On June 3, 2019 BioInvent International AB (OMXS: BINV) reported the submission to the U.S. Food and Drug Administration (FDA) of an Investigational New Drug (IND) application for a Phase I/IIa clinical trial of an immune-modulatory anti-FcγRllB antibody in combination with an anti-PD1 antibody in solid tumors (Press release, BioInvent, JUN 3, 2019, View Source [SID1234536820]).

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The anti-FcγRllB antibody is part of BioInvent’s FcγRIIB-targeting program, which has emerged from its F.I.R.S.T platform technology. It simultaneously identifies both targets and high-quality antibodies that bind to them, generating potentially promising new drug candidates.

"There is a strong rationale to improve the therapeutic efficacy of anti-PD1 antibodies, and this study with our first-in-class monoclonal antibody offers the opportunity to improve treatment of solid cancers. It is a further example of how BioInvent’s platform is producing novel immunoregulatory antibody-based cancer therapies which broaden our own pipeline and offer additional licensing and partnering opportunities" says BioInvent’s CEO Martin Welschof.

The Phase I/IIa study is one of four new clinical programs in solid cancers that the Company intends to initiate. These also include BI-1607 (an anti-FcγRllB antibody) in combination with a checkpoint inhibitor; BI-1808 (an anti-TNFR2 antibody); and the collaboration with Transgene to develop oncolytic viruses encoding a validated anti-CTLA-4 antibody.

About BioInvent

On June 3, 2019 Immunocore reported Monotherapy treatment with the first-in-class ImmTAC molecule tebentafusp (IMCgp100) induced an immunologically potent response in patients with advanced uveal and cutaneous melanoma, according to new data presented by Immunocore Limited at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Immunocore, JUN 3, 2019, View Source [SID1234536819]). The biomarker research provides additional insight into the mechanism of action of tebentafusp in patients with advanced melanoma and demonstrates the potential association with clinical outcomes.

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"We are pleased to share new biomarker data from our tebentafusp clinical trial programme, which add to the growing body of evidence supporting the investigational agent’s clinical activity and reinforce the potential applicability of our ImmTAC technology," said Bahija Jallal, Chief Executive Officer of Immunocore. "We recognise the immediate need for new treatment options for people living with metastatic uveal melanoma and are working to advance tebentafusp as quickly and safely as possible."

Tebentafusp is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. Tebentafusp specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma, and is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect T cells to recognise and kill tumour cells. Pivotal tebentafusp clinical trials are currently underway in metastatic uveal melanoma, a rare form of eye cancer.

"Biomarker research is critical to informing the development of new immunotherapy agents, particularly in difficult-to-treat cancers like uveal melanoma," said Mark R Middleton, MD, lead study investigator and Head of the Department of Oncology at the University of Oxford. "These data build a deeper understanding of how the immune system responds to tebentafusp and provide insights needed to inform future enhancements."

ASCO Presentations

Researchers analysed data from the Phase 1 first-in-human clinical trial assessing the safety and tolerability of tebentafusp in 84 HLA-A2+ patients with metastatic melanoma (n=61 cutaneous, n=19 uveal, n=4 other) resistant to standard treatment regimens or for which no standard treatments exist.

Pharmacodynamic Effect of IMCgp100 (TCR–CD3 bispecific) on Peripheral Cytokines and Association with Overall Survival in Patients with Advanced Melanoma

The goal of this analysis was to understand the biological effects of tebentafusp and an association with anti-tumour activity. The findings showed an association between a greater increase in serum CXCL10, a chemokine for T cells expressing CXCR3 receptor, and a greater transient reduction in peripheral CXCR3+CD8+ T cells, tumour shrinkage and longer overall survival (OS). A greater reduction in peripheral CXCR3+ CD8+ T cells also appeared to be associated with tumour shrinkage and longer OS, and changes in tumour biopsies were consistent with T cell infiltration and immune activation.

Relationship Between Clinical Efficacy and AEs of IMCgp100, a Novel Bispecific TCR–anti-CD3, in Patients with Advanced Melanoma

In this analysis, adverse events (AEs) were consistent with tebentafusp’s proposed mechanism of action with most AEs relating to on-target (gp100) off-tumour activity (e.g., rash, pruritus), or were cytokine mediated (e.g., pyrexia, hypotension). There appears to be an association between the timing of onset and resolution of these AEs and certain cytokines in the blood. AEs were generally manageable with standard clinical interventions. An association was also observed between OS and LDH ≤ULN and any-grade rash occurring within 21 days.

"Further understanding of the potential association of mechanism of action with safety and activity is important in the success of novel immune therapies," said Omid Hamid, MD, study investigator and Chief of Translational Research and Immunotherapy at The Angeles Clinic. "These data support the continued investigation of tebentafusp in cutaneous melanoma in addition to the pivotal trials in metastatic uveal melanoma already underway."

More information about the tebentafusp clinical trials can be found at View Source

– Ends –

About Tebentafusp

Tebentafusp is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. Tebentafusp specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma, and is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect T cells to recognise and kill tumour cells. 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 June 3, 2019 VBL Therapeutics (Nasdaq: VBLT), reported that MRI data from VB-111 Phase 2 and Phase 3 studies in recurrent GBM (rGBM), presented yesterday at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, showed a survival benefit associated with objective responses to the compound and a distinct signature of VB-111 activity (Press release, VBL Therapeutics, JUN 3, 2019, View Source [SID1234536818]). The data were presented by Dr. Benjamin M. Ellingson, Ph.D., from the UCLA Brain Tumor Imaging Laboratory (BTIL), Department of Radiological Science.

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The UCLA analysis compared data from VBL’s Phase 2 study of VB-111, which met the primary endpoint of OS benefit with a median OS (mOS) of 414 days, to MRI data from the treatment arm in the GLOBE Phase 3 study, which had a mOS of 6.8 months, despite similar baseline tumor volume between patient cohorts. The goal of the analysis was to investigate the difference between the trial outcomes, using quantitative radiographic tools.

There was a notable difference in the regimens between the studies: in the Phase 2 study, VB-111 was administered first as a single agent therapy (`priming`), with bevacizumab added to VB-111 upon further progression; in contrast, the GLOBE Phase 3 study regimen included co-administration of VB-111 and bevacizumab (Avastin) from the start of study therapy without any VB-111 monotherapy `priming` period.

"Our analyses revealed that responders to VB-111 monotherapy or combination therapy after priming with VB-111 exhibited characteristic, expansive areas of necrosis in areas of initial disease, which are related to the VB-111 mechanism of action," said Dr. Ellingson. "Some patients had clear evidence of response to VB-111 while others showed pseudo-progression, potentially linked to edema and local immune response induced by VB-111, which may have been misinterpreted as disease progression. The data show that responders to VB-111 treatment had a statistically significant survival advantage compared to non-responders."

"This analysis provides independent, quantitative evidence that priming with VB-111 has clinically-meaningful activity in rGBM, which can be seen by MRI signature, and is correlated with a statistically significant survival advantage," said Dror Harats, M.D., Chief Executive Officer of VBL Therapeutics. "We believe this work supports our view that VB-111 has therapeutic potential in rGBM and other difficult to treat and aggressive cancers. The VB-111 program in rGBM is now being advanced in an investigator-sponsored study at leading neuro-oncology centers in the U.S. VBL is also conducting a potential registration study of VB-111 in ovarian cancer, OVAL."

For additional information see: ASCO (Free ASCO Whitepaper) poster

About VB-111 (ofranergene obadenovec)
VB-111, a potential first-in-class anticancer therapeutic candidate, is the Company’s lead oncology product currently being studied in the OVAL potential-registration Phase 3 pivotal trial for ovarian cancer (ClinicalTrials.gov Identifier: NCT03398655). VB-111 has received orphan drug designation in both the US and Europe, and fast track designation in the US for prolongation of survival in patients with rGBM. In addition, VB-111 successfully demonstrated proof-of-concept and survival benefit in Phase 2 clinical trials in radioiodine-refractory thyroid cancer and recurrent platinum-resistant ovarian cancer (NCT01711970). VB-111 has received an Orphan Designation for the treatment of ovarian cancer from the European Commission.

On June 3, 2019 VBL Therapeutics (Nasdaq: VBLT) reported the presentation of the final results from a Phase 1/2 clinical trial of VB-111 in the treatment of patients with recurrent platinum resistant ovarian cancer on Saturday, June 1st at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, in Chicago (Press release, VBL Therapeutics, JUN 3, 2019, View Source [SID1234536817]).

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Data demonstrated a median overall survival (OS) of 498 days in the VB-111 therapeutic-dose arm, versus 172.5 days in the low-dose arm (p=0.03). 58% of evaluable patients treated with the therapeutic dose of VB-111 had a GCIG CA-125 response. In comparison, in the AURELIA trial, the GCIG CA-125 response rate was 31.8% with bevacizumab and chemotherapy, and only 11.6% with chemotherapy alone.

VB-111 activity signals were seen despite unfavorable prognostic characteristics (50% platinum refractory disease and 50% previous treatment with anti-angiogenics). There was a trend for favorable survival in patients who had CA-125 decrease >50% in the VB-111 therapeutic-dose arm (808 vs. 351 days; p=0.067) implicating CA-125 as a valuable biomarker for response to VB-111. Post treatment fever was also associated with a signal for improved survival (808 vs. 479 days; p=0.27).

"The improved overall survival seen with the therapeutic dose of VB-111 is compelling, given that this trial focused on women with poor prognosis whose disease had progressed following several lines of prior therapies," said Tami Rachmilewitz, M.D., Vice President Clinical Development of VBL Therapeutics. "The high CA-125 response rate, the long duration of responses and the recruitment of immune cells into the tumor provide additional evidence for activity of VB-111, and support its continued development in ovarian cancer."

"These data reinforce our confidence in VB-111 as we continue to advance OVAL, our potential registration trial in platinum resistant ovarian cancer," said Dror Harats, M.D., Chief Executive Officer of VBL Therapeutics. "Importantly, the data implicating CA-125 decrease as a biomarker for VB-111 activity can be valuable for our Phase 3 OVAL trial, for which an interim analysis is expected around year-end 2019. In addition, the ability of VB-111 to turn a notoriously `cold` tumor like ovarian cancer `hot` is suggestive that VB-111 may have broader applicability across additional cold tumors. We look forward to the launch of investigator-sponsored trials in rGBM and colon cancer to provide more data on the potential of VB-111."

For additional information see: ASCO (Free ASCO Whitepaper) poster

About VB-111 (ofranergene obadenovec)
VB-111, a potential first-in-class anticancer therapeutic candidate, is the Company’s lead oncology product currently being studied in the OVAL potential-registration Phase 3 pivotal trial for ovarian cancer (ClinicalTrials.gov Identifier: NCT03398655). VB-111 has received orphan drug designation in both the US and Europe, and fast track designation in the US for prolongation of survival in patients with rGBM. In addition, VB-111 successfully demonstrated proof-of-concept and survival benefit in Phase 2 clinical trials in radioiodine-refractory thyroid cancer and recurrent platinum-resistant ovarian cancer (NCT01711970). VB-111 has received an Orphan Designation for the treatment of ovarian cancer from the European Commission.

On June 3, 2019 Stemline Therapeutics, Inc. (Nasdaq: STML), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics, reported that ELZONRIS (tagraxofusp) Phase 2 clinical data in chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF) data are being presented today at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, being held from May 31-June 4, 2019, at McCormick Place in Chicago, Illinois (Press release, Stemline Therapeutics, JUN 3, 2019, View Source [SID1234536814]).

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ELZONRIS (tagraxofusp) is FDA-approved for the treatment of patients, adults and pediatric 2 years and older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN), and is commercially available in the U.S.

Details on the presentations are as follows:

Results from Ongoing Phase 1/2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Relapsed/Refractory Chronic Myelomonocytic Leukemia (CMML)

Abstract: 7059
Session: Hematologic Malignancies – Leukemia, Myelodysplastic Syndromes, and Allotransplant
Presenter: Mrinal M. Patnaik, MBBS; Mayo Clinic
Date: Monday, June 3
Time: 8:00 to 11:00 AM CT
Results from Ongoing Phase 1/2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Intermediate or High Risk Relapsed/Refractory Myelofibrosis (MF)

Abstract: 7058
Session: Hematologic Malignancies – Leukemia, Myelodysplastic Syndromes, and Allotransplant
Presenter: Naveen Pemmaraju, MD; The University of Texas MD Anderson Cancer Center
Date: Monday, June 3
Time: 8:00 to 11:00 AM CT
Please visit our Stemline corporate booth (#19156) during the 2019 ASCO (Free ASCO Whitepaper) annual meeting.

Stemline Provides Further Details on Next Steps for the ELZONRIS CMML Program
Given the encouraging clinical data generated from the ELZONRIS Phase 2 trial in patients with CMML, combined with feedback and guidance from the Food and Drug Administration (FDA), Stemline intends to open a Stage 3 cohort of the currently enrolling 0314 trial to serve as the pivotal program for ELZONRIS in patients with CMML. The planned primary endpoint is overall response rate (ORR); in addition, if certain other endpoints, including spleen size, are shown to have clinical benefit in the initial, Stage 3a, portion of the new cohort, then these endpoints could contribute to the primary evidence of efficacy in the final, Stage 3b, portion of the pivotal program. CD123 levels will also be evaluated in Stage 3a for potential enrichment in 3b.

Stage 3 will enroll patients with previously-treated CMML, and will be a single-arm, non-randomized trial designed to support potential registration. The protocol is currently being designed, and we expect to provide further details, including sample size, during 3Q19, with an expectation of opening the new cohort to enrollment later this year.

Ivan Bergstein, M.D., CEO of Stemline Therapeutics, commented "With ELZONRIS now FDA-approved and commercially available for patients with BPDCN, our focus is on both ensuring patient access to ELZONRIS in the commercial setting as well as broadening the potential for ELZONRIS in additional indications. With this in mind, we are very excited to advance another ELZONRIS clinical program toward a potential second approval, this time in CMML, an aggressive and underserved malignancy."

About ELZONRIS
ELZONRIS (tagraxofusp-erzs), a CD123-directed cytotoxin, is approved by the U.S. Food and Drug Administration (FDA) and commercially available in the U.S. for the treatment of adult and pediatric patients, two years or older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN). For full prescribing information in the U.S., visit www.ELZONRIS.com. In Europe, a marketing authorization application (MAA) is under review by the European Medicines Agency (EMA). ELZONRIS is also being evaluated in additional clinical trials in other indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and acute myeloid leukemia (AML).

About BPDCN
BPDCN is an aggressive hematologic malignancy with historically poor outcomes and an area of unmet medical need. BPDCN typically presents in the bone marrow and/or skin and may also involve lymph nodes and viscera. The BPDCN cell of origin is the plasmacytoid dendritic cell (pDC) precursor. The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, as well as other markers. For more information, please visit the BPDCN disease awareness website at www.bpdcninfo.com.

About CD123
CD123 is a cell surface target expressed on a wide range of myeloid tumors including blastic plasmacytoid dendritic cell neoplasm (BPDCN), certain myeloproliferative neoplasms (MPNs) including chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF), acute myeloid leukemia (AML) (and potentially enriched in certain AML subsets), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). CD123 has also been reported on certain lymphoid malignancies including multiple myeloma (MM), acute lymphoid leukemia (ALL), hairy cell leukemia (HCL), Hodgkin’s lymphoma (HL), and certain Non-Hodgkin’s lymphomas (NHL). In addition, CD123 has been detected on some solid tumors as well as autoimmune disorders including cutaneous lupus and scleroderma.