On June 1, 2018 Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported preliminary data from the ongoing metastatic, castration resistant prostate cancer (mCRPC) Phase 1/2 KEYNOTE-046 study, conducted in conjunction with Merck (known as MSD outside the United States and Canada) evaluating ADXS-PSA, Advaxis’s Listeria monocytogenes (Lm)-based immunotherapy, alone and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy (Press release, Advaxis, JUN 1, 2018, View Source [SID1234527023]).

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Findings will be highlighted in a poster discussion at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting underway in Chicago, on Saturday, June 2, from 4:45 pm to 6:00 p.m. CDT (Location: Hall A; Poster #246; Abstract #5019). Principal Investigator and author Naomi Haas, MD, Director of the Prostate and Kidney Cancer Programs and Associate Professor of Medicine at the Hospital of the University of Pennsylvania will be presenting.

ADXS-PSA was tested alone or in combination with KEYTRUDA in an advanced and heavily pretreated patient population who had progressed on androgen deprivation therapy. A total of 13 and 37 patients were evaluated on monotherapy and combination therapy, respectively. Overall, the safety profile was consistent with findings from prior clinical studies using the Lm platform. Treatment-related adverse events (TRAEs) were mostly mild or moderate constitutional symptoms such as fever, chills, rigors, hypotension, nausea and fatigue, consistent with immune activation and manageable with standard care. One patient in the monotherapy arm was discontinued from the study due to a grade 4 TRAE related to cytokine release, which resolved within 24 hours using medical management. There were no new toxicities observed with the combination therapy. In all treated patients, those who received the combination therapy experienced the longest overall survival (OS) at data cut-off, with the median not having been reached at 13 months of follow-up.

"Improvements in the care and treatment of highly refractory prostate cancer, a traditionally difficult type of cancer to treat, are vital. These early results show a safe and tolerable profile for ADXS-PSA alone or in combination with KEYTRUDA," said Dr. Haas. "Albeit the study was not designed to compare monotherapy to combination therapy, the survival rates in the combination therapy arm are encouraging, especially given the reduction in PSA levels observed in this group, and mature data in the following 6 months will help better define the role of ADXS-PSA in combination with KEYTRUDA in mCRPC."

Key Findings from KEYNOTE-046 (as of March 30, 2018):

The advanced patient population in the study had a median Gleason score of 8.3, and was heavily pretreated, with greater than 70% having received three or more prior lines of therapy.
Median overall survival had not been reached in the combination arm after 13 months of follow-up (95%CI 7.16-NR), and was 7.79 months (95%CI 3.52-11.9) in the monotherapy arm.
56.8% of patients on combination therapy and 38.5% of patients on monotherapy did not experience disease progression.
The percentage of patients with PSA declines from baseline in the combination therapy arm was 40.5%, and 15.4% in the monotherapy arm.
In all treated patients, an improvement in survival was observed in patients with PSA declines from baseline of 50% or greater vs. those with PSA declines of less than 50%. There were 7 patients in the combination arm with 50% or greater declines in PSA from baseline, and none in the monotherapy arm.
Previously presented immunologic data from the monotherapy arm of this trial showed that ADXS-PSA induced or enhanced T cell responses not only to PSA, but also to other prostate cancer antigens that were not expressed by the Lm-based vector, which is indicative of antigen cascade or antigen spreading (SITC 2017; Hayes et al. J Immunother Cancer. 2017;5(Suppl 2)86:P2). Correlative immunologic analyses and overall survival for the combination therapy patients are underway.

About KEYNOTE-046

KEYNOTE-046 (NCT02325557) is a Phase 1/2 open-label, multicenter dose determination and expansion trial that evaluates the safety, tolerability and preliminary clinical activity of ADXS-PSA as monotherapy (Part A; n=14 [13 treated]), and in combination with KEYTRUDA (Part B; n= 37) in heavily pretreated patients with progressive and refractory mCRPC. Patient accrual in the study is complete, with 5 patients still receiving treatment, all in Part B, and being followed for survival analysis.

About ADXS-PSA

ADXS-PSA, one of Advaxis’s Listeria monocytogenes (Lm) based immunotherapies, utilizes live, attenuated, bioengineered Lm as a vector to deliver PSA directly to antigen presenting cells. Development is being pursued in a clinical trial collaboration and supply agreement with Merck.

On June 1, 2018 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported that results from a second major clinical validation study of its polygenic riskScore test will be featured in an oral presentation at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago, Ill (Press release, Myriad Genetics, JUN 1, 2018, View Source [SID1234527022]).

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riskScore is an innovative test that combines 86 DNA variants with a person’s family and medical history, to determine a woman’s five-year and lifetime risk of breast cancer. The key finding from this prospective clinical trial is that the riskScore test can accurately predict the five-year and lifetime risk of breast cancer in women who test negative for a hereditary mutation using the myRisk Hereditary Cancer test.

"Women who undergo hereditary cancer testing and test negative for mutations in known breast cancer genes, frequently still have questions about their risk of breast cancer," said Johnathan Lancaster, M.D. Ph.D., gynecologic oncologist and chief medical officer, Myriad Genetics. "riskScore answers many of those questions by providing a definitive risk determination with a test that has been highly validated."

In March, MIT Technology Review magazine named riskScore as one of the top 10 Breakthrough Technologies for 2018. riskScore currently is available for women of European descent and who receive a negative myRisk Hereditary Cancer test result. However, every patient tested with the myRisk Hereditary Cancer test, regardless of ethnicity, will receive their lifetime breast cancer risk estimates according to Tyrer-Cuzick, which is a model that estimates risk based on family history and clinical features. Myriad is working to expand the riskScore test to other ethnicities in the future.

A summary of the oral presentation appears below and more information about the company’s presentation can be found on the ASCO (Free ASCO Whitepaper) website. Follow Myriad on Twitter via @MyriadGenetics and stay informed about symposium news and updates by using the hashtag #ASCO18.

myRisk Hereditary Cancer with riskScore Oral Presentation
Title: Validation of a combined residual risk score for healthy unaffected women presenting to breast cancer screening centers.
Presenter: Kathryn Dalton, DO, Cape Cod Healthcare.
Date: Sunday, June 3, 2018, 8:00—11:00 a.m.
Location: Oral Presentation, 1507

The objective of this study was to independently validate the riskScore test in a prospective, general patient population. riskScore is a novel test that combines data from the Tyrer-Cuzick model with genetic markers, called single nucleotide polymorphisms (SNPs), to comprise a combined risk score that accounts for clinical, familial and genetic variables. The study included 518 women: 256 women recently diagnosed with breast cancer and 262 unaffected women (controls). The results show that riskScore is a highly statistically significant predictor of the 5-year and lifetime risk of breast cancer (p=2.6×10-12 and p=2.5×10-12, respectively). Moreover, riskScore was statistically significantly superior to Tyrer-Cuzick alone for both 5-year and lifetime risk of breast cancer (1.9×10-8 and p=2.4×10-8, respectively), underscoring the independent contribution of the SNPs to the combined test score. Importantly, a separate analysis of the 86 SNPs in the controls showed that about half of those women tested had an increased risk of breast cancer compared to the general population (Graph 1).

Graph 1: Breast Cancer Risk Profile of Unaffected Women

"Individually, the 86 DNA variants may have a small effect on breast cancer risk. However, this study shows that when you combine them, it is possible to more accurately predict a woman’s risk of breast cancer versus relying on family history and clinical features alone," said Kathryn Dalton, DO, lead investigator, and breast surgeon at Cape Cod Healthcare General and Specialty Surgery in Hyannis, MA. "Importantly, this genetic information can be used to identify those women who are at normal risk and can be followed with routine screening and those who are at higher risk and may benefit from additional monitoring."

These results from this new study add to the growing body of evidence in support of riskScore. In December 2017, the first major clinical validation study of the combined clinical risk score (riskScore + Tyrer-Cuzick) was presented at the San Antonio Breast Cancer Symposium. In September 2017, the validation of the SNP genetic markers in more than 17,000 patients was presented at 36th Annual Conference of the National Society of Genetic Counselors.

About riskScore
riskScore is a new clinically validated personalized medicine tool that enhances Myriad’s myRisk Hereditary Cancer test. riskScore helps to further predict a women’s lifetime risk of developing breast cancer using clinical risk factors and genetic-markers throughout the genome. The test incorporates data from more than 80 DNA variants, called single nucleotide polymorphisms, identified through 20 years of genome wide association studies in breast cancer and was validated in Myriad’s laboratory to predict breast cancer risk in women of European descent. This data is then combined with a best-in-class family and personal history algorithm, the Tyrer-Cuzick model, to provide every patient with individualized breast cancer risk.

About Myriad myRisk Hereditary Cancer
The Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 28 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma.

On June 1, 2018 BeiGene, Ltd. (NASDAQ:BGNE), a commercial-stage biopharmaceutical company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that it will present data on its investigational BTK inhibitor zanubrutinib, and host an investor conference call and webcast at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) (Press release, BeiGene, JUN 1, 2018, View Source;p=RssLanding&cat=news&id=2352714 [SID1234527021]). The EHA (Free EHA Whitepaper) meeting will take place June 14-17, 2018 in Stockholm, Sweden.

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Investor Conference Call & Webcast Information:

Date and Time: Friday, June 15, 2018, 8:00 am EDT (Friday, June 15, 2018, 8:00 pm China Standard Time)
Dial-In Numbers: 1-844-461-9930 or 1-478-219-0535 (U.S.), 400-682-8609 or 800-870-0169 (China), 852-30114522 (Hong Kong), 65-66221010 (Singapore), 61-282239773 (Australia), 0856619361 (Stockholm), or 478-219-0535 (International).
Conference ID Number: 7756029
Webcast and Replay: A live webcast and replay of the event will be available on BeiGene’s investor website, View Source The dial-in replay will be available approximately two hours after the conference and will be available for two days following the event. It can be accessed by dialing 1-855-859-2056 (U.S.) or 1-404-537-3406 (International), or 400-683-7185 (China).

Poster Presentations:

Title: Improved Depth of Response with Increased Follow-Up for Patients (PTS) with Waldenström Macroglobulinemia (WM) Treated with Bruton’s Tyrosine Kinase (BTK) Inhibitor Zanubrutinib
Abstract: PS1186
Date: Saturday, June 16, 2018
Time: 17:30 – 19:00 (CEST)
Presenter: Dr. Judith Trotman

Title: Pooled Analysis of Safety Data from Zanubrutinib (BGB-3111) Monotherapy Studies in Hematologic Malignancies
Abstract: PF445
Date: Friday, June 15, 2018
Time: 17:30 – 19:00 (CEST)
Presenter: Dr. Constantine Tam

About Zanubrutinib
Zanubrutinib (BGB-3111) is an investigational small molecule inhibitor of Bruton’s tyrosine kinase (BTK) that is currently being evaluated in a broad pivotal clinical program globally and in China as a monotherapy and in combination with other therapies to treat various lymphomas.

On June 1, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that data from across its genitourinary (GU) and gastrointestinal (GI) cancer immunotherapy development programme will be presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from 1-5 June in Chicago, IL, United States (Press release, Hoffmann-La Roche, JUN 1, 2018, View Source [SID1234527020]). Data to be presented at ASCO (Free ASCO Whitepaper) 2018 demonstrate the potential of the combination of TECENTRIQ (atezolizumab) and Avastin (bevacizumab) in first-line advanced or metastatic renal cell carcinoma (mRCC) and hepatocellular carcinoma (mHCC), as well as show initial data for TECENTRIQ monotherapy as a neoadjuvant treatment in early stage urothelial carcinoma (UC).

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"We are pleased to present positive Patient-Reported Outcomes data from the Phase III IMmotion151 study, which demonstrate the quality of life benefits that TECENTRIQ and Avastin potentially bring to people living with advanced kidney cancer," said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. "We will also present promising early data for TECENTRIQ and Avastin in advanced or metastatic liver cancer, where there is a significant need for new therapies. Data from these two studies provide further evidence to support the potential of this unique combination across multiple settings."

Patient-Reported Outcome (PRO) collected in the Phase III IMmotion151 study investigating the combination of TECENTRIQ and Avastin as a first-line treatment for mRCC, compared with a current standard of care sunitinib, were evaluated in the overall study population and show:

Patients receiving the combination reported a better health-related quality of life (HRQol) overall when compared with sunitinib. HRQol evaluates the overall impact of disease and treatment on patient’s quality of life in terms of disease related symptoms, treatment side effects and function/well-being
Patients receiving the combination reported lower impact of symptoms on day-to-day life, when compared with patients receiving sunitinib
The combination of TECENTRIQ and Avastin markedly increased the time before symptoms meaningfully impacted day-to-day life compared to sunitinib (median time to deterioration: 11.3 vs 4.3 months; HR=0.56; 95% CI: 0.46, 0.68)
Patients receiving the combination had milder and more stable symptom severity overall and a clinically meaningful reduction in the five most severe disease symptoms
Patients completed questionnaires on Days 1 and 22 of each 6-week cycle, at the end of treatment
Earlier this year, Roche announced that IMmotion151 met its co-primary endpoint of investigator-assessed progression-free survival (PFS) when comparing the TECENTRIQ and Avastin combination with sunitinib for people whose disease expressed the PD-L1 (programmed death-ligand 1) protein. The safety profile was consistent with previously reported data, with a discontinuation of the combination regimen only occurring in 5% of the patients and a lower rate of Grade 3-4 treatment-related adverse events with the TECENTRIQ and Avastin combination (40%) than with sunitinib alone (54%). 16% of patients required use of systemic steroids within 30 days of the onset of an immune-related AE.

Further data for TECENTRIQ and Avastin will be presented from an ongoing Phase Ib study evaluating the combination as a first-line treatment in untreated advanced, unresectable or metastatic HCC. In the safety evaluable population (n=43), 28% patients (n=12) experienced Grade 3-4 treatment-related adverse events and no treatment-related Grade 5 adverse events were observed. No new safety signals were identified beyond the established safety profiles for the individual medicines. After a median follow-up of 10.3 months, responses (investigator assessed per RECIST v1.1) were seen in 14 (61%) of 23 efficacy evaluable patients and regardless of disease etiology (cause), region (Asia or US), baseline alpha-fetoprotein levels or spread of tumour beyond the liver. Assessment by independent review facility (IRF) assessed per RECIST v1.1 revealed a response rate of 65% (15 out of 23 patients). Median progression free survival (PFS), duration of response (DOR), time to progression (TTP) and overall survival (OS) have not yet been reached after a median follow-up of 10.3 months; results will be presented at a future medical congress when updated data from an expanded cohort are available. A larger randomised Phase III study in untreated locally advanced or metastatic HCC, IMbrave150, evaluating the combination of TECENTRIQ and Avastin versus the standard of care sorafenib, is underway and recruiting patients.

In early stage bladder cancer, results from an interim analysis of a Phase II investigator-initiated study (ABACUS) evaluating neoadjuvant TECENTRIQ monotherapy in 68 evaluable patients with muscle invasive disease will also be presented. Topline results demonstrated a clinically meaningful pathological complete response (pCR) rate of 18 / 62 (29%). Of the pCR patients, 17% had pT3/4 disease at baseline. Treatment-related Grade 3-4 adverse events occurred in 12% of patients while Grade 3-4 surgical complications occurred in 31% of patients. The trial aims to test the efficacy of preoperative TECENTRIQ and includes extensive biomarker work on samples from these patients.

The results of the three studies will be presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on Sunday 3 June 2018.

About the IMmotion151 study
IMmotion151 is a Phase III multicentre, randomised, open-label study to evaluate the efficacy and safety of TECENTRIQ and Avastin versus sunitinib in people with inoperable, locally advanced or metastatic renal cell carcinoma (RCC) who have not received prior systemic active or experimental therapy. It enrolled 915 people globally who were randomised 1:1 to receive TECENTRIQ and Avastin, or sunitinib alone.

People in the TECENTRIQ and Avastin arm received TECENTRIQ at a fixed dose of 1200 milligrams (mg) and Avastin at a dose of 15 milligrams per kilogram (mg/kg) via intravenous (IV) infusion every 3 weeks until loss of clinical benefit or unacceptable toxicity. People in the sunitinib arm received sunitinib 50 mg orally, once daily for 4 weeks followed by 2 weeks rest until loss of clinical benefit or unacceptable toxicity.

The co-primary endpoints were PFS, as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in people whose tumours expressed PD-L1 (expression ≥1 percent on immune cells [IC]), and OS in the overall study population (intention-to-treat, ITT). PD-L1 expression was prospectively assessed using an immunohistochemistry (IHC) test (SP142) developed by Roche Tissue Diagnostics. Secondary endpoints included OS in people whose tumours expressed PD-L1, PFS as determined by an Independent Review Facility (IRF) according to RECIST v1.1, investigator-assessed objective response rate (ORR) and duration of response (DOR), change from baseline in symptom interference and symptom severity as determined by M.D. Anderson Symptom Inventory (MDASI), and change from baseline in health-related quality of life as determined by European Quality of Life 5-Dimension (EQ-5D) Scores. PROs were evaluated as secondary and exploratory endpoints to document patient perspective on overall clinical benefit for each treatment.

About the Phase Ib study in HCC (NCT02715531)
This Phase Ib study evaluates the safety and clinical activity of the combination of TECENTRIQ and Avastin in people with untreated advanced, unresectable or metastatic HCC. Patients received TECENTRIQ (1200 mg) + Avastin (15 mg/kg) IV every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary objective was to assess the safety and tolerability as well as the efficacy of the combination. The primary efficacy endpoint is investigator-assessed objective response rate (ORR). Secondary efficacy endpoints include progression-free survival (PFS), duration of response (DOR) and time to progression (TTP) per RECIST v1.1; as well as overall survival (OS).

About IMbrave150
IMbrave150 is a Phase III, multicentre, randomised open-label study randomising approximately 480 patients with untreated advanced, unresectable or metastatic hepatocellular carcinoma 2:1 to receive TECENTRIQ in combination with Avastin or sorafenib. TECENTRIQ will be administered by IV, 1200mg on day 1 of each 21 day cycle and Avastin will be administered by IV, 15mg/kg on day 1 of each 21 day cycle. Sorafenib will be administered by mouth, 400mg twice per day, on days 1-21 of each 21 day cycle. Patients will receive the combination and the control arm until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Co-primary endpoints are overall survival and investigator-assessed objective response rate. Secondary endpoints include progression free survival (PFS), time to progression (TTP), duration of response (DOR) and independent review facility (IRF) assessed responses.

About the ABACUS study
ABACUS is an investigator-initiated, open-label, international, multicentre, phase II trial for patients with histologically confirmed (T2-T4a) transitional cell carcinoma of the bladder. The trial aims to test the efficacy of preoperative TECENTRIQ and includes extensive biomarker work on samples from these patients. Patients received two 3-weekly cycles of TECENTRIQ prior to cystectomy. Following cystectomy, patients were followed up for safety, survival, and disease data. Co-primary endpoints are (1) efficacy of atezolizumab prior to cystectomy assessed as pathological complete response rate and (2) immune parameters. Secondary endpoints include safety and efficacy based on anti-tumour effect by radiological response.

About TECENTRIQ (atezolizumab)
TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the activation of T cells. TECENTRIQ has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

TECENTRIQ is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy.

About the TECENTRIQ (atezolizumab) and Avastin (bevacizumab) combination
There is a strong scientific rationale to support combining TECENTRIQ and Avastin. The TECENTRIQ and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers. Avastin, in addition to its established anti-angiogenic effects, may further enhance TECENTRIQ’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About renal cell carcinoma
Kidney cancer remains one of the most common cancers in the world, accounting for over 140,000 deaths worldwide each year,1 with renal cell carcinoma (RCC) accounting for approximately 90% of all cases.2 Over 300,000 people are diagnosed with RCC every year and currently only about 1 in 10 people are alive beyond 5 years following diagnosis of metastatic disease.3

RCC occurs when abnormal cells develop in the tissue of the kidneys, specifically in the small tubes (also known as tubules) where our blood is filtered.4 Typically, RCC is a single tumour in one kidney but, in rare cases, there can be multiple tumours, which can occur in one or both kidneys.5

Despite recent progress in the field of kidney cancer, treatment options for people with the disease remains limited.

About hepatocellular carcinoma
HCC is the most common primary malignancy of the liver and has a very high fatality rate.6 Globally, it’s the fifth most common cancer in men and the seventh most common cancer among women, with over half a million new cases diagnosed annually.6 HCC develops predominantly in those patients with cirrhosis due to chronic hepatitis B or C,6 and typically presents at an advanced stage where there are limited treatment options.7

About urothelial carcinoma
Bladder cancer is the ninth most common cancer worldwide, with 430,000 new cases diagnosed in 2012, and it results in approximately 165,000 deaths globally each year. Men are three times more likely to suffer from bladder cancer, compared with women,8 and the disease is three times more common in developed countries than in less developed countries.9 There are three types of bladder cancer: transitional cell carcinoma (which begins in cells in the innermost tissue layer), squamous cell carcinoma (which begins in squamous cells) and adenocarcinoma (which begins in glandular cells in the lining of the bladder). Most cancers that form in the bladder are transitional cell carcinomas.10

On June 1, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that long-term phase 1 safety and efficacy data for DS-8201, an investigational HER2-targeting antibody drug conjugate (ADC), in 241 heavily pretreated patients with HER2-expressing breast, gastric and other solid cancers who received recommended expansion doses of 5.4 mg/kg or 6.4 mg/kg, will be presented today during an Oral Abstract Session at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (Abstract 2501; 2:57 – 3:09 PM CDT) (Press release, Daiichi Sankyo, JUN 1, 2018, View Source [SID1234527018]).

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Updated preliminary results in a subgroup analysis of 34 patients with heavily pretreated HER2-low-expressing metastatic breast cancer (defined as IHC 2+/ISH- or IHC 1+/ISH- tumors) showed that DS-8201 demonstrated a confirmed overall response rate of 50.0 percent (17/34 patients) and a disease control rate of 85.3 percent (29/34 patients). Preliminary estimates of median duration of response have reached 11 months (95 percent CI: NA) and median progression-free survival has reached 12.9 months (95 percent CI: NA). A total of 14 patients (41.2 percent) were continuing to receive treatment at the time of data cutoff, which was April 18, 2018.

"HER2-targeted treatments historically have not been effective in treating metastatic breast cancer with low levels of HER2 expression," said Hiroji Iwata, MD, PhD, Vice Director and Chief of Breast Oncology at Aichi Cancer Center Hospital, Nagoya, Japan. "While these results of DS-8201 in the HER2-low-expressing subgroup need to be further confirmed in a larger clinical setting, the preliminary data are intriguing in that we may need to begin rethinking how we approach HER2 as a cell surface target for precision medicine treatment in metastatic breast cancer."

In an updated preliminary subgroup analysis in 99 efficacy evaluable patients with HER2-positive metastatic breast cancer pretreated with ado-trastuzumab emtansine (T-DM1) (as well as trastuzumab and pertuzumab in the majority of cases), DS-8201 demonstrated a confirmed overall response rate of 54.5 percent (54/99 patients) and a disease control rate of 93.9 percent (93/99 patients). Median duration of response and median progression-free survival have not yet been reached. Out of 111 patients with HER2-positive metastatic breast cancer who received at least one dose of DS-8201, 65 (55.1 percent) were continuing to receive treatment at the time of data cut off.

Updated overall safety data across all subgroups of the phase 1 study were reported. The most common adverse events (>30 percent, any Grade), included nausea (68.9 percent), decreased appetite (55.6 percent), alopecia (36.1 percent), vomiting (34.9 percent) and anemia (32.0 percent). Grade 3 adverse events occurring in ≥10 percent of patients included decreased neutrophil count (15.4 percent), anemia (14.9 percent), decreased white blood cell count (12.4 percent) and decreased platelet count (10.4 percent). Twenty-three patients (9.5 percent) discontinued treatment due to adverse events, which included ten (10) Grade 5 adverse events: pneumonitis (4), disease progression (2), interstitial lung disease (ILD) (1), ileus (1), pneumonia aspiration (1) and pneumonia (1). All reported or suspected cases of ILD or pneumonitis currently are under review by an independent ILD adjudication committee.

"These updated results further support our broad and comprehensive development program underway exploring the potential of DS-8201 in HER2-low-expressing breast cancer, which represents about half of all breast cancers, as well as in HER2-positive metastatic breast cancer, where unmet treatment needs remain," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "Our pivotal phase 2 trial in HER2-positive metastatic breast cancer is underway, and we are planning phase 3 trials in HER2-low-expressing and HER2-positive metastatic breast cancer in order to determine whether the smart delivery of chemotherapy with DS-8201 may be an effective treatment option against breast tumors that express varying levels of HER2 as a cell surface antigen. A similar biological paradigm is being tested in our other ongoing phase 2 studies of DS-8201 in gastric and colorectal cancer."

HER2-Expressing Gastric Cancer and Other Solid Cancer Subgroup Analyses

Updated preliminary results of two additional subgroup analyses were reported in addition to the two breast cancer subgroups. In the subgroup of 44 patients with HER2-expressing (defined as IHC 3+ or IHC 2+/

ISH-) gastric cancer or gastroesophageal junction adenocarcinoma previously treated with trastuzumab and chemotherapy, DS-8201 demonstrated a confirmed overall response rate of 43.2 percent (19/44 patients) and a disease control rate of 79.5 percent (35/44 patients). Preliminary estimates of median duration of response has reached 7.0 months (95 percent CI: NA) and median progression-free survival has reached 5.6 months (95 percent CI: 3.0, 8.3).

In an updated preliminaryanalysis in 31 evaluable patients with other HER2-expressing solid tumors such as colorectal and non-small cell lung cancer, DS-8201 demonstrated a confirmed overall response rate of 38.7 percent (12/31 patients) and a disease control rate of 83.9 percent (26/31 patients). Preliminary estimates of median duration of response has reached 12.9 months (95 percent CI: 2.8, 12.9) and median progression-free survival has reached 12.1 months (95% CI: 2.7, 14.1).

Unmet Need in HER2-Expressing Breast and Gastric Cancer

About one in five breast and gastric cancers overexpress HER2, a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells, which is associated with aggressive disease.1,2 To be considered HER2-positive, tumor cancer cells are usually tested by one of two methods: immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH).1,3 IHC test results are reported as: 0, IHC 1+, IHC 2+ or IHC 3+.1,3 A finding of IHC 3+ is considered HER2-positive.1,3 A finding of IHC 2+ is borderline and typically is confirmed by a positive FISH test.1,3

Several unmet needs remain today in HER2-expressing metastatic breast cancer. Many HER2-positive tumors advance to the point where no currently approved HER2-targeting treatment continues to control the disease, and there is no current standard of care for HER2-positive tumors after treatment with trastuzumab, pertuzumab and T-DM1.4 Additionally, there are no anti-HER2 therapies indicated for HER2 low-expressing tumors (IHC 2+/FISH- or IHC 1+).

HER2-expressing gastric cancer also is an area of unmet medical need as advances in the treatment of the disease have been limited, largely due to its genetic complexity and heterogeneity.5 Currently, there are no approved HER2-targeting therapy options for patients with HER2-positive advanced gastric cancer after treatment with trastuzumab.

About the DS-8201 Phase 1 Study

The open-label, two-part phase 1 study is currently evaluating DS-8201 in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation phase of the study was to assess the safety and tolerability of DS-8201 and determine the maximum tolerated dose. Data from this part of the study were published in the Lancet Oncology.6

In the dose expansion part of the phase 1 study, DS-8201 is given to patients with HER2-positive advanced or metastatic breast cancer and gastric cancer, HER2-low-expressing breast cancer and other HER2-expressing or mutant solid tumors. Patient enrollment in the two breast cancer cohorts and the HER2-expressing solid tumors cohort is ongoing in the U.S. and Japan. For more information about the study, please visit ClinicalTrials.gov.

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 a smart chemotherapy 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 (FDA). DS-8201 has also been granted SAKIGAKE Designation by the Japan Ministry of Health, Labour and Welfare (MHLW) 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.