On June 4, 2017 F-star, a biopharmaceutical company developing novel bispecific antibodies, reported a new partnership with Merck, a leading science and technology company, for the development and commercialisation of five bispecific immuno-oncology antibodies (mAb2) (Press release, f-star, JUN 4, 2017, View Source [SID1234526902]).

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Under the agreement and upon delivery of pre-defined data packages, Merck has the option to acquire five of F-star’s bispecific programmes. This option includes exclusive development and commercialisation rights to F-star’s preclinical lead asset FS118, which is designed to block LAG-3 (Lymphocyte-Activation Gene 3) and PD-L1 (Programmed Death-Ligand 1), two pathways commonly used by cancer cells to evade the immune system. In a preclinical model, F-star has demonstrated that FS118 could improve efficacy compared to monotherapy combinations, which supports the potential to initiate a clinical development programme (1).

Upon option exercise, in addition to FS118, F-star grants Merck exclusive development and commercial rights to four novel bispecific antibodies targeting specific pathways to augment the anti-tumour immune response. In return, Merck will pay up to €115m in upfront, R&D funding and milestone payments in the first two years, and make further payments upon exercising its option and based on milestones.

John Haurum, CEO of F-star, said: "This immuno-oncology collaboration expands our strong relationship with Merck and is a further validation of the potential of F-star’s bispecific antibody platform. Our vision is to transform the treatment of cancer. This is the objective of partnering our lead asset FS118 and other next-generation immuno-oncology compounds with Merck.
This deal also underscores the attractiveness of our asset-centric business model, which provides a flexible deal-making framework whilst at the same time maximising the value of F-star’s bispecific programmes and technology platform. This approach also provides us with additional non-dilutive cash to support our investment in the development of our own pipeline of bispecific antibodies, with a strong focus on immuno-oncology."

This collaboration with Merck is held within F-star’s fourth asset centric vehicle, F-star Delta. Upon the delivery of a pre-defined data package, Merck has an option to acquire the bispecific programmes through the acquisition of F-star Delta and will make further payments upon option exercise as well as milestones with the potential total deal value reaching over €1 billion.

Luciano Rossetti, Executive Vice President, Global Head of Research & Development at the biopharma business of Merck, commented: "Our collaboration with F-star will help us to rapidly enhance our pipeline and grow our portfolio of bispecific immunotherapies. This deal complements our internal capabilities in immuno-oncology and positions us as a potential leader in this important area of research."

On June 4, 2017 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi reported positive preliminary results with investigational REGN2810, a checkpoint inhibitor targeting PD-1 (programmed death 1), in patients with advanced cutaneous squamous cell carcinoma (CSCC) (Press release, Regeneron, JUN 4, 2017, View Source [SID1234519442]). The data, pooled from two expansion cohorts of the REGN2810 Phase 1 trial, will be presented today at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago during an oral presentation (Abstract #9503). REGN2810 is also being investigated in EMPOWER-CSCC 1, an ongoing Phase 2 potentially pivotal, single-arm, open label clinical trial that is currently enrolling advanced CSCC patients.

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Treatment with REGN2810 led to an investigator-assessed overall response rate (ORR) of 46.2 percent (12 of 26 patients, including 2 complete responses, 9 partial responses and 1 unconfirmed partial response) and a disease control rate (DCR) of 69.2 percent (18 of 26 patients, including 12 ORR and 6 stable disease). The median progression free survival and overall survival were not reached at the data cutoff date with a median follow up of 6.9 months (range: 1.1 to 13.8 months; ongoing). One patient experienced progressive disease during treatment with REGN2810 after the initial response, and two patients were not evaluable due to death, which was considered unrelated to REGN2810. Ten patients remain in response as of the data cutoff date (range: 8 to 40 weeks duration of response).

The most common treatment-related adverse event of any grade was fatigue (23.1 percent). All grade 3 or higher adverse events occurred once and included arthralgia (3.8 percent), maculopapular rash (3.8 percent), asthenia (3.8 percent), aspartate aminotransferase (AST) elevation (3.8 percent) and alanine aminotransferase (ALT) elevation (3.8 percent).

"Cutaneous squamous cell carcinoma or CSCC is the second deadliest skin cancer after melanoma, according to the most recent data available," said Kyriakos P. Papadopoulos, M.D., Senior Clinical Investigator at South Texas Accelerated Research Therapeutics (START) and the study presenter. "There are limited treatments and no established standards of care for advanced stages of this disease. CSCC has one of the highest mutation rates reported for any cancers, likely contributing to the study findings, which represent a high responder rate to a PD-1 antibody in a solid tumor cancer. These results are promising and suggest the PD-1 pathway is an important therapeutic target in these patients."

No apparent association between the objective response and level of PD-L1 (programmed death ligand 1) expression was found. PD-L1 expression by immunohistochemistry (22C3 clone, Dako) was performed in tumor cells for 21 expansion cohort patients, with 81 percent of patients (17 of 21) having greater than or equal to 1 percent positive PD-L1 expression. Additional correlative studies are in process.

This Phase 1 study was designed with an initial dose-escalation portion followed by multiple expansion cohorts that were opened to investigate safety and antitumor activity in specific patient populations. These results are from 10 patients with distantly metastatic CSCC who were enrolled in one expansion cohort (Cohort 7) and 16 patients with inoperable (unresectable) locally or regionally advanced CSCC who were enrolled in a second expansion cohort (Cohort 8). All expansion cohort patients were treated with 3 mg/kg doses of REGN2810 by intravenous infusion over 30 minutes every two weeks for up to 48 weeks.

REGN2810 is a human, monoclonal antibody targeting the checkpoint inhibitor PD-1 and is being jointly developed by Regeneron and Sanofi under a global collaboration agreement. REGN2810 is currently being explored as a monotherapy for multiple cancers – including cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC) and non-small cell lung cancer (NSCLC) – as well as in combination with REGN3767, another investigational immunotherapy targeting the checkpoint inhibitor LAG-3 (lymphocyte-activation gene 3).

REGN2810 and REGN3767 are currently under clinical development, and their safety and efficacy have not been fully evaluated by any regulatory authority.

About CSCC
CSCC is the second most common type of skin cancer in the United States. Although CSCC has a good prognosis when caught early and removed with surgery, it can prove especially aggressive when it progresses to advanced stages. Patients at this stage can be disfigured due to multiple surgeries to remove skin-surface tumors on the head, neck and other parts of the body. CSCC is responsible for the most deaths among non-melanoma skin cancer patients.

On June 4, 2017 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that its BRACAnalysis CDx companion diagnostic test successfully identified BRCA-mutated patients with HER2- metastatic breast cancer in the OlympiAD trial (NCT02000622) who responded better to treatment with olaparib than standard chemotherapy (Press release, Myriad Genetics, JUN 4, 2017, View Source [SID1234519454]).

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OlympiAD compared olaparib (300mg twice daily) to physician’s choice of a standard chemotherapy (capecitabine, vinorelbine or eribulin) in the treatment of 302 patients with HER2-negative metastatic breast cancer harboring germline BRCA1/2 mutations as determined by Myriad’s BRACAnalysis CDx companion diagnostic test. The results showed that BRCA-positive patients treated with olaparib had a statistically-significant and clinically-meaningful PFS benefit of compared to the control group.

"In this study, patients with BRCA mutations experienced significantly prolonged PFS when treated with olaparib versus standard of care chemotherapy," said Johnathan Lancaster, M.D., Ph.D., chief medical officer, Myriad Genetic Laboratories. "Based on these findings, all patients with metastatic breast cancer should know their BRCA status as it will be a critical factor in guiding therapy selection for patients with metastatic breast cancer."

It is estimated there are approximately 60,000 patients per year in the United States who are newly diagnosed with or progress to HER2- metastatic breast cancer. Of these patients, two-thirds are not eligible for BRCA testing based upon current testing criteria. If approved by the FDA as a new indication this would potentially triple the number of patients with metastatic breast cancer who are candidates for BRCA testing.

"We believe the results from the OlympiAD study will expand the population who can benefit from the BRACAnalysis CDx test, and the results will help doctors improve care for their patients with metastatic breast cancer," said Lancaster. "This study further supports the use of advanced biomarkers, like BRACAnalysis CDx, to enable precision medicine, which benefits both patients and the healthcare ecosystem."

The collaboration between Myriad and AstraZeneca to develop a novel companion diagnostic test for olaparib began in 2007. OlympiAD is the first Phase 3 trial to demonstrate the clinical utility of the BRACAnalysis CDx test outside of ovarian cancer for which the test was approved by the U.S. Food and Drug Administration (FDA) in Dec. 2014. Based on the robustness of the OlympiaAD results, Myriad plans to submit a supplementary premarket approval (sPMA) application under its existing PMA for BRACAnalysis CDx to include the HER2- metastatic breast cancer indication.

About BRACAnalysis CDx
BRACAnalysis CDx is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Single nucleotide variants and small insertions and deletions (indels) are identified by polymerase chain reaction (PCR) and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR. Results of the test are used as an aid in identifying ovarian cancer patients with deleterious or suspected deleterious germline BRCA variants, who are or may become eligible for treatment with Lynparza (olaparib). This assay is for professional use only and is to be performed only at 320 Wakara Way, Salt Lake City, UT 84108.

About Lynparza
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells. Lynparza is currently approved by regulatory health authorities in the EU for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. It is also approved in the US as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Lynparza is currently being investigated in another separate non-metastatic breast cancer Phase III study called OLYMPIA. This study is still open and recruiting patients internationally.

On June 4, 2017 Y-mAbs Therapeutics, Inc. (YmAbs), an immunotherapy company discovering and developing innovative treatments for patients with cancer, reported positive top line results from a pivotal study of 131I-burtomab in Refractory Leptomeningeal Metastasis from Neuroblastoma (Press release, Y-mAbs Therapeutics, JUN 4, 2017, View Source;study-of-burtomab-in-refractory-leptomeningeal–metastasis-from-neuroblastoma/ [SID1234519467]). Results showed a 58 months average survival for the patients treated with 131I-burtomab in the study, compared to an average of 4.7 month and no long term survival or cure, for a contemporary cohort in the Central German Childhood Cancer Registry . After more than a decade of follow-up, data shows more than 40% overall long term survival indicating that the treated children have been cured.

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At ASCO (Free ASCO Whitepaper), Dr. Kim Kramer from Memorial Sloan Kettering Cancer Center (MSK) presented the overall survival data from 80 pediatric patients with CNS and leptomeningeal metastasis from neuroblastoma treated at MSK with 131I-burtomab, and Prof. Dr. med. Frank Berthold from the University of Cologne presented comparable historical data from the Central German Childhood Cancer Registry, thereby demonstrating that the use of 131I-burtomab led to a multi-fold increase of the average survival in this patient population, where no other established therapy exists.

YmAbs Founder, President and Head of Business Development and Strategy, Thomas Gad said, "Having witnessed this out-patient treatment first hand as a parent, these data provide a potential curative treatment addressing an unmet medical need for a life-threatening disease to children suffering from Refractory Leptomeningeal Metastasis from Neuroblastoma. YmAbs is now positioned to seek the most efficient route to approval. This could be a potential game changer for pediatric patients and their families."

Dr. Claus Møller, Chief Executive Officer further notes, "In a setting, where no other therapies are approved, this survival data represents a true breakthrough and hope for these children."

On June 3, 2017 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported the presentation of positive results from an ongoing Phase II clinical trial (Translational Breast Cancer Research Consortium TBCRC 022) of Puma’s investigational drug PB272 (neratinib) for the treatment of HER2-positive metastatic breast cancer that has metastasized to the brain (Press release, Puma Biotechnology, JUN 3, 2017, View Source [SID1234519409]). The data were presented today in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2017 Annual Meeting in Chicago, Illinois.

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The multicenter Phase II clinical trial enrolled patients with HER2-positive metastatic breast cancer who have brain metastases. The trial is being performed by the TBCRC and enrolled three cohorts of patients. Patients in the first cohort (n=40) included those with progressive brain metastases who were administered neratinib monotherapy. Data from this cohort were previously reported at the 2014 ASCO (Free ASCO Whitepaper) Annual Meeting and published in the Journal of Clinical Oncology in 2016. Patients in the second cohort (n=5) represent patients who had brain metastases which were amenable to surgery and who were administered neratinib monotherapy prior to and after surgical resection. The third cohort (target enrollment=60) enrolled two sub-groups of patients (prior lapatinib-treated and no prior lapatinib) with progressive brain metastases who were administered neratinib in combination with the chemotherapy drug capecitabine. The oral presentation reflects only the patients in the third cohort of patients without prior lapatinib exposure (cohort 3A, n=37), who all had progressive brain metastases at the time of enrollment and who received the combination of capecitabine plus neratinib. A full copy of the oral presentation that was presented at the ASCO (Free ASCO Whitepaper) Annual Meeting is available on the Puma Biotechnology website. Results from the second cohort and cohort 3B (prior lapatinib-treated) will be presented at a forthcoming medical meeting.

In cohort 3A, 30% of the patients had received prior craniotomy, 65% of the patients had received prior whole brain radiotherapy (WBRT), and 35% had received prior stereotactic radiosurgery (SRS) to the brain. No patients had received prior treatment with lapatinib.

The primary endpoint of the trial was central nervous system (CNS) Objective Response Rate according to a composite criteria that included volumetric brain MRI measurements, steroid use, neurological signs and symptoms, and RECIST evaluation for non-CNS sites. The secondary endpoint of the trial was CNS response by Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) Criteria. The efficacy results from the trial showed that 49% of patients experienced a CNS Objective Response by the composite criteria. The results also showed that the CNS response rate using the RANO-BM criteria was 24%. The median time to CNS progression was 5.5 months and the median overall survival was 13.5 months, though 49% of patients remain alive and survival data are immature.

The results for cohort 3A showed that the most frequently observed severe adverse event for the 37 patients evaluable for safety was diarrhea. Patients received antidiarrheal prophylaxis consisting of high dose loperamide, given together with the combination of capecitabine plus neratinib for the first cycle of treatment in order to try to reduce the neratinib-related diarrhea. Among the 37 patients evaluable for safety, 32% of the patients had grade 3 diarrhea and 41% had grade 2 diarrhea.

"Neratinib given in combination with capecitabine showed promising activity in patients with heavily pre-treated HER2-positive disease metastatic to the CNS," said Rachel A. Freedman, MD, MPH, Breast Oncology Center, Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute. "Despite the introduction of several new treatments for patients with HER2-positive metastatic breast cancer, CNS progression events remain a major source of patient morbidity and mortality. Based on the results from TBCRC-022, we look forward to additional trials with neratinib-based regimens for HER2-positive CNS disease."

"We are very pleased with the activity seen in this trial with the combination of neratinib plus capecitabine," said Alan H. Auerbach, CEO and President of Puma Biotechnology. "As a small molecule that can cross the blood brain barrier, neratinib potentially offers patients with HER2-positive metastatic breast cancer that has metastasized to the CNS a novel HER2 targeted treatment option. We look forward to working with TBCRC on future trials of neratinib in patients with HER2-positive disease metastatic to the CNS."