On May 22, 2017 Nektar Therapeutics (NASDAQ: NKTR) reported that Takeda Pharmaceutical Company Limited (TSE: 4502) and Nektar have entered into a research collaboration to explore the combination of Nektar’s lead immuno-oncology candidate, the CD122-biased agonist NKTR-214, with five oncology compounds from Takeda’s cancer portfolio (Press release, Nektar Therapeutics, MAY 22, 2017, View Source [SID1234519255]). The two companies will explore the anti-cancer activity of NKTR-214 with five different targeted mechanisms in preclinical tumor models of lymphoma, melanoma and colorectal cancer.

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"We look forward to collaborating with Takeda to explore a range of combination therapy approaches in models of both liquid and solid tumors," said Jonathan Zalevsky, PhD, Senior Vice President of Biology and Preclinical Development. "Importantly, this research collaboration will allow us to understand the potential of NKTR-214 with key compounds in the Takeda oncology portfolio, including a SYK-inhibitor and a proteasome inhibitor, and identify which combination treatment regimens show the most promise for possible advancement into the clinic."

"We see significant potential in Nektar’s unique CD122-biased agonist in particular the ability to stimulate tumor-killing T-cells in the tumor micro-environment itself," said Phil Rowlands, PhD, Head, Oncology Therapeutic Area Unit, Takeda. "Research partnerships are an important part of helping us advance our aspiration of curing cancer. Working together with Nektar will enable us to identify combinations with exciting preclinical activity and help us achieve Takeda’s goal of developing innovative, targeted therapies to treat people with cancer."

Under the terms of the collaboration, the companies will share costs related to the preclinical studies and each will contribute their respective compounds to the research collaboration. Nektar and Takeda will each maintain global commercial rights to their respective drugs and/or drug candidates.

NKTR-214 is an investigational immuno-stimulatory therapy designed to expand specific cancer-fighting CD8+ effector T cells and natural killer (NK) cells directly in the tumor micro-environment and increase expression of PD-1 on these immune cells. NKTR-214 targets CD122 specific receptors found on the surface of these cancer-fighting immune cells in order to stimulate their proliferation. In clinical and preclinical studies, treatment with NKTR-214 resulted in expansion of these cells and mobilization into the tumor micro-environment.1,2,3 NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

Takeda signed the research collaboration agreement with Nektar Therapeutics through its wholly-owned subsidiary, Millennium Pharmaceuticals, Inc.

On May 22, 2017 BioLineRx Ltd. (NASDAQ/TASE:BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported the filing of regulatory submissions required to commence a Phase 1b trial for BL-8040 in combination with atezolizumab (Tecentriq), Genentech, a member of the Roche Group’s anti-PDL1 cancer immunotherapy, for the maintenance treatment of patients with acute myeloid leukemia (AML) who have achieved complete response following induction therapy (Press release, BioLineRx, MAY 22, 2017, View Source [SID1234519254]). The trial, named BATTLE, is expected to commence in the second half of 2017, following receipt of regulatory approval.

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This clinical study is part of BioLineRx’s cancer immunotherapy collaboration with Genentech to conduct several Phase 1b studies investigating BL-8040 in combination with atezolizumab in multiple cancer indications, announced in September 2016. The Phase 1b study will evaluate the clinical response, safety and tolerability of the combination of these therapies, as well as multiple pharmacodynamic parameters.

BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown, in a successful Phase 2a study in relapsed and refractory AML patients, to be a robust mobilizer of immune and tumor cells and to be effective in inducing direct tumor cell death. These two effects, when combined with atezolizumab-induced blockade of the interaction between PD-L1 with PD-1 and B7.1, are hypothesized to have a beneficial effect on the minimal residual disease (MRD) status of AML patients. Specifically, this combined approach could potentially reduce an AML patient’s MRD status from positive to negative, and possibly have a favorable effect on disease outcome. This study’s regimen aims at further prolonging the period of remission, exploring a novel maintenance approach to these patients.

Philip Serlin, Chief Executive Officer of BioLineRx, stated, "Our collaboration with Genentech in multiple cancer indications is on target and advancing as planned. Our robust partnership with a world leader in cancer immunotherapy is very exciting, and we are looking forward to initiating this combination study, which will hopefully demonstrate the potential to expand the benefit of immunotherapy to cancer patient populations that currently do not benefit from cancer immunotherapy treatments."

About BL-8040
BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and stem cell mobilization. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing cell death (apoptosis). In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

About Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and is the most common type of acute leukemia in adults. According to the American Cancer Society, approximately 20,000 new cases of AML were diagnosed in the United States in 2016, and the median age of AML patients was 67 years old. The first treatment line for patients with AML includes a combination of chemotherapy drugs and is called induction treatment. The median survival for AML patients receiving induction chemotherapy is less than two years, with shorter survival for patients over the age of 60 or for those with certain gene or chromosome aberrations. Due to relapsed or refractory disease (where the disease is not responsive to standard treatments), the overall five-year survival rate for AML is between 10 and 40 percent.

On May 18, 2017 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported that new clinical data on three of its novel tyrosine kinase inhibitors, fruquintinib, savolitinib and sulfatinib, will be presented at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting, to be held in Chicago, Illinois from June 2 to 6, 2017 (Press release, Hutchison China MediTech, MAY 22, 2017, http://www.chi-med.com/presents-data-at-asco-2017/ [SID1234519249]).

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The five presentations, one oral presentation and four poster presentations, cover the following studies:

Fruquintinib:

The full results of the FRESCO Phase III study in 416 patients with locally advanced or metastatic colorectal cancer ("CRC") will be highlighted in an oral presentation on June 5, 2017. Primary endpoint median overall survival was 9.30 months for fruquintinib versus 6.57 months in the control group, with a hazard ratio of 0.65 and p< 0.001. Fruquintinib was well tolerated, with manageable on-target treatment related adverse events consistent with previous studies.
Savolitinib:

c-MET amplification ("amp") is a major acquired resistance ("AR") pathway to Tagrisso (osimertinib). AstraZeneca PLC ("AstraZeneca") will highlight an analysis of 23 EGFR-mutant non-small-cell lung cancer ("NSCLC") patients with AR to Tagrisso. Analysis shows that about 30% (7/23 patients) of AR is c-MET amp and that among the 7 patients with c-MET amp, 3 patients received combination Tagrisso/savolitinib therapy; all 3 had partial response ("PR") under RECIST (Response Evaluation Criteria in Solid Tumors) guidelines.
Savolitinib included in PAPMET Phase II study (sponsored by NIH/NCI) of multiple c-MET and vascular endothelial growth factor receptor ("VEGFR") tyrosine kinase inhibitors in metastatic papillary renal cell carcinoma patients. PAPMET will evaluate four therapies in a 1:1:1:1 randomization, sunitinib, cabozantinib, crizotinib and savolitinib in an about 275-patient study which began in 2016 and as at January 30, 2017 had registered 26 patients. PAPMET will study efficacy, safety and correlation of clinical outcome with tumor molecular driver alterations such as c-MET.
Update on the VIKTORY trial, a biomarker-based umbrella trial in gastric cancer. From June 2014 to January 2017, a total of 432 metastatic gastric cancer patients were enrolled in VIKTORY, a total of 23 patients (5.3%) were guided into savolitinib monotherapy treatment (4/23 patients) or savolitinib/docetaxel combination therapy (19/23) based on molecular screening outcomes.
Sulfatinib:

Preliminary results of a Phase II study in advanced medullary thyroid cancer ("MTC") and radioiodine ("RAI")-refractory differentiated thyroid cancer ("DTC"). Sulfatinib is an oral, novel angio-immuno kinase inhibitor that selectively targets VEGFR, fibroblast growth factor receptor-1 ("FGFR") and colony-stimulating factor-1 receptor ("CSF-1R"). As at December 31, 2016 a total of 18 patients had been enrolled with 1/6 MTC patients and 3/12 RAI-DTC patients reporting confirmed PRs, and all other patients stable disease, under RECIST.
Presentation Details
Abstracts for the presentations are available at abstracts.asco.org, as listed below:

Fruquintinib:

Title: A randomized, double-blind, placebo-controlled, multi-centered phase III trial comparing fruquintinib versus placebo plus best supportive care in Chinese patients with metastatic colorectal cancer (FRESCO)

Abstract #: 3508

Presenter: Dr. Jin Li, Oncologist and Director of the Tumor Department, Shanghai East Hospital, Tongji University School of Medicine

Authors: J Li, S Qin, RH Xu, J Xu, L Shen, Y Bai, Y Deng, L Yang, ZD Chen, H Zhong, H Pan, W Guo, Y Shu, Y Yuan, J Zhou

Session: Gastrointestinal (Colorectal) Cancer – Oral Abstract Session

Date & Time: Monday, June 5, 2017, 5:24 PM CDT

Location: Hall D2



Savolitinib:

Title: MET amplification (amp) as a resistance mechanism to osimertinib

Abstract #: 9020

Authors: Z Piotrowska, K Thress, M Mooradian, RS Heist, CG Azzoli, J Temel, C Rizzo, R Nagy, R Lanman, S Gettinger, T Evans, A Hata, A Shaw, LV Sequist

Session: Lung Cancer—Non-Small Cell Metastatic

Date & Time: Saturday, June 3, 08:00 – 11:30 AM CDT

Location: Hall A

Title: A randomized, phase II efficacy assessment of multiple MET kinase inhibitors in metastatic papillary renal carcinoma (PRCC): SWOG S1500

Abstract #: TPS4599

Authors: SK Pal, C Tangen, IM Thompson, B Shuch, NB Haas, DJ George, M Stein, M Plets, PN Lara

Session: Genitourinary (Nonprostate) Cancer

Date & Time: Sunday, June 4, 08:00 – 11:30 AM CDT

Location: Hall A

Title: VIKTORY trial: Report on AZD1775/paclitaxel in TP53 mutation (+) GC, selumetinib/paclitaxel in ras aberrant GC, AZD5363/paclitaxel in PIK3CA mt and biomarker negative, savolitinib/docetaxel in met (+), and vistusertib/paclitaxel in RICTOR(+) GC

Abstract #: 4024

Authors: J Lee, ST Kim, PG Mortimer, S Hollingsworth, E Harrington, C Shepherd, E Kilgour, SH Park, H Lee, SY Oh, JH Kang, JO Park, YS Park, HY Lim, KM Kim, WK Kang

Session: Gastrointestinal (Noncolorectal) Cancer

Date & Time: Saturday, June 3, 08:00 – 11:30 AM CDT

Location: Hall A



Sulfatinib:

Title: A phase II multicenter trial of the multitargeted kinase inhibitor sulfatinib in advanced medullary thyroid cancer (MTC) and radioiodine (RAI)-refractory differentiated thyroid cancer (DTC)

Abstract #: 6037

Authors: J Chen, Q Ji, J Cao, D Ji, C Bai, Y Lin, B Pan, G Sun, J Li, C Qi, Y Hua

Session: Head and Neck Cancer

Date & Time: Monday, June 5, 1:15 PM CDT

Location: Hall A



Once presented, the presentations will be available at www.chi-med.com/news/. Further information about ASCO (Free ASCO Whitepaper) is available at asco.org.



About Fruquintinib
Fruquintinib is a highly selective small molecule drug candidate that has been shown to inhibit VEGFR 24 hours a day via an oral dose, without known off-target toxicities. Its tolerability, along with its clean drug-drug interaction profile, enables rational combination with other cancer therapies such as in our ongoing clinical trials of fruquintinib in combination with chemotherapy and targeted therapy.

At an advanced stage, tumors secrete large amounts of VEGF, a protein ligand, to stimulate formation of excessive vasculature (angiogenesis) around the tumor to provide greater blood flow, oxygen, and nutrients to the tumor. VEGF and VEGFR play a pivotal role in tumor-related angiogenesis, and the inhibition of the VEGF/VEGFR pathway. This represents an important therapeutic strategy in blocking the development of new blood vessels essential for tumors to grow and invade.

Fruquintinib is currently under joint development in China by Chi-Med and its partner Eli Lilly and Company ("Lilly"). Chi-Med and Lilly jointly announced top-line results from the FRESCO CRC trial on March 3, 2017. In addition, fruquintinib is being studied in China in a Phase III pivotal trial in NSCLC, known as FALUCA; and a Phase II study using fruquintinib combined with Iressa (gefitinib) in the first-line setting for patients with advanced or metastatic NSCLC. Other studies currently being planned, and soon to be initiated, include a Phase III study in gastric cancer in combination with paclitaxel in China, new studies in the United States, and certain exploratory studies in combination with other oncology agents.

About Savolitinib
Savolitinib (AZD6094/HMPL-504) is a potential global first-in-class inhibitor of c-MET (also known as mesenchymal epithelial transition factor) receptor tyrosine kinase, an enzyme which has been shown to function abnormally in many types of solid tumors. It was developed as a potent and highly selective oral inhibitor specifically designed to address issues observed in the clinic with first-generation c-MET inhibitors, including renal toxicity.

Savolitinib was discovered by Chi-Med and is being developed in collaboration with AstraZeneca. AstraZeneca and Chi-Med are currently testing savolitinib in multiple tumor types worldwide including kidney, lung and gastric cancers, both as a monotherapy or in combination with other targeted and immunotherapy agents.

About Sulfatinib
Sulfatinib is an oral, novel angio-immunokinase inhibitor that selectively inhibits the tyrosine kinase activity associated with VEGFR, FGFR and CSF-1R, three key tyrosine kinase receptors involved in tumor angiogenesis and immune evasion. Inhibition of the VEGFR signaling pathway can act to stop angiogenesis, the growth of the vasculature around the tumor, and thereby starve the tumor of the nutrients and oxygen it needs to grow rapidly. Aberrant activation of the FGFR signaling pathway, which can be increased by anti-VEGFR therapy treatment, is shown to be associated with cancer progression by promoting tumor growth, angiogenesis and formation of the myeloid derived suppressor cells. Inhibition of the CSF-1R signaling pathway blocks the activation of tumor-associated macrophages, which are involved in suppressing immune responses against tumors.

Six sulfatinib clinical trials are underway in China and the United States, including two Phase III studies and one Phase II study in neuroendocrine tumors patients (SANET-p, SANET-ep and SANET-1), one Phase II study in thyroid cancer patients and one Phase II study in biliary tract cancer patients.

On May 22, 2017 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that it has completed the dose escalation part of its ongoing Phase I trial evaluating IPH4102 in patients with relapsed/refractory cutaneous T cell lymphomas (Press release, Innate Pharma, MAY 22, 2017, View Source [SID1234519247]). No dose-limiting toxicity was reported and the maximum tolerated dose (MTD) was not reached.

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Full dose-escalation safety results, as well as updated clinical activity data, will be disclosed in an oral presentation at the upcoming International Conference on Malignant Lymphoma (ICML), in Lugano, Switzerland on June 14 at 5:30 pm.

The abstract entitled "Phase I study of IPH4102, anti-KIR3DL2 mab, in relapsed/refractory cutaneous t-cell lymphomas (CTCL): dose-escalation safety, biomarker and clinical activity results" will be available on the ICML online abstract book on June 7.

The cohort expansion part of the trial in patients with transformed mycosis fungoides and Sézary syndrome, with two cohorts of 15 patients, each receiving IPH4102 at the recommended Phase II dose (RP2D) until progression, will start in the upcoming weeks.

Pierre Dodion, Chief Medical Officer of Innate Pharma, commented: "Although CTCL is an orphan disease, the trial has progressed quickly. We are excited by the promising safety profile and efficacy signals of our antibody in this particularly difficult to treat disease. We look forward to the feedback of regulatory authorities on those data and meanwhile are working on the cohort expansion part of the trial which will start shortly."

About IPH4102 Phase I trial:

The Phase I trial (NCT02593045) is an open label, multicenter study of IPH4102 in patients with relapsed/refractory CTCL which is performed in Europe (France, Netherlands and United Kingdom) and in the US. Participating institutions include several hospitals with internationally recognized expertise: the Saint-Louis Hospital (Paris, France), the Stanford University Medical Center (Stanford, CA), the Ohio State University (Columbus, OH), the MD Anderson Cancer Center (Houston, Texas), the Leiden University Medical Center (Leiden, Netherlands), and the Guy’s and St Thomas’ Hospital (London, United Kingdom). 55 patients with advanced CTCL having received at least two prior lines of systemic therapy have been and will be enrolled in two sequential study parts:

The dose-escalation part has accrued 25 KIR3DL2-positive CTCL patients in 10 dose levels. The objective was to characterize IPH4102 safety profile, identify the MTD and/or the RP2D; the dose-escalation followed an accelerated 3+3 design. Preliminary safety and clinical activity results for the first seven dose levels from the dose-escalation part were presented at the 3WCCL and ASH (Free ASH Whitepaper) in 2016;
The cohort expansion part will have 2 cohorts of 15 patients each in 2 CTCL subtypes (transformed mycosis fungoides and Sézary syndrome) receiving IPH4102 at the RP2D until progression.