On June 2 Nektar Therapeutics (Nasdaq: NKTR) and Bristol-Myers Squibb (NYSE: BMY) reported presentation of preliminary data from the ongoing PIVOT Phase 1/2 Study, which is evaluating the combination of Bristol-Myers Squibb’s Opdivo (nivolumab) with Nektar’s investigational medicine, NKTR-214 (Press release, Bristol-Myers Squibb, JUN 2, 2018, View Source [SID1234527062]). The preliminary results presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) reported safety, efficacy and biomarker data for patients enrolled in the Phase 1 dose-escalation stage of the study and for the first patients consecutively enrolled in select dose expansion cohorts in Phase 2. Data were presented today in an oral presentation (Oral Abstract Session: Developmental Therapeutics—Immunotherapy, Abstract #3006, 5:00 p.m. – 5:15 p.m. CT, Hall B1).

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Enrollment is ongoing in the Phase 2 stage of the PIVOT study in over 400 patients with melanoma, renal cell, urothelial, non-small cell lung and triple negative breast cancers.

Preliminary results from the ongoing PIVOT study presented today showed that pre-specified efficacy criteria were achieved in three tumor types: first-line melanoma, first-line renal cell carcinoma and first-line urothelial cancer. As a result, Nektar and Bristol-Myers Squibb will initiate a Phase 3 registrational trial in first-line advanced melanoma patients in Q3 2018, and pivotal studies are also being designed in renal cell carcinoma and urothelial cancer.

"In the Phase 1 dose-escalation and Phase 2 expansion stages of the PIVOT trial to-date, we’ve observed important responses, including activity in PD-L1 negative patients," said Mary Tagliaferri, M.D., Senior Vice President of Clinical Development and Chief Medical Officer at Nektar Therapeutics. "We look forward to advancing this combination into Phase 3."

The PIVOT study incorporates a Fleming 2-Stage Design, with efficacy targets separately pre-defined for each tumor type using a historical objective response rate (for single-agent checkpoint inhibitor).1 If the efficacy criteria at the recommended Phase 2 dose (RP2D) is met in the first stage (N1) of patients consecutively enrolled or in the second stage (N1 + N2) of patients consecutively enrolled, the combination regimen would be advanced to registrational trials in that tumor type.

Opdivo is a PD-1 immune checkpoint inhibitor designed to overcome immune suppression. NKTR-214 is an investigational immuno-stimulatory therapy designed to expand and activate specific cancer-fighting T cells and natural killer (NK) cells directly in the tumor micro-environment and increase expression of cell-surface PD-1 on these immune cells.

"Researching IL-2 pathway agonism and anti-PD-1 in combination may be a key strategy to more effectively activate an anti-tumor immune response," said Fouad Namouni, M.D., Head of Oncology Development, Bristol-Myers Squibb. "These preliminary results from PIVOT are encouraging, particularly in the PD-L1 negative population, and support our belief that that NKTR-214, a CD122 biased IL2 agonist, in combination with Opdivo can potentially expand the treatment benefits we can bring to patients with cancer."

Highlights from the oral presentation include:

Clinical Efficacy (Response measured per RECIST 1.1 for efficacy-evaluable patients (treated at the recommended Phase 2 dose and with >1 on treatment scan. Response and median time on study calculated from data cut as of May 29, 2018):

Stage IV Metastatic Treatment-Naïve 1L Melanoma Patients (Enrolled Per Fleming 2-Stage Design at RP2D):
Pre-specified efficacy criteria were met for Objective Response Rate (ORR) in Stage 1 (N1=13) with 11/13 (85%) of patients achieving either a partial response (PR) or complete response (CR). Median time on study for 28 patients in Stage 2 (N1+N2) is 4.6 months. Responses were observed in 14/28 (50%) patients (3 CR, 10 PR, 1 uPR). Amongst the 25 patients with known PD-L1 status, ORR in PD-L1 negative patients was 5/12 (42%) and in PD-L1 positive patients was 8/13 (62%). One patient with unknown PD-L1 baseline status experienced a CR.
Stage IV Metastatic Treatment-Naïve 1L Renal Cell Carcinoma Patients (Enrolled Per Fleming 2-Stage Design at RP2D):
Pre-specified efficacy criteria were met for ORR in Stage 1 (N1=11) with 7/11 (64%) of patients achieving a partial response (PR). Median time on study for 26 patients in Stage 2 (N1 + N2) is 5.6 months. Responses were observed in 12/26 (46%) patients (11 PR, 1 uPR). Amongst the 24 patients with known PD-L1 status, The ORR in PD-L1 negative patients was 9/17 (53%) and in PD-L1 positive patients was 2/7 (29%). One of two patients (50%) with unknown PD-L1 baseline status experienced a PR.
Stage IV Metastatic Treatment-Naïve 1L Urothelial Carcinoma (Enrolled Per Fleming 2-Stage Design at RP2D):
Pre-specified efficacy criteria were met for ORR in Stage 1 (N1=10) with 6/10 (60%) of patients achieving either a partial or complete response (2 uCR, 3 PR, 1 uPR). Median time on study for 10 patients in Stage 1 is 3.9 months. The ORR in PD-L1 negative patients was 3/5 (60%) and in PD-L1 positive patients was 3/5 (60%).
Biomarkers and Mechanism of Action:

Data presented show conversion of PD-L1 negative status at baseline to PD-L1 positive status at week 3 in 9/17 patients (53%). Of these previously PD-L1 negative patients, 78% achieved clinical benefit as defined by stable disease, partial response or complete response.
Clinical Safety (Safety database as of May 7, 2018):

A total of 283 patients have been treated at the RP2D. The most common treatment-related adverse events (TRAEs) were grade 1-2 flu-like symptoms (58.7%), rash (44.5%), fatigue (42.0%), and pruritus (31.4%). A total of 40/283 (14.1%) of patients experienced a Grade 3 (G3) or higher TRAE with 6/283 (2.1%) patients discontinuing treatment due to a TRAE. 10/283 (3.5%) of patients experienced a G3 or higher immune-mediated AE. There was one nivolumab-related G5 pneumonitis reported.
A copy of the full data presentation made by Dr. Diab is available on Nektar’s corporate website at View Source

Nektar and Bristol-Myers Squibb entered into a global strategic development and commercialization collaboration for NKTR-214 in February 2018. Under the collaboration, the companies will jointly develop and commercialize NKTR-214 in combination with Bristol-Myers Squibb’s nivolumab and Opdivo plus Yervoy (ipilimumab) in more than 20 indications across 9 tumor types, as well as potential combinations with other anti-cancer agents from either of the respective companies and/or third parties.

About NKTR-214

NKTR-214 preferentially binds to the CD122 receptor on the surface of cancer-fighting immune cells in order to stimulate their proliferation. In clinical and preclinical studies, treatment with NKTR-214 resulted in expansion of these cells and mobilization into the tumor micro-environment.2,3,4 NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

Nektar will webcast an analyst and investor event to review data presented in the oral session and new additional data from the PIVOT study on Saturday, June 2, 2018 at 6:45 p.m. CDT in Chicago, IL. PIVOT clinical investigators attending include Dr. Adi Diab, Assistant Professor, Melanoma Medical Oncology at the University of Texas MD Anderson Cancer Center, Dr. Scott N. Gettinger, Associate Professor, Medical Oncology at the Yale Cancer Center and Dr. Nizar M. Tannir, Professor, Genitourinary Medical Oncology at the University of Texas MD Anderson Cancer Center. Investors and analysts are invited to listen to a live audio webcast of the event, which will be accessible from the home page of the company’s website www.nektar.com. The webcast will also be available for replay for two weeks following the event.

On June 2, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported new efficacy and safety data from the ongoing Phase 1 dose-escalation and expansion study evaluating single agent oral ivosidenib (TIBSOVO; AG-120) in patients with relapsed or refractory acute myeloid leukemia (R/R AML) and an isocitrate dehydrogenase-1 (IDH1) mutation (Press release, Agios Pharmaceuticals, JUN 2, 2018, View Source [SID1234527054]). The data were presented in an oral session at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Ivosidenib is an investigational, first-in-class, oral, targeted inhibitor of the mutant IDH1 enzyme under FDA priority review for IDH1m R/R AML patients with a PDUFA action date of August 21, 2018.

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Agios also announced the publication in the New England Journal of Medicine (NEJM) of data from the ongoing ivosidenib Phase 1 study in patients with advanced hematological malignancies and an IDH1 mutation. The NEJM manuscript, which was published online today and will appear in the June 21, 2018 print issue, provides analyses from the dataset presented at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, with a data cutoff date of May 12, 2017.

"The findings presented at ASCO (Free ASCO Whitepaper) demonstrate that single agent ivosidenib induced durable responses, in some cases with IDH1-mutation clearance, and led to favorable responses compared with historical patient outcomes in a high-risk, molecularly-defined R/R AML population," said Daniel Pollyea, M.D., M.S., study investigator and clinical director of leukemia services at the University of Colorado School of Medicine. "Additional clinical benefits included transfusion independence and, in responding patients, reductions in advanced-grade infections and febrile neutropenia, indicating immune system recovery with functional neutrophils."

"These data provide additional clinical and translational observations beyond the 2017 ASH (Free ASH Whitepaper) presentation, including preliminary data suggesting that R/R AML patients with IDH1-mutation clearance in bone marrow who have achieved CR/CRh have prolonged remission durations and overall survival versus those without IDH1-mutation clearance," said Chris Bowden, M.D., chief medical officer of Agios. "We believe the compelling single-agent efficacy coupled with a tolerable safety profile validate the potential for ivosidenib to be a first-in-class therapy for patients with R/R AML and an IDH1 mutation."

Data Presented at ASCO (Free ASCO Whitepaper)

A total of 258 patients with advanced hematologic malignances and an IDH1 mutation were treated in the Phase 1 study. Enrollment to the study is closed. Complete safety and efficacy data are reported in 179 patients with R/R AML whose ivosidenib starting dose was 500 mg once daily. The median age is 67 (ranging from 18-87), and the median number of prior therapies is two (ranging from one to six). Of these patients, 33% had secondary AML and 24% had prior transplants. The data cutoff for the ASCO (Free ASCO Whitepaper) presentation was November 10, 2017.

Safety Data
As of the data cut-off, a safety analysis conducted for 179 treated R/R AML patients showed that ivosidenib demonstrates a favorable safety profile that is consistent with previously reported data for all 258 patients. The most common adverse events (AEs) of any grade > 25% regardless of causality were diarrhea (33.5%), leukocytosis (31.3%), nausea (31.3%), febrile neutropenia (29.1%), fatigue (28.5%) and electrocardiogram (ECG) QT prolonged (25.7%). Adverse events of interest were the following:

8% reported Grade ≥3 leukocytosis, which was managed with hydroxyurea.
10% reported Grade ≥3 ECG QT prolongation. Ivosidenib dose was reduced in two patients and held in 13 patients (for any grade of ECG QT prolongation).
10.6% reported IDH-differentiation syndrome (IDH-DS) of any grade, which was managed with corticosteroids and diuretics. Six patients had their dose temporarily held, no patients required dose reductions.
No AEs of interest lead to any permanent treatment discontinuations or deaths.
Efficacy Data
Data from 179 R/R AML patients demonstrated an overall response rate (ORR) of 41.9% (75 of 179 patients) and a combined complete remission (CR) and CR with partial hematologic recovery (CRh) rate of 31.8% [95% CI 25.1, 39.2] which is the primary endpoint of the study.

The CR rate was 24% (43 of 179 patients) [95% CI 18.0, 31.0] and the CRh rate was 7.8% (14 of 179 patients). CRh is defined as <5% of blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts (ANC >500/microliter and platelets >50,000/microliter).
Median duration of response was 10.1 months [95% CI 6.5, 22.2] for patients who achieved a CR, 8.2 months [95% CI 5.6, 12.0] for patients who achieved a CR/CRh and 6.5 months [95% CI 5.5, 10.1] for all patients who responded.
Median time to first response was 1.9 months (0.8-4.7) for all patients who responded and median time to CR/CRh was 2.0 months [95% CI 0.9, 5.6].
Transfusion independence, defined as an absence of transfusions for at least 56 consecutive days on treatment, was observed across all response categories.
Of the patients who were transfusion dependent at baseline and achieved a CR, all became independent of platelet transfusions and 88.2% became independent of RBC transfusions during any 56-day post baseline period.
Of the patients who were transfusion dependent at baseline and achieved a CRh, 75% became independent of platelet transfusions and 77.8% became independent of RBC transfusions during any 56-day post baseline period.
Achievement of transfusion independence was also seen among non-CR/CRh responders and non-responders.
Patients who achieved CR and CRh had lower rates of exposure-adjusted febrile neutropenia and Grade ≥3 infections during ivosidenib treatment than patients in other response categories.
Translational Findings
IDH1 mutation clearance, defined as absence of the IDH1 mutation with a sensitivity of 0.02–0.04% (2-4 x10-4), was observed in 23% (11/47) of patients with R/R AML who achieved CR or CRh and had molecular data available, including 28% (10/36) of patients with CR and 1/11 patients with CRh. Preliminary data suggest that R/R AML patients with IDH1-mutation clearance in bone marrow mononuclear cells who have achieved CR/CRh have prolonged remission durations and overall survival versus those without IDH1-mutation clearance.

About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and the median age of diagnosis is 68. The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 27 percent. IDH1 mutations are present in about 6 to 10 percent of AML cases.

On June 2, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported initial data from the ongoing pilot study of NY-ESO SPEAR T-cells in myxoid/round cell liposarcoma (MRCLS). With eight patients treated, the best overall responses include three confirmed partial responses, one unconfirmed partial response, three stable disease, and one recently treated patient awaiting assessment (Press release, Adaptimmune, JUN 2, 2018, View Source;p=RssLanding&cat=news&id=2352862 [SID1234527053]). These data were presented during an oral presentation by Dr. Sandra P. D’Angelo of the Memorial Sloan Kettering Cancer Center at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting.

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GlaxoSmithKline plc (LSE:GSK) (NYSE:GSK) exercised its option to exclusively license the right to research, develop, and commercialize the NY‑ESO SPEAR T-cell therapy program in September 2017. Transition of this program to GSK is ongoing.

"We continue to see responses in patients with advanced MRCLS who have failed previous standard chemotherapy," said Rafael Amado, Adaptimmune’s Chief Medical Officer. "We observe significant proliferation of our SPEAR T‑cells in peripheral blood, and infiltration into metastases that were previously devoid of inflammatory cells. These findings bode well for a broad therapeutic potential of SPEAR T‑cells across multiple solid tumors."

Data Update from the Ongoing NY-ESO MRCLS Study
During an oral presentation on June 2nd entitled, "Pilot Study of NY-ESO-1c259T Cells in Advanced Myxoid/Round Cell Liposarcoma," Dr. D’Angelo presented an update from this ongoing study (data cut-off May 23 2018).

Responses:
Best overall responses include 3 confirmed partial responses, 1 unconfirmed partial response, 3 patients with stable disease, and 1 recently treated patient awaiting assessment
There is an overall trend in tumor burden decrease among the majority of patients
The tumor burden decrease across target lesions ranged from 16.9% to 50%
Three patients have now progressed
Safety: Thus far, data indicate that NY-ESO SPEAR T-cells remain generally well tolerated in this patient population:
There was one event of cytokine release syndrome (CRS) ≥ Grade 3, which was characterized by fever, hypotension, rash, headache, and supraventricular tachycardia. The patient was treated with tociluzumab. The CRS resolved six days post-infusion.
There were four SAEs reported by three patients:
Grade 3 CRS (noted above), which resolved
Two Grade 2 events of CRS, both of which resolved
Grade 2 pleural effusion, which improved with treatment and the patient was subsequently discharged from hospital
Most adverse events were consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or cancer immunotherapies
SPEAR T-cell persistence: Although data are preliminary, there appears to be a correlative trend between SPEAR T-cell persistence and response.
Overview of Study Design

Open-label, non-randomized pilot study evaluating the safety, tolerability, and antitumor activity of NY-ESO SPEAR T-cells in patients with MRCLS
Initially, 10 patients are planned to be enrolled, with potential to enroll an additional 5 patients. Patients who do not receive the minimum cell dose or who do not receive the T‑cell infusion may be replaced
Patients must be: ≥ 18 years old; HLA-A*02:01, *02:05, or *02:06 positive; have advanced (metastatic or inoperable) MRCLS expressing NY-ESO-1 at 2+/3+ intensity in ≥30% of tumor cells by immunohistochemistry (IHC); measurable disease; prior systemic anthracycline therapy; have ECOG status 0 or 1; and adequate organ function
Lymphodepletion regimen: fludarabine (30mg/m2/day) and cyclophosphamide (600 mg/m2/day) for 3 days; same as Cohort 4 in Synovial Sarcoma study
Target dose of 1 – 8 × 109 transduced SPEAR T-cells
Efficacy assessed by overall response rate, time to response, duration of response, progression-free survival, and overall survival at weeks 4, 8, and 12, month 6, and then every 3 months until confirmation of disease progression
This study is open and actively enrolling
More about Soft Tissue Sarcomas
MRCLS and synovial sarcoma are both considered soft tissue sarcomas. MRCLS is a type of liposarcoma, characterized by the proliferation of adipocyte (fat cell) precursors called lipoblasts that have stopped differentiating. This malignancy arises from a translocation between chromosomes 12 and 16 resulting in a fusion protein that blocks adipocyte differentiation and promotes malignant transformation. Synovial sarcoma is characterized by a different chromosomal translocation involving the X chromosome and chromosome 18 and, unlike the known immature fat cell cellular origin of MRCLS, the cell of origin for synovial sarcoma remains unknown.

It is estimated that there are approximately 2000 patients in the United States and Europe with MRCLS each year. MRCLS has a peak incidence of occurrence in patients who are 30 to 50 years of age and it typically follows a more aggressive course than other liposarcomas. MRCLS also exhibits a unique presentation pattern arising first in the proximal areas of the extremities and typically spreading to the bones (particularly the spine), serosal surfaces, retroperitoneum, abdomen, pelvis, as well as to other soft tissues. This metastatic pattern is different from the characteristic pulmonary spread exhibited by synovial sarcoma.

Conference Call Information
The Company will host a live teleconference to answer questions about the updated safety data on June 4, 2018 at 8:00 a.m. EDT (1:00 p.m. BST). The live webcast of the conference call will be available via the events page of Adaptimmune’s corporate website at https://bit.ly/2shwniM. An archive will be available after the call at the same address. To participate in the live conference call, if preferred, please dial please dial +1-(833) 652-5917 (U.S.) or +1-(430) 775-1624 (International). After placing the call, please ask to be joined into the Adaptimmune conference call and provide the confirmation code (9199456).

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.