On May 16, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) has approved Venclexta (venetoclax) in combination with Gazyva (obinutuzumab) for the treatment of people with previously untreated chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) (Press release, Hoffmann-La Roche, MAY 16, 2019, View Source [SID1234536389]).

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"Venclexta plus Gazyva is the only chemotherapy-free option of fixed duration that provides durable responses to help people live longer without progression of their disease, compared to a standard-of-care," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Today’s approval represents our long-standing commitment to helping people with blood cancers throughout the course of their disease, and we are excited to provide this new option for untreated chronic lymphocytic leukaemia."

The approval is based on the results of the randomised phase III CLL14 study, which evaluated 12-month, fixed-duration treatment with Venclexta plus Gazyva compared to Gazyva plus chlorambucil. Results showed the combination of Venclexta plus Gazyva produced a durable and significant reduction in the risk of disease worsening or death (progression-free survival [PFS], as assessed by Independent Review Committee) by 67% compared to Gazyva plus chlorambucil, a current standard-of-care (HR=0.33; 95% CI 0.22-0.51; p<0.0001). Venclexta plus Gazyva showed deep and clinically meaningful responses characterised by a higher rate of minimal residual disease (MRD)-negativity in the bone marrow compared to Gazyva plus chlorambucil (MRD-negativity of 57% vs. 17%) and peripheral blood (MRD-negativity of 76% vs. 35%). MRD-negativity means no cancer can be detected using a specific and highly sensitive test, defined as less than one CLL cell in 10,000 white blood cells.

Results of the study will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2019. The CLL14 study is being conducted in cooperation with the German CLL Study Group (GCLLSG), headed by Michael Hallek, MD, University of Cologne.

The most common adverse reactions with Venclexta plus Gazyva were low white blood cell count, diarrhoea, fatigue, nausea, low red blood cell count, and upper respiratory tract infection.

The FDA rapidly reviewed and approved the supplemental New Drug Application (sNDA) under the FDA’s Real-Time Oncology Review (RTOR) and Assessment Aid pilot programmes. This is the second regimen of Roche medicines approved under the RTOR pilot programme, which is exploring a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. The sNDA was also granted Priority Review, a designation given to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. The FDA previously granted Breakthrough Therapy Designation for Venclexta in combination with Gazyva for the treatment of previously untreated CLL with co-existing medical conditions. Additional submissions of the CLL14 data to health authorities around the world are ongoing.

Venclexta is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche group, in the US and commercialised by AbbVie outside of the US.

About the CLL14 Study
CLL14 (NCT02242942) is a randomised phase III study evaluating the combination of fixed-duration Venclexta plus Gazyva compared to Gazyva plus chlorambucil in patients with previously untreated chronic lymphocytic leukaemia (CLL) and co-existing medical conditions. 432 patients with previously untreated CLL were randomly assigned to receive either a 12-month duration of Venclexta alongside six-month duration of Gazyva (Arm A) or six-month duration of Gazyva plus chlorambucil followed by an additional six-month duration of chlorambucil (Arm B). Arm A started with an initial cycle of Gazyva followed by a five-week Venclexta dose ramp-up to help reduce tumour burden. The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints include PFS assessed by independent review committee (IRC), minimal residual disease (MRD) status, overall response (OR), complete response (with or without complete blood count recovery, CR/CRi), overall survival (OS), duration of response (DOR), event-free survival (EFS), time to next CLL treatment (TTNT) and safety. The CLL14 study is being conducted in cooperation with the German CLL Study Group (GCLLSG), headed by Michael Hallek, MD, University of Cologne.

The most common adverse reactions with Venclexta plus Gazyva were low white blood cell count, diarrhoea, fatigue, nausea, low red blood cell count, and upper respiratory tract infection.

About Venclexta/Venclyxto (venetoclax)
Venclexta/Venclyxto is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumours, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta/Venclyxto blocks the BCL-2 protein and works to restore the process of apoptosis.
Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the US and commercialised by AbbVie, under the brand name Venclyxto, outside of the US. Together, the companies are committed to research with Venclexta/Venclyxto, which is currently being studied in clinical trials across several types of blood and other cancers.

In the US, Venclexta has been granted five Breakthrough Therapy Designations by the US Food and Drug Administration: one for previously untreated CLL, two for relapsed or refractory CLL and two for previously untreated acute myeloid leukaemia.

About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyva/Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system. Gazyva is marketed as Gazyvaro in the EU and Switzerland.

Gazyva/Gazyvaro is currently approved in more than 90 countries in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia, in more than 80 countries in combination with bendamustine for people with certain types of previously treated follicular lymphoma and in more than 70 countries in combination with chemotherapy for previously untreated follicular lymphoma.

Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About the German CLL Study Group (GCLLSG)
Founded in 1996 and headed by Michael Hallek, MD, the GCLLSG has been running various phase III, phase II and phase I trials in chronic lymphocytic leukaemia (CLL) with the goal to provide optimal treatment to patients suffering from this disease. Among those were landmark trials like the CLL8 and the CLL11 trials which led to the current standard of care in CLL. For many years, GCLLSG has been aiming to improve not just the treatment of younger and physically fit patients, but also that of elderly and less fit patients. These patients are generally underrepresented in clinical trials although they constitute the majority of CLL patients treated by doctors in daily practice. The GCLLSG is an independent non-profit research organisation supported by the German Cancer Aid (Deutsche Krebshilfe) www.dcllsg.de.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes polatuzumab vedotin, an anti-CD79b antibody drug conjugate; idasanutlin, a small molecule which inhibits the interaction of MDM2 with p53; T-cell engaging bispecific antibodies targeting both CD20 and CD3, and Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

On May 16, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported positive data from the Phase I/II STARTRK-NG study, evaluating the investigational medicine entrectinib in children and adolescents with recurrent or refractory solid tumours with and without neurotrophic tyrosine receptor kinase (NTRK), ROS1 or anaplastic lymphoma kinase (ALK) gene fusions (Press release, Hoffmann-La Roche, MAY 16, 2019, View Source [SID1234536388]). The study showed entrectinib shrank tumours (objective response rate; ORR) in all children and adolescents who had NTRK, ROS1 or ALK fusion-positive solid tumours (11 of 11 patients), including two patients achieving a complete response.1 Of the 11 patients, five patients with primary high-grade tumours in the central nervous system (CNS) had an objective response, including one patient with a complete response.1 The safety profile of entrectinib was consistent with that seen in previous analyses.1 Data will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on Sunday, 2 June, 2019, from 8:00 – 8:12 am CDT (Abstract 10009), and was part of yesterday’s official ASCO (Free ASCO Whitepaper) presscast.

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"We are encouraged by the results we have seen with entrectinib in children with paediatric and adolescent cancers, including those with tumours in the brain," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "The STARTRK-NG study underscores the importance of combining comprehensive genomic profiling with targeted therapies and supports our approach to providing people with personalised medicines developed specifically for their type of cancer."

Additional data for entrectinib across different tumour types and patient populations will also be presented at ASCO (Free ASCO Whitepaper), highlighting the company’s unique approach to personalised healthcare through advances in targeted therapies, diagnostics and data analytics:

Initial results from an integrated analysis of the Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, evaluating the efficacy of entrectinib in adults with solid tumours and CNS metastases, will be presented on Saturday, 1 June, 2019, in a poster session from 3:00 – 4:30 pm CDT (Abstract 3017).
Results from a Real World Data study, evaluating time-to-treatment discontinuation and progression-free survival as endpoints for comparative efficacy analysis of clinical trials of entrectinib and crizotinib for the treatment of people with ROS1-positive non-small cell lung cancer (NSCLC), will be presented during a poster session on Sunday, 2 June, 2019, from 8:00 – 11:00 am CDT (Abstract 9070).
The FDA recently granted Priority Review for entrectinib for both the treatment of paediatric and adult patients with NTRK fusion-positive, locally advanced or metastatic solid tumours who have either progressed following prior therapies or as an initial therapy when there are no acceptable standard therapies, and for the treatment of people with metastatic ROS1-positive NSCLC.2 These NDAs are based on results from the integrated analysis of the Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials, and data from the STARTRK-NG study. The FDA is expected to make a decision on approval by 18 August, 2019.2

About the STARTRK-NG study
STARTRK-NG is a Phase I/II open-label dose-escalation and expansion study evaluating the safety and efficacy of entrectinib in children and adolescent patients with no curative first-line treatment option, recurrent or refractory extracranial solid tumours or primary CNS tumours, with or without NTRK, ROS1 or ALK fusions.1 Response, assessed by Investigator, was classified as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) using Response Assessment in Neuro-Oncology (RANO) for CNS tumours, Response Evaluation Criteria in Solid Tumors (RECIST), and Curie score (CS) for NBL.1 The study enrolled 29 children and adolescents aged 4.9 months through to 20 years (median age of 7 years) who had recurrent or refractory solid tumours, and 28 were evaluated for response.1 Of the 28 children and adolescents evaluated, 11 children were identified to have tumours with NTRK, ROS1 or ALK fusions and one with ALK F1174L-mutated neuroblastoma (NBL).1 A summary of the results are included below.

Complete responses were observed in 2 patients with tumours harbouring NTRK and ALK fusions: 1 with an NTRK fusion-positive primary CNS tumour and 1 with an ALK fusion-positive inflammatory myofibroblastic tumour. Another complete response was observed in 1 neuroblastoma patient with an ALK F1174L mutation.1
Partial responses were observed in 9 patients, 3 unconfirmed at the time of the clinical cut-off date, across NTRK, ROS1 and ALK fusion-positive primary CNS (n=4) and extracranial (n=5) solid tumours.1
Median duration of therapy for confirmed fusion-positive responders was 10.51 months (3.8 to 17.7 months), and median time to response was 1.89 months (1 to 1.9 months).1
The safety profile of entrectinib was consistent with that seen in previous analyses. Treatment-related adverse events were most frequently National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Grade 1 or 2, leading to discontinuation in 6.9% of patients.1
About NTRK fusion-positive cancer
Neurotrophic tyrosine receptor kinase (NTRK) fusion-positive cancer occurs when the NTRK1/2/3 genes fuse with other genes, resulting in altered TRK proteins (TRKA/TRKB/TRKC) that can activate signaling pathways involved in proliferation of certain types of cancer. NTRK gene fusions are tumour-agnostic, meaning they are present in tumours irrespective of site of origin. These fusions have been identified in a broad range of solid tumour types, including breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.3

About entrectinib
Entrectinib (RXDX-101) is an investigational, oral medicine in development for the treatment of locally advanced or metastatic solid tumours that harbour NTRK1/2/3 or ROS1 gene fusions. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer.4,5 Entrectinib can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions.4,5 Entrectinib is being investigated across a range of solid tumour types, including breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.2,3

Entrectinib has been granted Breakthrough Therapy Designation (BTD) by the FDA; Priority Medicines (PRIME) designation by the European Medicines Agency (EMA); and Sakigake designation by the Japanese health authorities for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or have no acceptable standard therapies.2

On May 16, 2019 Immunocore Limited, a leading T cell receptor (TCR) biotechnology company, reported that it will present new mechanism of action data in advanced uveal and cutaneous melanoma from the tebentafusp clinical research programme at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on 3 June 2019 (Press release, Immunocore, MAY 16, 2019, View Source [SID1234536361]). Tebentafusp (IMCgp100) is a novel bispecific biologic T cell receptor therapy with an anti-CD3 immune-redirecting effector function and specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma.

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"At ASCO (Free ASCO Whitepaper), we will present clinical and biomarker data from our lead bispecific tebentafusp programme that provide insight into its mechanism of action," said David Berman, Head of Research and Development at Immunocore. "We believe these data will translate across our ImmTAC platform and provide another step towards identifying which patient populations benefit."

Poster discussion/poster: Pharmacodynamic effect of IMCgp100 (TCR–CD3 bispecific) on peripheral cytokines and association with overall survival in patients with advanced melanoma (Abstract #9523, Poster #94)

Highlighting new mechanism of action results for tebentafusp (IMCgp100), this poster will be presented by Mark Middleton, MD, Head, Department of Oncology, University of Oxford, on Monday 3 June, 1:15-4:45 p.m. CDT in Hall A.
The poster will also be discussed by Sophie Piperno-Neumann, MD, Department of Medical Oncology, Institut Curie, in the Melanoma/Skin Cancers poster discussion session on Monday 3 June, 4:30-6:00 p.m. CDT in Room E451.
Poster: Relationship between clinical efficacy and AEs of IMCgp100, a novel bispecific TCR–anti-CD3, in patients with advanced melanoma (Abstract #9530, Poster #101)

In a retrospective analysis, reporting the potential association of rash with overall survival and temporal association of key cytokines with cytokine mediated adverse events for tebentafusp (IMCgp100), this poster will be presented by Omid Hamid, MD, Chief of Translational Research and Immunotherapy and Director of Melanoma Therapeutics, Angeles Clinic, in the Melanoma/Skin Cancers poster session on Monday 3 June, 1:15-4:45 p.m. CDT in Hall A.
Analyses presented at the meeting stemmed from a Phase 1 clinical trial assessing the safety and tolerability of tebentafusp (NCT01211262).

About Tebentafusp

Tebentafusp is a novel bispecific biologic T cell redirection therapy with an anti-CD3 immune-redirecting effector function that specifically targets the melanoma associated antigen gp100. It is now in pivotal studies for metastatic uveal melanoma. Tebentafusp has Fast Track Designation and Orphan Drug Designation in the US and Promising Innovative Medicine designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma. For more information about enrolling tebentafusp clinical trials for metastatic uveal melanoma, please visit ClinicalTrials.gov (NCT03070392).

On May 15, 2019 Scintomics GmbH and 1717 Life Science Ventures GmbH reported to have signed an agreement to collaborate in the development of the theranostic pair PentixaFor / PentixaTher (Press release, Scintomics, MAY 15, 2019, View Source [SID1234561514]).

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PentixaPharm GmbH, based in Würzburg, is committed to develop PentixaFor and PentixaTher as a theranostic radiopharmaceutical pair, specifically targeting the CXCR4-receptor expressed in most fast progressing diseases, particularly malignant cancers.

Interviews: "We are delighted that in 1717 LSV we have found a strong partner with an outstanding expertise in the clinical development of precision oncologics. Taking the various recent and successful proof-of-concept studies with PentixaFor and PentixaTher in men into account, this joint venture creates optimal conditions for the effective and swift clinical development of this unrivalled and unique pair of theranostic drugs", said Prof. Hans-Jürgen Wester, PhD, Founder of Scintomics and Chair for Pharmaceutical Radiochemistry at the Technical University of Munich (TUM), Germany.

"The introduction of 68Ga-PentixaFor may be regarded as a milestone for clinical PET imaging of CXCR4 expressing malignancies", added Dr. Hakim Bouterfa Co-founder of 1717 LSV GmbH and CEO of PentixaPharm. "Now we will focus on the next major step to provide CXCR4-directed endoradiotherapy in prospective clinical trials."

About PentixaFor / PentixaTher

This theranostic pair specifically targets the CXCR4-CXCR12 axis, which is significantly involved in the interaction and proliferation of hematologic and solid tumors and their protective environment. The Gallium-68 based PET agent PentixaFor has demonstrated advanced imaging not only for several different hematologic indications – including leukaemia, lymphoma, and multiple myeloma – but also for other solid tumors like adrenocortical carcinoma, and small cell lung cancer. In addition, other disease conditions, such as atherosclerosis, myocardial infarction, splenosis and stroke and can be targeted with this tracer. The therapeutic counterpart PentixaTher, labeled with α- or β-emitters, offers new treatment options for individualised medicine in terms of endoradiotherapy.

On May 15, 2019 The board of directors of LIDDS AB has reported to carry out a directed issue of 641.200 shares at a subscription price of SEK 13.85 per share (Press release, Lidds, MAY 15, 2019, View Source [SID1234555906]). LIDDS will through the directed share issue receive proceeds amounting to SEK 8.9 million, before transaction costs.

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The board of directors of LIDDS has, based on the authorization given by the annual general meeting on May 16, 2018, decided to carry out a directed issue of 641.200 shares to Swedish and international investors.

The subscription price in the Directed Share Issue is set to SEK 13.85 and has been determined by closing market price on May 14, 2019. Through the Directed Share Issue, LIDDS will raise SEK 8.9 million before transaction costs. The subscription price in the Directed Share Issue constitutes no discount compared the closing price on 14 May 2019.

The Directed Share Issue entails a dilution of approximately 2.7 percent of the number of shares and the votes in the Company. Through the Directed Share Issue, the number of outstanding shares and votes will increase by 641,200 shares from 23,051,188 shares to 23,692,388 shares. The share capital will increase by SEK 33,983.60 from SEK 1,221,712.96 to SEK 1,255,696.56.

The reason for the deviation from the shareholders’ preferential rights, is to strengthen the shareholder base and to finance LIDDS’ exciting development projects. The Directed Share Issue will primarily be used to finance the NZ-TLR9 project including the Phase I clinical trial of the same proprietary drug candidate.

Subscribers in the Directed Share Issue are Wikow Invest, BWG Invest together with new and existing large shareholders.

Advisers
Advokatfirman Delphi is legal adviser in connection with the Directed Share Issue.