiwan, while Numab retains exclusive commercial rights in the rest of the world. Concurrently, Sunshine Guojian has invested CHF15M (approximately USD15.2M) in Numab’s series B financing. Dr. Zhenping Zhu, MD, PhD, President of Research and Development, Chief Scientific Officer of 3SBio, has joined the Numab’s board of directors. Further financial terms were not disclosed.

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"Numab’s proprietary MATCH technology has generated a robust pipeline of multi-specific antibody drug candidates with its lead program ND021, an anti-4-1BB x PD-L1 x HSA tri-specific antibody, entering clinical trials in 2020. The alliance with Sunshine Guojian is a continuation of our strategy to work with committed, world-class partners in Asia that are ideally positioned to develop and commercialize our multi-specific antibodies in this important region. Our partnering model has allowed us to establish a growing pipeline of innovative drug candidates and retain key commercial rights in Europe and the US," commented Dr. David Urech, Chief Executive Officer of Numab. "Sunshine Guojian’s investment in our Series B will support Numab in the further expansion and advancement of our portfolio of multi-specific antibodies."

"The investment and collaboration with Numab are consistent with our goal to explore promising therapeutic strategies that address the significant unmet medical needs of cancer patients in China," said Dr. Jing Lou, Chairman and Chief Executive Officer of 3SBio, "Accessing Numab’s cuttingedge multi-specific antibody technology platform and its product portfolio in immune-oncology complements our existing R&D establishment and strategy. 3SBio regards innovation in research and development as a main pillar of the enterprise and we are looking forward to collaborating with the Numab team."

Multi-specific antibodies have the potential to unlock entirely novel modes-of-action aiming at superior benefit-to-risk profiles relative to conventional cancer immune therapies. Numab’s proprietary MATCH technology platform represents one of the most versatile and flexible sources for multi-specific antibodies. MATCH molecules can incorporate up to six binding specificities in true plug-and-play fashion. The individual antibody Fv building blocks are designed for maximum stability and developability.

On December 12, 2019 Genoscience Pharma, a clinical-stage biotechnology company dedicated to discovering and developing anticancer treatment drugs, reported the extension of the Phase 1/2 clinical trial assessing GNS561 to patients with secondary liver cancers (Press release, GenoScience, DEC 12, 2019, View Source [SID1234552424]). Until recently, the current clinical had been enrolling patients with advanced primary liver cancers, i.e. hepatocellular carcinoma and intra-hepatic cholangiocarcinoma. The protocol amendment for extending the clinical study to patients with advanced pancreatic or colorectal cancer with liver metastasis was approved in all countries already participating to the study: USA, Belgium and France. The first patient with metastatic pancreatic cancer has been enrolled since December 10th, 2019 at the Saint-Joseph Hospital.

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"This is a major step for Genoscience Pharma. We were looking forward to extending the indications of our clinical trial to other significant unmet needs in digestive oncology. This approval encourages us to develop our efforts to treat more patients with no satisfactory therapeutic options. It will also improve the inclusion rate, so therapeutic effects are expected to be observed sooner" said Pr Eric Raymond, Chief Medical Officer of Genoscience Pharma.

In addition, the number of patients to be enrolled in Phase 2 was extended to 20 patients per cancer type (hepatocarcinoma, intra-hepatic cholangiocarcinoma, pancreatic cancer with liver metastasis, colorectal cancer with liver metastasis), for a total of 80 patients.

"Such approval to increase in the number of patients to be enrolled is fundamental to enable us achieving our goal to obtain a breakthrough therapy designation for GNS561 from the end of the Phase 2a." said Dr Philippe Halfon, Chief Executive Officer and Founder of Genoscience Pharma.