On September 20, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that it has entered into a clinical trial collaboration agreement with a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, U.S.A., known as MSD outside the United States and Canada, to evaluate the combination of Daiichi Sankyo’s investigational HER2 targeting antibody drug conjugate DS-8201 and KEYTRUDA (pembrolizumab) in HER2 expressing advanced/metastatic breast and HER2 expressing or HER2 mutant non-small cell lung cancers (NSCLC) (Press release, Daiichi Sankyo, SEP 20, 2018, View Source [SID1234529511]).

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"We are excited to pursue this opportunity to evaluate the safety, tolerability and activity of DS-8201 in combination with KEYTRUDA and whether this combination may provide a potential new treatment approach for patients with HER2 expressing advanced breast and non-small cell lung cancer," said Tom Held, Vice President, Head, Antibody Drug Conjugate Task Force, Oncology Research and Development, Daiichi Sankyo. "Strategic collaborations like this support our goal to pursue, investigate and maximize the application of DS-8201 in combination with other compounds that target different pathways to address unmet needs of patients with cancer."

About the Study

Under the terms of the agreement, Daiichi Sankyo will conduct a two-part phase 1b multicenter, open-label study to:

・ Determine the safety, tolerability and dose of DS-8201 in combination with KEYTRUDA and evaluate efficacy of the combination in patients with HER2 expressing advanced/metastatic breast cancer and patients with HER2 expressing or HER2 mutant advanced/metastatic NSCLC.

・ Enroll patients into one of four cohorts: patients with HER2 positive advanced breast cancer who have been previously treated with ado-trastuzumab emtansine (T-DM1) (cohort 1); patients with HER2 low expressing advanced breast cancer (IHC 1+ or IHC 2+/ISH-) who have received available standard of care (cohort 2); patients with HER2 expressing advanced NSCLC (IHC 1+, 2+, or 3+) who have not received prior treatment with anti-PD-1 or anti-PD-L1 agents (cohort 3); and patients with HER2 mutant advanced NSCLC who have not received prior treatment with anti-PD-1 or anti-PD-L1 agents (cohort 4).

The primary endpoints of the study are maximum tolerated dose/recommended expansion dose and overall response rate. Secondary endpoints include duration of response, disease control rate, progression-free survival, overall survival, time to response and safety. The study is expected to enroll approximately 125 patients in the U.S. and Europe. Additional details of the agreement were not disclosed.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

About DS-8201

DS-8201 is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, DS-8201 is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-8201 is currently in pivotal phase 2 clinical development for HER2 positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01) in North America, Europe and Asia; pivotal phase 2 development for HER2 positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01) in Japan and South Korea; phase 2 development for HER2 expressing advanced colorectal cancer in North America, Europe and Japan; phase 2 development for unresectable and/or metastatic non-squamous HER2 overexpressing or HER2 mutated non-small cell lung cancer (NSCLC) in North America, Europe and Japan; and phase 1 development for other HER2 expressing advanced/unresectable or metastatic solid tumors in the U.S. and Japan.

DS-8201 has been granted Breakthrough Therapy designation for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted therapies including T-DM1 by the U.S. Food and Drug Administration. DS-8201 has also been granted SAKIGAKE Designation by the Japan Ministry of Health, Labour and Welfare for the treatment of HER2 positive advanced gastric or gastroesophageal junction cancer.

DS-8201 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

On September 20, 2018 ERYTECH Pharma (Euronext Paris: ERYP – Nasdaq: ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating drug substances inside red blood cells, reported that the first three patients have been enrolled in its pivotal Phase 3 clinical trial, named ‘TRYbeCA1’, evaluating its lead product candidate eryaspase for the treatment of second line metastatic pancreatic cancer (Press release, ERYtech Pharma, SEP 20, 2018, View Source;p=RssLanding&cat=news&id=2368155 [SID1234529509]).

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The TRYbeCa1 (NCT03665441) trial will enroll approximately 500 patients with second line metastatic pancreatic cancer in 120-130 clinical sites in Europe and the US. Patients who meet the eligibility criteria are randomized 1-to-1 to receive eryaspase in combination with standard chemotherapy (gemcitabine/abraxane or irinotecan -based regimen) or chemotherapy alone until disease progression. The primary endpoint is overall survival. An interim analysis is foreseen when approximately two-thirds of events have occurred.

The launch of the TRYbeCA1 Phase 3 trial follows the positive Phase 2b results in the same patient population, that were reported in September 2017. This open-label, multi-center, 2-to-1 randomized study in 141 patients demonstrated significant improvement in both overall survival and progression-free survival. Overall, eryaspase was well tolerated and showed a safety profile comparable to that of standard chemotherapy.

"The results from our landmark Phase 2b study are highly promising and underscore the importance of targeting tumor metabolism pathways in pancreatic cancer. We are hopeful to provide a novel treatment modality for this highly unmet medical need. We are very pleased that eryaspase has now moved into Phase 3 and patient enrollment has started as planned. Our first three enrolled patients mark the initiation of the trial in Europe. Early next year, we expect sites in the United States will begin enrolling as well," commented Iman El-Hariry, Chief Medical Officer.

About pancreatic cancer

Pancreatic cancer is a disease in which malignant (cancer) cells are found in the tissues of the pancreas. Every year, there are approximately 150,000 new cases of pancreatic cancer diagnosed in Europe and the United States. Advanced pancreatic cancer is a particularly aggressive cancer, with a five-year survival rate of less than 10%. It is currently the fourth leading cause of cancer death in Europe and the United States and is projected to rise to the second leading cause by 2030. Limited therapeutic options are currently available for this indication, thereby reinforcing the need to develop new therapeutic strategies and rational drug combinations with the aim of improving overall patient outcomes and quality of life.

On September 20, 2018 Sesen Bio, Inc. (Nasdaq: SESN), a late-stage clinical company developing fusion protein therapies for the treatment of cancer, reported that the company will present its three-month Phase 3 VISTA Trial data during a poster session at the Global Congress on Bladder Cancer 2018 (Press release, Sesen Bio, SEP 20, 2018, View Source [SID1234529506]). The congress is being held Sept. 20-21, 2018 in Madrid. The ongoing VISTA registration trial is evaluating Vicinium, Sesen Bio’s lead product candidate, for the treatment of people with high-grade non-muscle invasive bladder cancer (NMIBC) who have been previously treated with bacillus Calmette-Guérin (BCG).

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The data, which were presented during a plenary session at the American Urological Association Annual Meeting in May 2018, include a biomarker update showing that nearly all screened patient samples expressed EpCAM, the molecular target of Vicinium.

"We are delighted to present the three-month VISTA Trial data at the Global Congress on Bladder Cancer and further showcase the promise of Vicinium in treating people with NMIBC," said Dr. Thomas Cannell, president and chief executive officer of Sesen Bio. "Today, patients who are unresponsive or become refractory to BCG therapy have virtually one option: complete removal of their bladder. This is a long, challenging and life-altering procedure with a high rate of mortality that nearly half of people who face it choose not to undergo. It is critically important that such people are provided an effective and tolerable option that spares them from having to make such a difficult decision and saves their bladder. We believe that Vicinium holds significant potential as a targeted treatment that could renew the lives of these underserved patients."

As announced in May, the three-month data are from 111 patients in the VISTA Trial with high-grade NMIBC that is either carcinoma in situ (CIS), which is cancer found on the inner lining of the bladder that has not spread into muscle or other tissue, with or without papillary disease, or from patients with papillary disease without CIS, which is cancer that has grown from the bladder lining out into the bladder, but has not spread into muscle or other tissue. In an analysis assessing pooled CIS patients (n=77), based on final U.S. Food and Drug Administration guidance on treatment of BCG-unresponsive CIS NMIBC patients (defined as patients with recurrent CIS within 12 months of adequate BCG therapy)1, Vicinium treatment resulted in a complete response rate of 42 percent at three months. In patients with papillary disease without CIS, treatment with Vicinium demonstrated a 68 percent recurrence-free rate at three months.

In addition, Vicinium has been well-tolerated in the VISTA Trial. Of the treatment-related adverse events in the three-month analysis, four percent were Grade 3 or 4, with no Grade 5 treatment-related adverse events. Four treatment-related serious adverse events were reported, including acute kidney injury or renal failure and cholestatic hepatitis.

About Vicinium
Vicinium (also known as VB4-845), Sesen Bio’s lead product candidate, is a fusion protein being developed for the treatment of high-grade non-muscle invasive bladder cancer (NMIBC). Vicinium is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A (ETA). Vicinium is constructed with a stable, genetically engineered peptide linker to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In clinical trials conducted by Sesen Bio, EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression observed on normal bladder cells. Sesen Bio is currently conducting the Phase 3 VISTA Trial, designed to support the registration of Vicinium for the treatment of high-grade NMIBC in patients who have previously received two courses of bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. Twelve-month data from the trial are anticipated in mid-2019. Additionally, Sesen Bio believes that Vicinium’s cancer cell-killing properties promote an anti-tumor immune response that may potentially combine well with immuno-oncology drugs, such as checkpoint inhibitors. The activity of Vicinium in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.

On September 20, 2018 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that Alan H. Auerbach, Chairman, Chief Executive Officer, President and Founder of Puma, will provide an overview of the Company at 1:10 p.m. EDT on Monday, October 1, at the Cantor Global Healthcare Conference (Press release, Puma Biotechnology, SEP 20, 2018, View Source [SID1234529505]). The conference will be held at the InterContinental New York Barclay Hotel.

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A live webcast of the presentation will be available on the Company’s website at www.pumabiotechnology.com. The presentation will be archived on the website and available for 30 days.

On September 20, 2018 Pierre Fabre reported that the European Commission (EC) has granted marketing authorisation for the combination of BRAFTOVI (encorafenib) and MEKTOVI (binimetinib) for the treatment of adult patients with unresectable or metastatic melanoma with a BRAFV600 mutation, as detected by a validated test (Press release, Pierre Fabre, SEP 20, 2018, View Source [SID1234529504]).1,2 The EC decision is applicable to all 28 European Union (EU) member states plus Liechtenstein, Iceland and Norway.

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"We are extremely pleased that European patients with advanced BRAF-mutant melanoma will now have the combination of BRAFTOVI and MEKTOVI as a new treatment option", said Frédéric Duchesne, President & CEO of the Pierre Fabre Pharmaceuticals Division. "All of us at Pierre Fabre are driven to make a real difference for patients. Bringing more than 30 years of oncology experience and our heritage in dermatology to our partnership with Array BioPharma, we have been able to harness our expertise in order to help men and women living with this devastating disease. Today’s news inspires us to continue pursuing new innovations that will benefit patients".

The EC decision, which follows the positive opinion by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in July, is based on results from the Phase 3 COLUMBUS trial.3 This trial demonstrated that the combination of BRAFTOVI 450 mg once daily and MEKTOVI 45 mg twice daily significantly improved median progression-free survival (PFS), compared with vemurafenib alone 960 mg twice daily (14.9 months versus 7.3 months, respectively: hazard ratio [HR] 0.54, 95% confidence interval [CI], 0.41–0.71; two-sided p<0.0001).3 Data published in The Lancet Oncology4 in September 2018 demonstrated that treatment with BRAFTOVI and MEKTOVI achieved a median overall survival (OS) of 33.6 months, compared with 16.9 months for patients treated with vemurafenib as a monotherapy (HR 0.61, 95% CI, 0.47–0.79; p<0.0001) in the planned analysis of OS in the COLUMBUS trial4. The most common adverse reactions (≥25%) occurring in patients treated with BRAFTOVI administered with MEKTOVI at the recommended dose (n=274 based on two Phase II trials and COLUMBUS) were fatigue, nausea, diarrhoea, vomiting, retinal detachment, abdominal pain, arthralgia, increased blood creatine kinase and myalgia.1,2 In the COLUMBUS trial, adverse events leading to discontinuation that were suspected to be related to the study treatment occurred in 6% of patients.3,4

"The European Commission’s approval is an important advance in improving the prognosis of patients with advanced BRAF-mutant melanoma", said Professor Reinhard Dummer, University of Zürich, Vice-Chairman of the Department of Dermatology in the University Hospital of Zürich, Switzerland, and investigator of the COLUMBUS study. "Physicians and patients will now have BRAFTOVI and MEKTOVI as an effective and well-tolerated treatment combination option, which has been shown to delay disease progression and potentially prolong patients’ lives".

Important safety information and recommendations for the use of BRAFTOVI and MEKTOVI are detailed in the Summary of Product Characteristics (SmPC), published in the European public assessment report (EPAR) and available in all official EU languages.
See full SmPC at: View Source

On 27 June 2018, Pierre Fabre’s partner Array BioPharma, which has exclusive rights for these medicines in the United States (US), announced that the combination of BRAFTOVI and MEKTOVI was approved by the US Food and Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test.5,6 BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma.

About BRAF-mutant Metastatic Melanoma
Melanoma develops when unrepaired DNA damage to skin cells triggers mutations that may lead them to multiply and form malignant tumours. Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates.7,8 There are a variety of gene mutations that can lead to metastatic melanoma. The most common genetic mutation in metastatic melanoma is BRAF. There are more than 100,000 new cases of melanoma diagnosed in Europe each year,9 approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma.10–11

About BRAFTOVI (encorafenib) and MEKTOVI (binimetinib)
BRAFTOVI (encorafenib) is an oral small-molecule BRAF kinase inhibitor and MEKTOVI (binimetinib) is an oral small-molecule MEK inhibitor that targets key enzymes in the MAPK signalling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, including melanoma, colorectal cancer, non-small-cell lung cancer, thyroid and others.

Pierre Fabre has exclusive rights to develop and commercialise BRAFTOVI and MEKTOVI worldwide, except in the US and Canada, where Array BioPharma retains exclusive rights; Israel, where Medison has exclusive rights; and in Japan and South Korea, where Ono Pharmaceutical has exclusive rights to commercialise both products.

BRAFTOVI + MEKTOVI Abbreviated EU Prescribing Information
▼These medicinal products are subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of SmPC for how to report adverse reactions.

Name of the medicinal products: BRAFTOVI (encorafenib) 75 mg hard capsules and 50 mg hard capsules. MEKTOVI (binimetinib) 15 mg film-coated tablets.

Clinical particulars:
Therapeutic indications: Encorafenib in combination with binimetinib is indicated for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

Posology and method of administration: Encorafenib treatment in combination with binimetinib should be initiated and supervised under the responsibility of a physician experienced in the use of anticancer medicinal products. Posology: The recommended dose of encorafenib is 450 mg (six 75 mg capsules) once daily, when used in combination with binimetinib. The recommended dose of binimetinib is 45 mg (three 15 mg tablets) twice daily corresponding to a total daily dose of 90 mg approximately 12 hours apart. Dose modification: The management of adverse reactions may require dose reduction, temporary interruption or treatment discontinuation (for complete information, please refer to SmPC 4.2 section). Method of administration: For oral use. The capsules of encorafenib are to be swallowed whole with water. They may be taken with or without food. The concomitant administration of encorafenib with grapefruit juice should be avoided. The tablets of binimitinib are to be swallowed whole with water. They may be taken with or without food.

Contraindications: Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the BRAFTOVI and MEKTOVI SmPc.

Special warnings and precautions for use: Encorafenib and binimetinib have to be given in combination. Before taking encorafenib in combination with binimetinib, patients must have BRAFV600 mutation confirmed by a validated test. For complete information on the following special warnings and precautions for use: Patients who have progressed on a BRAF inhibitor, patients with brain metastases. Left ventricular dysfunction, Haemorrhage, ocular toxicities. QT Prolongation, New primary malignancies, Cutaneous and non-cutaneous malignancies, Liver laboratory abnormalities, Hepatic impairment, Renal impairment, CK elevation and rhabdomyolysis, Hypertension, Venous thromboembolism (VTE), Pneumonitis/Interstitial lung disease, Lactose intolerance, please refer to BRAFTOVI and MEKTOVI SmPC 4.4 section.

Interaction with other medicinal products and other forms of interaction: Encorafenib is primarily metabolised by CYP3A4. Therefore, concomitant administration of encorafenib with strong CYP3A4 inhibitors should be avoided. Agents that are CYP3A4 substrates (inhibitor and inducer) should be co-administered with caution. Binimetinib is primarily metabolised through UGT1A1 mediated glucuronidation. Therefore, inducers and inhibitors of UGT1A1 should be co-administered with caution. For complete information, please refer to SmPC, 4.5 section.

Undesirable effects: Summary of safety profile: At the recommended dose (n=274) in patients with metastatic melanoma, the most common adverse reactions (≥ 25%) occurring in patients treated with encorafenib administered with binimetinib were fatigue, nausea, diarrhea, vomiting, retinal detachment, abdominal pain, arthralgia, blood CK increased and myalgia. For complete information, please refer to BRAFTOVI and MEKTOVI SmPC 4.8 section.

For complete information please refer to the full SmPC which can be found at: View Source

About COLUMBUS
The COLUMBUS trial (NCT01909453) is a two-part, international, randomised, open-label, Phase 3 trial evaluating the efficacy and safety of BRAFTOVI (encorafenib) in combination with MEKTOVI (binimetinib) compared with vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAFV600 mutation.12 The primary endpoint of the trial was median progression-free survival (PFS); all secondary efficacy analyses, including the prospectively planned analysis overall survival (OS), are descriptive in nature. More than 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the COLUMBUS trial.

The EC decision is based on results from the Phase 3 COLUMBUS trial, which demonstrated that the combination improved median PFS, compared with vemurafenib alone (14.9 months versus 7.3 months, respectively: HR 0.54, 95% CI, 0.41–0.71; p<0.001).1–3 As presented at ASCO (Free ASCO Whitepaper) in June 2018, treatment with BRAFTOVI and MEKTOVI achieved a median OS of 33.6 months, compared with 16.9 months for patients treated with vemurafenib as a monotherapy (HR 0.61, 95% CI, 0.47–0.79; p<0.0001) in the planned analysis of OS in the COLUMBUS trial.1–2,4 Adverse events leading to discontinuation that were suspected to be related to the study treatment occurred in 6% of patients.3,4 The most common Grade 3–4 adverse events, seen in more than 5% of patients, were: increased gamma-glutamyltransferase (9%), increased creatine phosphokinase (7%) and hypertension (6%).3,4