On June 4, 2019 Sierra Oncology, Inc. (SRRA), a late-stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported that it has obtained regulatory clarity with the U.S. Food and Drug Administration (FDA) concerning the design of a Phase 3 clinical trial for momelotinib intended to support potential registration of this differentiated drug candidate for the treatment of previously JAK inhibitor treated myelofibrosis patients (Press release, Sierra Oncology, JUN 4, 2019, View Source [SID1234536864]). Following receipt of this clarity, Sierra also announced the design of the MOMENTUM Phase 3 clinical trial in myelofibrosis, planned for launch in Q4 2019.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We have held productive discussions with regulators in the US and EU, presenting a holistic analysis of momelotinib’s compelling array of positive efficacy and safety data observed in the two previously completed SIMPLIFY Phase 3 clinical studies, along with our strategy to conduct an additional Phase 3 trial intended to support momelotinib’s potential registration," said Dr. Nick Glover, President and CEO of Sierra Oncology. "We have been exceedingly pleased with the collaborative nature of these discussions which have culminated in alignment on the path to potential registration for momelotinib. Moreover, we have received constructive input that ensures that the design of the MOMENTUM Phase 3 study has the potential to generate compelling and persuasive clinical data capable of satisfying regulatory requirements."

"Momelotinib has consistently demonstrated clinically relevant benefits on the three hallmarks of myelofibrosis: symptoms, anemia and spleen enlargement," noted Dr. Srdan Verstovsek, MD, PhD, Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston, Texas. "I have been involved in the development of momelotinib for many years, and I am very pleased to be named Chief Investigator of the MOMENTUM Phase 3 study. In my opinion, a good proportion of myelofibrosis patients in the second line setting would be candidates for momelotinib treatment due to its potential ability to improve both quality of life and anemia in a significant number of patients. As a myelofibrosis clinician, I can attest that we desperately need more treatment options that offer an array of distinct benefits for our patients. I look forward to momelotinib potentially becoming an important addition to the armamentarium in the treatment of myelofibrosis."

"We have designed MOMENTUM in order to generate highly persuasive clinical data with the potential to convincingly demonstrate momelotinib’s meaningful benefits on symptoms, anemia and spleen in the population of patients previously treated with a JAK inhibitor, as supplemented by both top-line and post hoc analyses of the prior SIMPLIFY Phase 3 datasets," said Dr. Barbara Klencke, Chief Development Officer, of Sierra Oncology. "We have outlined a robust, tractable study that we plan to launch in Q4 2019 and that we anticipate will yield top-line clinical data in Q4 2021."

About MOMENTUM Phase 3 Clinical Trial:
A Randomized, Double-Blind, Phase 3 Study to Evaluate the Activity of Momelotinib (MMB) versus Danazol (DAN) in Symptomatic, Anemic Subjects with Primary Myelofibrosis (PMF), Post-Polycythemia Vera (PV) Myelofibrosis, or Post Essential Thrombocythemia (ET) Myelofibrosis who were Previously Treated with JAK Inhibitor Therapy.

Sierra plans to launch the MOMENTUM Phase 3 clinical trial in Q4 2019. The randomized double-blind trial is designed to enroll 180 myelofibrosis patients who are symptomatic and anemic and have been treated previously with a JAK inhibitor. Patients will be randomized 2:1 to receive either momelotinib or danazol. Danazol has been selected as an appropriate treatment comparator given its use to ameliorate anemia in myelofibrosis patients, as recommended by NCCN and ESMO (Free ESMO Whitepaper) guidelines. After 24 weeks of treatment, patients on danazol will be allowed to crossover to receive momelotinib.

The Primary Endpoint of the trial is the Total Symptom Score (TSS) response rate of momelotinib compared to danazol at Week 24 (99% power; p-value < 0.05). Secondary and exploratory endpoints include:

Transfusion Independence (TI) rate at Week 24 (key secondary: > 90% powered; p-value < 0.05),
Splenic response rate (SRR) at Week 24 (> 90% powered; p-value < 0.05),
Duration of TSS response to Week 48,
Other measures of anemia benefit, including Transfusion Dependence response rate and various measures of cumulative transfusion burden,
Patient Reported Outcome measures of fatigue and physical function.
About Dr. Srdan Verstovsek, Chief Investigator of the MOMENTUM Phase 3 trial:
Dr. Srdan Verstovsek is Chief, Section for Myeloproliferative Neoplasms, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston. Dr. Verstovsek is a world-renowned physician-scientist, and a leading global authority on the treatment of myelofibrosis. His clinical and translational research is focused on understanding the biology of and developing new therapies for myeloproliferative neoplasms (MPNs). He has been Principal investigator for more than 50 clinical trials testing novel therapies for patients with MPNs, and has published more than 400 peer-reviewed manuscripts. He is the recipient of numerous awards including the Celgene 2010 Young Investigator Award, 7th Annual Irwin H. Krakoff Award for Excellence in Clinical and the Distinguished Lecturer Award from the Society of Hematologic Oncology and the Otis W. and Pearl L. Walters Faculty Achievement Award in Clinical Research by MD Anderson Cancer Center. He was made a Member of The American Society for Clinical Investigation in recognition of his contributions as a physician-scientist.

Momelotinib Analyst & Investor Conference Call
The company will be hosting an Analyst and Investor conference call at 6:00am ET on Wednesday, June 5, 2019, to discuss next steps for momelotinib.

Domestic (Toll Free- US): 1-800-239-9838
International (Toll): 1-323-794-2551
Conference ID: 8101895
Webcast Link: www.sierraoncology.com
Direct Link: View Source

Event registration and webcast information are available through the Sierra Oncology website at www.sierraoncology.com. An archive of the presentation will be accessible after the event through the Sierra Oncology website.

About Momelotinib
Momelotinib, Sierra’s lead drug candidate, is a potent, selective and orally-bioavailable JAK1, JAK2 & ACVR1 inhibitor with a differentiated therapeutic profile in myelofibrosis encompassing robust constitutional symptom improvements, a range of meaningful anemia benefits, including eliminating or reducing the need for frequent blood transfusions, and comparable spleen control to ruxolitinib. More than 1,200 subjects have received momelotinib since clinical studies began in 2009, including more than 800 subjects treated for myelofibrosis. Momelotinib is covered by patents anticipated to provide potential exclusivity to 2040 in the U.S.

On June 4, 2019 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Type II variation to the European Medicines Agency (EMA) seeking approval of ERLEADA (apalutamide) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), regardless of extent of disease or prior docetaxel treatment history (Press release, Johnson & Johnson, JUN 4, 2019, View Source [SID1234536881]). The submission is based on findings from the Phase 3 TITAN study which were presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and simultaneously published online in The New England Journal of Medicine.1,2

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The submission to the EMA follows the submission of supplemental registration dossiers to the U.S. Food and Drug Administration (FDA) on 29th April 2019 and to the Japanese Ministry of Health, Labour and Welfare (MHLW) on 31st May 2019 seeking approval of a new indication for apalutamide for the treatment of patients with mHSPC.3,4

"Today’s application seeking to expand the approval of apalutamide for the treatment of patients with mHSPC marks an important step in our continued focus and commitment to bring innovative medicines forward in the treatment of prostate cancer," said Dr. Joaquín Casariego, Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag S.A. "We look forward to working with the EMA to expand access to this next-generation androgen receptor inhibitor for those patients who may benefit from this treatment in the future."

Results from the Phase 3 TITAN study showed patients with mHSPC, treated with apalutamide plus androgen deprivation therapy (ADT) significantly extended overall survival (OS) compared to placebo plus ADT with a 33 percent reduction in the risk of death (HR=0.67; 95% CI, 0.51-0.89; P=0.0053).2 In both study arms, median OS was not reached.2 Apalutamide plus ADT also significantly improved rPFS compared to placebo plus ADT with a 52 percent reduction in risk of radiographic progression or death compared to placebo plus ADT (HR=0.48; 95% CI, 0.39-0.60; P<0.0001).1 The median rPFS was 22.1 months for placebo plus ADT and not reached for apalutamide plus ADT.2 The two-year OS rates, after a median follow up of 22.7 months, were 82 percent for apalutamide plus ADT compared to 74 percent for placebo plus ADT.2

Adverse events (AEs) were generally consistent with the known apalutamide safety profile. The incidence of Grade 3/4 AEs for apalutamide plus ADT, versus placebo plus ADT were similar (42 percent vs 41 percent).2 The most common Grade ≥3 AEs for apalutamide plus ADT versus placebo plus ADT were hypertension (8.4 percent vs. 9.1 percent) and skin rash (6.3 percent vs. 0.6 percent).2 Additional reported Grade ≥3 AEs for apalutamide plus ADT versus placebo plus ADT were back pain (2.3 percent vs. 2.7 percent), blood alkaline phosphatase increased (0.4 percent vs. 2.5 percent) and anemia (1.7 percent vs. 3.2 percent).2 Treatment discontinuation due to AEs was 8 percent in the apalutamide arm compared to 5 percent in the placebo arm.1 Rash of any grade was more common among patients treated with apalutamide plus ADT, versus placebo plus ADT (27 percent vs 9 percent, respectively).2

In Europe, apalutamide is currently approved for use in adults with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease.5 In the U.S. apalutamide is indicated for the treatment of nmCRPC.6

ENDS

About the TITAN Study1,2

TITAN is a Phase 3 randomised, placebo-controlled, double-blind study in men with mHSPC regardless of extent of disease or prior docetaxel treatment history. The study included 1,052 patients in intention-to-treat (ITT) population in 23 countries across 260 sites in North America, Latin America, South America, Europe and Asia Pacific. Patients with mHSPC were randomised 1:1 and received either apalutamide (240 mg) plus continuous androgen deprivation therapy (ADT) (n=525), or placebo plus ADT (n=527). The recruitment period for the study spanned from December 2015 to July 2017. The study included mHSPC patients with both low- and high-volume disease, those who were newly diagnosed, or those who had received prior definitive local therapy or prior treatment with up to six cycles of docetaxel or up to six months of ADT for mHSPC. Participants were treated until disease progression or the occurrence of unacceptable treatment-related toxicity. An independent data-monitoring committee was commissioned by the sponsor to monitor safety and efficacy before unblinding and make study conduct recommendations. Dual primary endpoints of the study were OS and rPFS. Secondary endpoints included time to cytotoxic chemotherapy, time to pain progression, time to chronic opioid use and time to skeletal-related event. Exploratory endpoints included time to PSA progression, time to second progression-free survival and time to symptomatic progression. For additional study information, visit ClinicalTrials.gov.

About ERLEADA

ERLEADA (apalutamide) is an androgen receptor (AR) inhibitor indicated for use in Europe for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease.5 In the U.S. apalutamide is indicated for the treatment of nmCRPC.6

About Metastatic Hormone-Sensitive Prostate Cancer

Metastatic hormone-sensitive prostate cancer (mHSPC), also referred to as metastatic castration sensitive prostate cancer (mCSPC) refers to prostate cancer that still responds to androgen deprivation therapy (ADT) and has spread to other parts of the body.7 Patients with mHSPC tend to have a poor prognosis, with a median OS of less than five years, underscoring the need for new treatment options.8,9,10

On June 4, 2019 VBL Therapeutics (Nasdaq: VBLT), reported that Dr. Dror Harats, CEO will deliver a company presentation today at the 2019 BIO International Convention in Philadelphia (Press release, VBL Therapeutics, JUN 4, 2019, View Source [SID1234536865]). The presentation will include a discussion on the recent VB-111 progress, including data presented earlier this week at the 2019 ASCO (Free ASCO Whitepaper) Annual Meeting. The presentation will be also available to the investor audience by webcast.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

2019 BIO International Convention – Presentation Details

Date: June 4, 2019
Time: 3:30 pm EDT
Presentation Room: Theater 2
Location: Philadelphia Convention Center
Webcast: 2019 BIO International Convention Webcast

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 Amgen (NASDAQ: AMGN) reported the first clinical results from a Phase 1 study evaluating investigational AMG 510, the first KRASG12C inhibitor to reach the clinical stage (Press release, Amgen, JUN 3, 2019, View Source;p=RssLanding&cat=news&id=2400393 [SID1234536796]). In the trial, there were no dose-limiting toxicities at tested dose levels. AMG 510 showed anti-tumor activity when administered as a monotherapy in patients with locally-advanced or metastatic KRASG12C mutant solid tumors. These data are being presented during an oral session at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"KRAS has been a target of active exploration in cancer research since it was identified as one of the first oncogenes more than 30 years ago, but it remained undruggable due to a lack of traditional small molecule binding pockets on the protein. AMG 510 seeks to crack the KRAS code by exploiting a previously hidden groove on the protein surface," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "By irreversibly binding to cysteine 12 on the mutated KRAS protein, AMG 510 is designed to lock it into an inactive state. With high selectivity for KRASG12C, we believe investigational AMG 510 has high potential as both a monotherapy and in combination with other targeted and immune therapies."

The Phase 1, first-in-human, open-label multicenter study enrolled 35 patients with various tumor types (14 non-small cell lung cancer [NSCLC], 19 colorectal cancer [CRC] and two other). Eligible patients were heavily pretreated with at least two or more prior lines of treatment, consistent with their tumor type and stage of disease. The primary endpoint is safety, and key secondary endpoints include pharmacokinetics, objective response rate (assessed every six weeks), duration of response and progression-free survival. Patients were enrolled in four dose cohorts – 180 mg, 360 mg, 720 mg and 960 mg, taken orally once a day.

Five out of 10 evaluable patients with NSCLC experienced a partial response (PR), and another four had stable disease (SD), for a disease control rate (DCR) of 90 percent (9/10).1 All five patients with response to therapy had a treatment duration of 7.3-27.4 weeks at data cutoff and remain active on treatment. One patient with PR improved further to a complete response of the target lesions at week 18, post data cutoff.

In addition, 13 of 18 evaluable patients with CRC achieved SD, with the majority of CRC patients treated at the first two dose levels. Twenty-six patients remain on study and nine have discontinued.

Treatment-related adverse events (AEs) were primarily grade 1 events (approximately 68 percent). Two grade 3 treatment-related AEs were reported (anemia and diarrhea). No grade 4 treatment-related AEs and no serious treatment-related AEs were reported. Enrollment into dose expansion is underway.

"While there’s been significant progress in treating solid tumor cancers overall with targeted therapies, patients with the KRASG12C mutation have not benefited from these advances," said Marwan G. Fakih, M.D., clinical study investigator and co-director of the Gastrointestinal Cancer Program, City of Hope, Duarte, Calif. "In this early Phase 1 trial, investigational AMG 510 showed encouraging anti-tumor activity. We look forward to further investigating AMG 510 with the goal of closing the treatment gap for patients with this type of mutation."

Amgen Webcast Investor Meeting
Amgen will host a webcast investor meeting at ASCO (Free ASCO Whitepaper) 2019 on Monday, June 3 at 6:30 p.m. CT. David M. Reese, M.D., executive vice president of Research and Development at Amgen, along with members of Amgen’s clinical development team and clinical investigators, will participate at the investor meeting to discuss Amgen’s oncology program and data presented at ASCO (Free ASCO Whitepaper) 2019. Live audio of the conference call will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen’s business given at certain investor and medical conferences, can be accessed on Amgen’s website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

About KRAS
The subject of more than three decades of research, the RAS gene family are the most frequently mutated oncogenes in human cancers.2,3 Within this family, KRAS is the most prevalent variant and is particularly common in solid tumors.3 A specific mutation known as KRASG12C accounts for approximately 13 percent of non-small cell lung cancers, three to five percent of colorectal cancers and one to two percent of numerous other solid tumors.4 Approximately 30,000 patients are diagnosed each year in the United States with KRASG12C driven cancers.5 Amgen is exploring the potential of KRASG12C inhibition across a broad variety of tumor types.

On June 3, 2019 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported results from a preplanned analysis of immunologic responses in the cohort of patients with triple negative breast cancer (TNBC) from the prospective, randomized, single-blinded, controlled Phase 2b independent investigator-sponsored clinical trial of nelipepimut-S (NPS) +/- trastuzumab (Herceptin) targeting HER2 low-expressing breast cancer patients (Press release, Sellas Life Sciences, JUN 3, 2019, View Source [SID1234536812]). This analysis was presented on June 2, 2019 at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, IL.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Effective adjuvant/maintenance therapy strategies are urgently needed to prevent recurrence or to prolong remission in patients with TNBC after successful frontline standard therapy for early-stage disease. In this setting, immune-directed therapy with NPS, a peptide vaccine targeting HER2, a protein expressed at low levels in TNBC, along with trastuzumab, led to high rates of antigen-specific immunization by both ex vivo and in vivo validated measures, corroborating the immunobiological synergy between these two agents," said Elizabeth A. Mittendorf, MD, PhD, Rob and Karen Hale Distinguished Chair in Surgical Oncology, Director of Research, Breast Surgical Oncology Brigham and Women’s Hospital, Director, Breast Immuno-Oncology Program Dana-Farber/Brigham and Women’s Cancer Center, and the Principal Investigator of the Phase 2b study.

"These ex vivo and in vivo results in TNBC patients, particularly the newly discovered correlation between mounting an immune response and remaining clinically relapse-free over time, provide a solid mechanistic rationale for the previously observed clinically meaningful and statistically significant prolongation in disease-free survival (DFS), and the significant decrease in the frequency of relapses identified by standard clinical follow-up, in favor of NPS plus trastuzumab," said Angelos M. Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS.

"As we continue discussions with potential partners and the U.S. Food and Drug Administration (FDA) on this promising program, we remain excited with these data demonstrated in the TNBC population," added Dr. Stergiou.

The Phase 2b study enrolled patients with HER2-low expressing breast cancer who remained clinically disease-free after completion of frontline standard of care therapy. Patients were selected to harbor node-positive disease and/or TNBC, as well as expressing human leukocyte antigen (HLA) types indicated for NPS administration (A2, A3, A24/26; pertinent to approx. 85% of the global population). Patients were randomized to placebo with granulocyte-macrophage colony-stimulating factor (GM-CSF) (n=139) or NPS with GM-CSF (n=136), while they all received trastuzumab every 3 weeks for one year. The Company previously reported results of the final analysis of efficacy and safety outcomes in the cohort of patients whose tumors did not express hormone receptors, TNBC (n=97). DFS of patients treated with NPS plus trastuzumab (n=53) was 92.6% compared to 70.2% for those treated with trastuzumab alone (n=44) and represented a clinically meaningful and a statistically significant improvement with the combination therapy, p=0.01. This was associated with a statistically significant reduction by 71.9% (p=0.01) in the frequency of clinically detected recurrences in favor of the combination in the TNBC cohort.

Ninety-one of the 97 TNBC patients in this clinical study were analyzed for immune responses (IR) at five timepoints, 51 of whom received the combination therapy. IR were evaluated ex vivo by clonal expansion of antigen NPS-specific cytotoxic T-lymphocytes (CTL) by dextramer-staining/flow cytometry at predefined time points over three years. In vivo IR were assessed by cutaneous delayed type hypersensitivity (DTH) reactions periodically, by measuring the diameter of skin induration (in mm) post intradermal NPS treatment.

NPS plus trastuzumab-treated TNBC patients exhibited increases in CTL frequencies compared with baseline by 1.1-, 1.73-, and 2.86-fold at 18, 24 and 30 months, respectively. The mean CTL frequencies in these patients increased from 29±0.1 per 10-4 at baseline to 112±2.6% at 30 months, a 2.86-fold difference that was highly clinically indicative (p = 0.058), as compared with patients receiving trastuzumab only, whereby CTL frequencies were 20±0.1 per 10-4 at baseline compared with 52±1.6 per 10-4 at 30 months, a 1.6-fold non-significant difference (p=0.70). Three patients in the combination arm recurred (5.9%) as compared with 12 (30%) in the trastuzumab-alone arm. TNBC patients treated with NPS plus trastuzumab whose disease recurred did not mount an IR by ex vivo assessment (absolute CTL frequency change) or by in vivo DTH (no change in skin induration), while non-recurrent patients mounted both vigorous NPS-specific clonal CTL expansion and enhanced in vivo DTH.