On June 1, 2018 Elios Therapeutics, a biopharmaceutical company developing innovative autologous, particle-delivered, dendritic cell cancer vaccines, reported interim data from the ongoing prospective, randomized, double-blind, placebo-controlled Phase IIb clinical trial of the TLPLDC (tumor lysate, particle-loaded, dendritic cell) vaccine in patients with Stage III and IV, resected melanoma will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 4, 2018 in Chicago, Illinois (Abstract # 9525) (Press release, Orbis Health Solutions, JUN 1, 2018, View Source [SID1234529912]).

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The planned interim analysis was conducted after the first 120 patients enrolled in the trial had been randomized and treated for at least 6 months. In the per treatment population, TLPLDC showed a meaningful 32 percent reduction in the relative risk of recurrence (TLPLDC 29.4 percent vs. placebo 43.3 percent, p = 0.07) with a median follow-up of 12.6 months. There was no difference in recurrence in the intent-to-treat population (TLPLDC 56.6 percent, placebo 54.1 percent, p=0.65) with 11.9 months median follow-up. Overall, TLPLDC was safe and well-tolerated. In the study, only 33 percent of participants experienced any adverse event, and 98.6 percent of those were grade 1 and 2 events that included injection site reactions and flu-like symptoms. No serious adverse events were reported.

"The interim data evaluating the TLPLDC vaccine as an adjuvant treatment to prevent melanoma recurrences are very encouraging, suggesting clinical activity and demonstrating an attractive safety profile," said George E. Peoples, M.D., chief medical officer at Elios Therapeutics. "These data, combined with the recently reported results of our open label Phase II study demonstrating the synergistic effects of the TLPLDC vaccine in combination with checkpoint inhibitors, suggest a strong rationale for further clinical development in a Phase III program."

Detailed results from the ongoing Phase IIb study evaluating TLPLDC will be presented on Monday, June 4, 2018:

Abstract 9525 (Poster #352): Interim analysis of a prospective, randomized, double-blind, placebo-controlled, Phase IIb trial of the TLPLDC vaccine to prevent recurrence in resected Stage III or IV melanoma patients
Presenter: John W. Myers, M.D., San Antonio Military Medical Center, Houston, TX
Data/Time: Monday, June 4, 2018 from 1:15 PM – 4:45 PM CDT
Session: Melanoma/Skin Cancers Poster Session – Hall A
About the Study Design
Elios Therapeutics is conducting a prospective, randomized, double-blind, placebo-controlled Phase IIb trial to evaluate the safety and efficacy of TLPLDC in patients with resected Stage III and IV melanoma. The primary endpoint is 2 year disease-free survival (DFS).

In the study, 120 participants were randomized (2:1) to receive either TLPLDC vaccine or placebo to prevent recurrence. TLPLDC or placebo vaccines were initiated within 3 months of completion of standard of care (SoC) therapies and were given at 0, 1, 2, 6, 12, and 18 months. Study participants were followed for recurrence per SoC. The interim analysis was pre-specified at 6 months from randomization of the 120th study participant. Survival analysis was performed on the intent-to-treat and per treatment populations. The latter excludes early recurrences during the primary vaccine series (up to 6 months).

About TLPLDC
The TLPLDC (tumor lysate, particle-loaded, dendritic cell) vaccine is an autologous, personalized, therapeutic cancer vaccine designed to stimulate the immune system to recognize tumor cells and fight a patient’s specific cancer. TLPLDC is made from a patient’s own tumor and dendritic cells – the most potent antigen-presenting cells in the body. Once TLPLDC is injected, the tumor lysate-loaded dendritic cells present the tumor antigens to the immune system, stimulating the induction of tumor-specific, activated T cells that are able to find and destroy tumor cells that may remain in the body. TLPLDC is currently being studied as a monotherapy and in combination with SoC checkpoint inhibitor therapy in a Phase IIb clinical trial for the treatment of late-stage melanoma at leading academic cancer centers in the United States.

On June 1, 2018 SELLAS Life Sciences Group Inc., (Nasdaq:SLS) (SELLAS) reported that the sponsor-principal investigator, after taking into account that key clinical development objectives were met as well as other regulatory considerations, and in agreement with SELLAS, determined to terminate early the Phase 2b independent investigator-sponsored clinical trial (IST) of trastuzumab (Herceptin) +/- nelipepimut-S (NeuVax) in HER2 1+/2+ breast cancer patients (Press release, Sellas Life Sciences, JUN 1, 2018, View Source [SID1234527360]). In this Phase 2b study, Herceptin was provided under a Clinical Trial Supply Agreement by Genentech, Inc. The decision to early terminate this Phase 2b study was based in part on the previously announced recommendation of the independent Data Safety Monitoring Board (DSMB) to further advance the development of the NeuVax + Herceptin combination for the triple negative breast cancer (TNBC) patient population. Data from the Phase 2b has been submitted for presentation at a major medical conference that will take place during the second half of 2018.

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"We wish to thank our patients and their families for their participation in this trial. Based on data demonstrating that this combination therapy has the potential to become an important therapeutic option for TNBC patients facing a life-threatening disease and for whom current options in the adjuvant setting are extremely limited, we have determined, in consensus with SELLAS, to close out the current study," stated COL (ret) George E. Peoples, MD, FACS, Founder and Director of Cancer Insight, LLC and study Principal Investigator. "We look forward to supporting SELLAS’ interactions and discussions with regulatory bodies."

SELLAS conducted this week two advisory meetings with global experts in regulatory affairs and breast cancer clinical development in order to determine the optimal path for further development of the NeuVax + Herceptin combination in TNBC in a pivotal setting and engagement with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).

As previously announced, a pre-specified interim analysis of safety and efficacy conducted by the DSMB, demonstrated a clinically meaningful and statistically significant difference between the TNBC cohort of patients and the control arm with a hazard ratio of 0.26, p-value = 0.023, in favor of the NeuVax + Herceptin combination compared to Herceptin alone. The analysis also showed an adverse event profile with no notable differences between treatment arms and no additional cardiotoxicity in the NeuVax + Herceptin arm. Based on these positive results, the DSMB recommended to expeditiously seek regulatory guidance from the FDA for further development of the combination of NeuVax + Herceptin in TNBC, a population with a large unmet medical need.

"We agree with Dr. Peoples’ decision to close this Phase 2b study earlier than planned and it is a priority to advance the development program for NeuVax + Herceptin in TNBC. Indeed, we have initiated the necessary steps for prompt engagement with the regulatory authorities for their guidance on the expeditious development of this combination therapy, as exemplified by the clinical and regulatory advisory board meetings we just conducted during this year’s ASCO (Free ASCO Whitepaper) meeting," said Nicholas J. Sarlis, MD, PhD, FACP, Executive Vice President and Chief Medical Officer of SELLAS.

Providing their impressions from the discussion of the Phase 2b study data during the Clinical Advisory Board meeting at the ASCO (Free ASCO Whitepaper) conference, Debu Tripathy, MD, Professor and Chairman, Department of Breast Medical Oncology, The University of Texas – MD Anderson Cancer Center, mentioned that "in early stage TNBC the benefit of chemotherapy in the adjuvant setting is incomplete and leaves room for improvement. Further, to date, targeted therapies have not proven effective for TNBC. Targeting HER2 as an immune therapy target with the Herceptin plus NeuVax combination in HER2 1+/2+ TNBC makes sense biologically, especially considering the baseline presence of activated cellular immunity components in most patients with this tumor type," while Prof. Dr. med. Volkmar Müller, MD, PhD, Professor and Deputy Director, Department of Gynecology, University Clinic of Hamburg-Eppendorf, Germany commented, "The data from the Phase 2b study of Herceptin + NeuVax are promising in the TNBC cohort. SELLAS’ decision to pursue clinical and regulatory strategies with this combination in TNBC based on the current findings is justified, due to the high unmet need, low number of competing trials in the maintenance/adjuvant setting and feasibility of a pivotal Phase 3 study design whereby a relapse-based endpoint could be reached with confidence." Neither Prof. Tripathy nor Prof. Dr. med. Müller participated in the NeuVax + Herceptin Phase 2b study.

SELLAS also announced that it has appointed Jeffrey S. Weber, MD, PhD, as Chairman of its SAB. In his new role, together with the other members of the Company’s SAB, Dr. Weber will strengthen the Company’s capacities to drive, position and prioritize pipeline development with key focus on two assets, galinpepimut-S and nelipepimut-S (NeuVaxTM).

"We are very proud to expand Jeff’s role on the Company’s SAB. Jeff is a leading expert in cancer immunotherapeutics, with broad advisory experience to biopharmaceutical companies in the immuno-oncology field and has a proven leadership track in academic centers. His insights and ability to coordinate and collaborate with our SAB members and our scientific and clinical leadership will help us to more efficiently develop our peptide immunotherapeutic vaccines candidates," said Dr. Sarlis. "Having worked with Jeff as a member of our SAB over the past 2 years, we are delighted to strengthen our collaboration," added Dr. Sarlis.

Dr. Weber currently serves as Co-Director of the Melanoma Program at the New York University (NYU)-Langone Perlmutter Cancer Center and Deputy Director of the Center. Prior to this position, he was Head of the Melanoma Center of Excellence at H. Lee Moffitt Cancer Center. Earlier in his career, Dr. Weber worked as a Senior Investigator in the Surgery Branch of the National Cancer Institute (NCI) at the National Institutes of Health (NIH) and before that served as Chief of Medical Oncology at the University of Southern California (USC)’s Keck School of Medicine. He is a member of the Editorial Boards at Journal of the National Cancer Institute, Clinical Cancer Research, Human Gene Therapy and Journal of Immunotherapy and has served on or chaired numerous NCI study sections. Dr. Weber has published more than 180 articles in the top peer-reviewed journals, including New England Journal of Medicine and Nature Medicine. Dr. Weber was the recipient of the Bob Chandler Courage Award from the USC, of a K24 Mid-Career Mentor Award from NIH, has been recognized as one of the "Best Doctors in America" for over a decade and was the OncLive Giants of Cancer in Melanoma for 2016. He was also the first investigator to demonstrate that PD-1 inhibitors had encouraging activity in resected melanoma patients.

"I am delighted to become the Chairman of the Scientific Advisory Board of SELLAS and honored to work together with my colleagues at the SAB to meaningfully support the company’s quest to change the field by innovative approaches to vaccinate patients using immunogenic peptides for the treatment of cancer," commented Dr. Weber.

Herceptin is a registered trademark of Genentech, Inc. and is not a trademark of SELLAS. The manufacturer of this brand is not affiliated with and does not endorse SELLAS or its products.

On June 1, 2018, bluebird bio, Inc. ("bluebird") presented the investor presentation(Presentation, bluebird bio, JUN 1, 2018, View Source [SID1234527246]).

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On June 1, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported the first data from the ongoing Phase 1 study evaluating single agent AG-881 in advanced glioma and other solid tumors (Press release, Agios Pharmaceuticals, JUN 1, 2018, View Source [SID1234527131]). The data were featured in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. AG-881 is an investigational, oral, selective, potent inhibitor of mutant isocitrate dehydrogenase-1 (IDH1) and IDH2 enzymes, which was designed for enhanced brain penetrance for development in IDH-mutant glioma.

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"IDH mutant glioma is a distinct disease where patients are typically diagnosed in their thirties and forties and endure a deteriorating quality of life from the side effects associated with multiple rounds of surgery, radiation and chemotherapy and ultimately die of their disease," said Ingo Mellinghoff, M.D., Memorial Sloan Kettering Cancer Center, an investigator for the study. "The AG-881 Phase 1 dose-escalation data are encouraging, as they demonstrate a favorable safety profile at lower dose levels and show signals of clinical activity that support further evaluation of the role of inhibiting mutant IDH in low-grade glioma."

"With no curative or approved targeted therapies for low-grade glioma and a poor long-term prognosis, we are committed to exploring the novel mechanism of action of our IDH inhibitors in this indication," said Chris Bowden, M.D., chief medical officer at Agios. "Data from our ivosidenib and AG-881 Phase 1 trials and the ongoing perioperative study, combined with feedback from regulators and the neurology community, will inform our pivotal development plan."

The ongoing Phase 1 dose-escalation trial is assessing the safety and tolerability of AG-881 in IDH1/2 mutant advanced solid tumors, including glioma. As of the March 29, 2018 data cut-off, 93 patients (52 with glioma and 41 with other solid tumors) have been treated with single agent AG-881. Enrollment is complete and 17 glioma patients and 1 non-glioma solid tumor patient remain on treatment. Study design, status and baseline characteristics for the 52 glioma patients are reported below.

Forty-eight percent of patients (n=25) had World Health Organization (WHO) classified Grade 2 tumors, 42% (n=22) had Grade 3 tumors, 8% (n=4) had Grade 4 tumors and 2% (n=1) was unknown.
LOGO

Ninety-two percent of patients (n=48) had an IDH1 mutation and 6% (n=3) had an IDH2 mutation. One patient did not have a biopsy but was confirmed as IDH mutant positive due to 2-HG elevation by magnetic resonance spectroscopy (MRS).

The median age of these patients is 42.5 years (ranging from 16-73 years).

Patients received a median of two prior systemic therapies (ranging from one to six).

Seventy-three percent of patients (n=38) had previously received temozolomide and 58% percent (n=30) had previously received radiotherapy.

Patients received daily doses of AG-881 ranging from 10 mg to 300 mg.

The median treatment duration was seven months (ranging from 0-27 months) for all glioma patients, 12 months (ranging from 1-27 months) for non-enhancing glioma and 3 months (ranging from 0- 27 months) for patients with enhancing disease.
Safety Data

The safety analysis conducted for all 93 treated patients as of the data cut-off demonstrated that AG-881 has a favorable safety profile at dose levels below 100 mg.

The majority of adverse events (AEs) reported by investigators were mild to moderate, with the most common (>33%) being fatigue, nausea, increases in alanine aminotransferase (ALT) and increases in aspartate aminotransferase (AST).

Grade 3 or higher AEs were observed in 33% of all patients (n=31).

Dose limiting toxicities (DLTs) of Grade 2 or higher elevated transaminases occurred in five glioma patients at the higher dose levels (³100 mg) and resolved to Grade £1 with dose modification or discontinuation. There were no treatment-related on-treatment deaths.

A maximum tolerated dose (MTD) was not reached by Bayesian model; the doses chosen for further clinical development were based on safety, pharmacokinetics and pharmacodynamics data.
Efficacy Data

Efficacy data from the 52 glioma patients (23 with non-enhancing and 29 with enhancing disease) as of the data cut-off showed:

One patient with non-enhancing disease and a 1p19q co-deletion had a sustained minor response according to the investigator by Response Assessment in Neuro-Oncology for low grade glioma (RANO-LGG) and remains on treatment.

Seventy-five percent of patients (n=39) had a best response of stable disease, including 20 patients with non-enhancing disease.

Thirty-five percent of patients (n=18, including 13 patients with non-enhancing disease) remained on treatment for ³1 year.
Efficacy data from the 41 patients with non-glioma solid tumors as of the data cut-off showed:

One patient with cholangiocarcinoma had a partial response, 37% of patients (n=15) had stable disease and 44% (n=18) had progressive disease.

The median treatment duration was 2 months (ranging from 0-18 months).
Ongoing Perioperative Study in Glioma

A perioperative ‘window’ trial with ivosidenib and AG-881 (10 mg and 50 mg) in up to 45 IDH1m non-enhancing low-grade glioma patients is ongoing. The goal of the trial is to confirm CNS penetrance and tumor 2-HG suppression of ivosidenib and AG-881 as part of the strategy to finalize pivotal development plans by year-end 2018.

About Glioma

Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low grade glioma) to rapidly progressing (high grade glioma-Glioblastoma Multiforme). Common symptoms include seizures, memory disturbance, sensory impairment and neurologic deficits. The long-term prognosis is poor with a five-year survival rate of 33 percent. Approximately 11,000 low-grade glioma patients are diagnosed annually in the U.S. and EU and approximately 80 percent have an IDH1 mutation.

On June 1, 2018 Immunomedics, Inc., (NASDAQ: IMMU) ("Immunomedics" or the "Company"), a leading biopharmaceutical company in the area of antibody-drug conjugates (ADC), reported that the Company plans to initiate a Phase 2 pivotal TROPHY U-01 study of sacituzumab govitecan, the Company’s lead investigational ADC, as a single agent in patients with locally advanced or metastatic urothelial cancer (mUC) who have relapsed after a platinum-based regimen and/or immune checkpoint inhibitor (CPI) therapy (Press release, Immunomedics, JUN 1, 2018, View Source [SID1234527127]).

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"Urothelial cancer patients who have relapsed after, or are refractory to platinum chemotherapy and the recently approved CPI treatments, have a significant unmet need with few available treatment options," remarked Dr. Rob Iannone, Head of R&D and Chief Medical Officer of Immunomedics. "We are pleased with the FDA guidance on study design and protocol development, which is aligned with the Company’s objective to bring this potential important treatment option to patients expeditiously."

The Phase 2 pivotal study, which is expected to be activated next week, will be a single arm, international, multicenter study that will enroll approximately 100 mUC patients who have received prior platinum-based and CPI treatment. The primary endpoint will be overall response rate, with duration of response, progression-free survival, and overall survival serving as secondary endpoints. Response assessments will be in accordance with RECIST 1.1 and all patients will be centrally reviewed. In addition, the study will also enroll an additional and separate cohort of patients who are cisplatin ineligible and have received prior CPI treatment to evaluate safety and efficacy in an earlier treatment setting.

About Sacituzumab Govitecan

Sacituzumab govitecan, our most advanced product candidate, is a novel, first-in-class antibody-drug conjugate (ADC). It is currently under review by the U.S. Food and Drug Administration for accelerated approval as a treatment of patients with metastatic triple-negative breast cancer who previously received at least two prior therapies for metastatic disease. If approved, sacituzumab govitecan would be the first and only ADC approved for the treatment of metastatic triple negative breast cancer.