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Atossa Genetics Enrolls First Cohort of Eight Subjects in Endoxifen Study

On April 4, 2017 Atossa Genetics, Inc. (NASDAQ: ATOS) reported that it has fully enrolled the first of six cohorts (eight participants per cohort) in its Phase 1 study of endoxifen, which is an active metabolite of tamoxifen, an FDA approved drug for breast cancer and breast cancer prevention in high risk women (Press release, Atossa Genetics, APR 4, 2017, View Source [SID1234518472]). The objectives of this double-blinded, placebo-controlled, repeat dose study of 48 healthy female subjects is to assess the pharmacokinetics of proprietary formulations of both oral and topical endoxifen dosage forms over 28 days, as well as to assess safety and tolerability. The study is being conducted in two parts based on route of administration.

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"Less than ten months ago we announced that we had begun a program to develop endoxifen for cancer patients who don’t benefit from taking tamoxifen and for women at high risk of developing breast cancer who are not taking tamoxifen, often due to concerns about side effects from system exposure. Through the hard work and dedication of Atossa’s employees and our collaborators we have obtained a qualified manufacturer of the active pharmaceutical ingredient, performed formulation development for both oral and topical dosage forms, established a manufacturer of the finished dosage forms, and launched the first human testing in a Phase 1 study," stated Steven Quay, CEO and President. "I am not aware of any oncology company that has completed the pre-clinical phase of drug development so quickly."

Galena Biopharma Presents Positive Interim Safety Data on the NeuVax™ (nelipepimut-S) Clinical Trial in Combination with Trastuzumab in High-Risk HER2 3+ Patients at the AACR Annual Meeting 2017

On April 4, 2017 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company developing hematology and oncology therapeutics that address unmet medical needs, reported a poster was presented on the Company’s NeuVax (nelipepimut-S) investigator-sponsored Phase 2 clinical trial (IST) in high-risk, HER2 3+ patients at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 in Washington, DC (Press release, Galena Biopharma, APR 4, 2017, View Source [SID1234518471]). The Phase 2 trial is a multi-center, prospective, randomized, single-blinded, placebo-controlled trial combining NeuVax and trastuzumab in the adjuvant setting to prevent recurrence in HER2-positive (HER2 3+) breast cancer patients.

The poster, entitled, "Pre-specified interim analysis in a prospective, randomized phase II trial of trastuzumab vs trastuzumab + NeuVax to prevent breast cancer recurrence in HER2+ breast cancer patients," presented the interim safety analysis that was initiated after enrollment of the 50th patient in the trial (vaccine group (VG) n=22, control group (CG) n=28). The analysis demonstrated that the agent is well tolerated with no increased cardiotoxicity associated with giving NeuVax in combination with trastuzumab.

In the trial, there were no significant clinicopathologic differences between groups. The vast majority of toxicities were grade 1 and there were no related grade 4 or 5 toxicities and no differences in related toxicities between the VG and CG (Grade 1: 96% vs 98.5%; Grade 2: 3.2% vs 1.5%; Grade 3: 0.8% vs 0%, p=0.14). There was no significant reduction in cardiac ejection fraction (EF) pre- to post-treatment in either group (VG: 61.1±5.4% vs 60.1±4.8%, p=0.55; CG: 62.3±5.7% vs 61.9±4.0%, p=0.74) and no notable difference in EF was observed between the baseline (pre-treatment) and the follow-up (post treatment) within the vaccine and control groups (p=0.54).

"As we reported in February, this data was the basis for the Data Safety Monitoring Board (DSMB) to perform a futility analysis and recommend the study continue as planned. Additionally, the DSMB determined that there were no safety concerns," said Bijan Nejadnik, M.D., Executive Vice President and Chief Medical Officer. "The poster presented at AACR (Free AACR Whitepaper) provides a more detailed safety analysis of the ongoing IST with NeuVax in combination with trastuzumab in HER2 positive breast cancer patients. We are pleased that the combination of agents are well tolerated and that there is no additive cardio toxicity."

Dr. Nejadnik continued, "The Phase 2 trial is expected to complete enrollment by the end of this year with immunologic and clinical outcomes data to be reported via the planned primary analysis after 24-months follow-up. This trial in HER2 3+ patients complements our other ongoing IST with NeuVax in combination with trastuzumab in HER2 1+/2+ patients with an interim data analysis also expected by the end of the year."

The trial is enrolling HLA-A2 and HLA-A3 positive breast cancer patients with stage I-III HER2 positive disease at high risk for recurrence, which is defined as patients not achieving a complete response after trastuzumab-containing neoadjuvant therapy or those undergoing up-front surgery with any node-positive disease (if ER/PR- or ≥4 positive nodes if ER/PR+). Patients are enrolled after surgery, radiation and neo-adjuvant/adjuvant chemotherapy with an approved trastuzumab-containing regimen. Patients are randomized to receive trastuzumab + NeuVax in the VG or trastuzumab + GM-CSF only in the CG. Patients receive vaccinations of NeuVax or GM-CSF intradermally every 3 weeks for 6 total vaccinations (primary vaccine series, PVS) starting with the third dose of trastuzumab maintenance therapy. Starting 6 months after the completion of the PVS, patients receive 4 booster inoculations, one every 6 months. EF is assessed by either echo or MUGA at baseline and serially during treatment. For this analysis, demographic and safety data were collected and analyzed, and the interim safety analysis was initiated after enrollment of the 50th patient.

The abstract (#8734) can be found on the conference website here, and the poster presentation from the conference will be available on Galena’s website here.

About NeuVax (nelipepimut-S)

NeuVax (nelipepimut-S) is a first-in-class, HER2-directed cancer immunotherapy under evaluation to prevent breast cancer recurrence after standard of care treatment in the adjuvant setting. It is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut-S sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTLs) following binding to specific HLA molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy, through cell lysis, HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut-S immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. In clinical studies, NeuVax is combined with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF).

NeuVax is currently in two breast cancer studies in combination with trastuzumab (Herceptin; Genentech/Roche): a Phase 2b trial in node positive and triple negative HER2 IHC 1+/2+ (clinicaltrials.gov identifier: NCT01570036); and, a Phase 2 trial in high risk, node positive or negative HER2 IHC 3+ patients (clinicaltrials.gov identifier: NCT02297698). A Phase 2 clinical trial is also ongoing with NeuVax in patients with ductal carcinoma in situ (DCIS) (clinicaltrials.gov identifier: NCT02636582), and a Phase 2 trial is planned in patients with gastric cancer.

About Breast Cancer1

New cases of breast cancer occur at an annual rate of 125 per 100,000 women in the U.S., with an estimated 246,660 new cases and 40,450 deaths in 2016. Approximately 89.7% of breast cancer patients are expected to survive five years after diagnosis. Approximately 12.4% of women will be diagnosed with breast cancer at some point during their lifetime (2011 – 2013 data). The prevalence data from 2013 showed an estimated 3,053,450 women living with breast cancer in the United States.

VBL Therapeutics Presents Data on MOSPD2, a Novel Immuno-Oncology Target

On April 4, 2017 VBL Therapeutics (NASDAQ:VBLT), reported the presentation of new data on MOSPD2, a novel potential target in oncology (Press release, VBL Therapeutics, APR 4, 2017, View Source [SID1234518470]). VBL’s study, entitled "MOSPD2, a Newly Characterized Protein, Promotes Breast Cancer Metastasis" by Mendel et al., will be presented today at the American Association of Cancer research (AACR) (Free AACR Whitepaper) conference in Washington, DC. The study observed from clinical biopsies that MOSPD2 is prevalent in invasive human breast cancer tissue and that levels of MOSPD2 correlate to breast cancer invasiveness. It was further observed that a knockdown of MOSPD2 in a human breast cancer cell line using CRISPR technology led to blockade of EGF signaling and significant reduction of breast cancer cell migration in vitro and metastasis in a mouse model.

"The current publication indicates involvement of MOSPD2 in motility and metastasis of cancer cells in a breast cancer model, with correlative clinical specimens expression pattern that is associated with breast tumor invasiveness," said Eyal Breitbart, PhD, VP for Research and Operations at VBL. "We believe that MOSPD2 may be involved in the regulation of cell motility in addition to breast cancer, as it is found in other tumor tissues as well. We recently reported its role in monocyte migration and are studying its expression and potential involvement in additional tumor types," added Dr. Breitbart.

The company believes that targeting of MOSPD2 may have several therapeutic applications, including inhibition of tumor cell metastases and targeting of MOSPD2-positive tumor cells, as well as inhibition of monocyte migration in chronic inflammatory conditions. VBL’s "VB-600 series" of pipeline candidates is being developed towards these applications.

TG Therapeutics, Inc. Announces Preclinical Data Presentation on the Company’s Anti-PD-L1 Monoclonal Antibody at the American Association for Cancer Research Annual Meeting

On April 4, 2017 TG Therapeutics, Inc. (NASDAQ:TGTX), reported the first presentation of preclinical data on the Company’s novel fully human anti-PD-L1 monoclonal antibody at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, being held this week, April 1-5, 2017, at the Walter E. Washington Convention Center in Washington, D.C (Press release, TG Therapeutics, APR 4, 2017, View Source [SID1234518469]).

The following poster was presented today, April 4, 2017, during the Immunoconjugates and Antibodies Session in Halls A-C.

Preclinical Characterization of a Novel Fully Human lgG1 Anti-PD-L1 mAb CK-301

Based on the various assays performed, the poster concluded:

CK-301 is a high affinity PD-L1 specific fully humanized lgG1 antibody which blocks binding of PD-L1 to PD-1.
Activity of CK-301 in all assays tested was similar to anti-PD-L1’s used as active controls (surrogates of avelumab, atezolizumab, or durvalumab).
Similar to the approved anti-PD-L1, avelumab, CK-301 has the potential to induce ADCC (antibody-dependent cell-mediated cytotoxicity).
A first-in-human Phase 1 study of CK-301 is planned to commence this year.

Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer stated, "The team has worked hard to develop a high quality anti-PD-L1 antibody which we believe is the cornerstone of any proprietary immune-oncology (I/O) strategy. While anti-PD-1/PD-L1 therapy has been broadly explored in solid tumors, we are still in the very early days of understanding their utility and best applications in B-cell malignancies. As a company, we have been highly focused on developing best-in-class combination therapies for patients with B-cell malignancies and believe the next generation of combinations will include both targeted therapies, like TG-1101 and TGR-1202, plus I/O agents like our anti-PD-L1 antibody presented here today. We look forward to commencing the first-in-human study this year."

Karyopharm Reports Interim Phase 2b SADAL Data at the 2017 American Association for Cancer Research Annual Meeting

On April 4, 2017 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported that updated interim clinical data from its Phase 2b Selinexor Against Diffuse Aggressive Lymphoma (SADAL) study evaluating lead product candidate, selinexor (KPT-330), an oral Selective Inhibitor of Nuclear Export / SINE compound, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) was presented today in a late-breaking poster at the 2017 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in Washington, DC (Press release, Karyopharm, APR 4, 2017, View Source [SID1234518468]). In the SADAL study, selinexor achieved a 28.6% overall response rate (ORR) in patients with relapsed or refractory DLBCL. Importantly, the responses were shown to be durable with a median duration of response (DOR) of greater than seven months, including prolonged complete responses (CRs).

"Data from the ongoing SADAL study demonstrate robust single-agent activity of selinexor and prolonged response rates in this heavily pretreated DLBCL patient population, including against both the GCB and non-GCB (ABC) subtypes," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "The observed response rates were consistent across both the 60mg and 100mg treatment arms, but greater durability and tolerability was observed in the 60mg arm. Based on these results and following agreement with FDA, a study amendment is underway to discontinue the 100mg treatment arm and focus solely on the 60mg treatment arm where we plan to add approximately 90 patients. We look forward to reporting top-line data from the SADAL study in mid-2018. Should the data confirm the current results, we plan to apply for accelerated approval for the treatment of relapsed / refractory DLBCL."
Updated Phase 2b SADAL Clinical Data in Relapsed or Refractory DLBCL

In a late-breaking poster presentation titled, "A Phase 2b randomized study of selinexor in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) demonstrates durable responses in both GCB and non-GCB subtypes," Marie Maerevoet, MD of the Institute Jules Bordet in Belgium presented updated clinical data from the ongoing Phase 2b SADAL study.

A summary of the efficacy data as presented at AACR (Free AACR Whitepaper) 2017 is outlined in the following table and described below.

Targeting Disease at the Nuclear Pore

Best Responses* in Patients as of 1 March 2017

Category
N ORR (%) DCR (%) CR (%) PR (%) SD (%) PD (%) NE (%)
All patients
63 18 (28.6 %) 27 (42.9 %) 7 (11.1 %) 11 (17.5 %) 9 (14.3 %) 29 (46.0 %) 7 (11.1 %)
60 mg
32 9 (28.1 %) 12 (37.5 %) 4 (12.5 %) 5 (15.6 %) 3 (9.4 %) 17 (53.1 %) 3 (9.4 %)
100 mg
31 9 (29.0 %) 15 (48.4 %) 3 (9.7 %) 6 (19.4 %) 6 (19.4 %) 12 (38.7 %) 4 (12.9 %)
GCB-Subtype
32 8 (25.0 %) 14 (43.8 %) 3 (9.4 %) 5 (15.6 %) 6 (18.8 %) 13 (40.6 %) 5 (15.6 %)
Non-GCB-Subtype
31 10 (32.3 %) 13 (41.9 %) 4 (12.9 %) 6 (19.4 %) 3 (9.7 %) 16 (51.6 %) 2 (6.5 %)

* Responses were adjudicated according to the Lugano Classification (Cheson, 2014) by an independent central radiological review committee. ORR=Overall Response Rate (CR+PR), CR=Complete Response, PR=Partial Response, SD=Stable Disease, PD=Progressive Disease, DCR=Disease Control Rate (CR+PR+SD), NE=Not Evaluable for Response. Responses as of March 1, 2017 based on interim unaudited data.

Based on the intention-to-treat analysis of the first 63 patients (median of 3 prior treatment regimens (range 2-5)), as adjudicated by an independent central radiological committee, 18 patients responded (7 patients with a CR and 11 patients with a PR) for an ORR 28.6%. An additional 9 patients experienced SD, for a DCR of 42.9%. The median overall survival was 8 months for all patients, consistent with published data in this population. As of the data cutoff date, median survival for the responders had not been reached and is over 9 months. The median DOR across all patients was greater than 7 months and responses tended to occur rapidly with a median of 2 months to onset. Among patients who responded, the median time on treatment was 9 months with a follow up of 13 months. As of the data cutoff date, 9 patients who responded remained on treatment, including 6 patients with a CR.

Selinexor showed similar activity against GCB and non-GCB subtypes of DLBCL: Of the 32 patients with DLBCL of the GCB-subtype, 8 responded (3 patients with a CR, 5 patients with a PR and 6 patients with SD) for an ORR of 25.0% and DCR of 43.8%. Of the 31 patients with DLBCL of the non-GCB-subtype (ABC), 10 responded (4 patients with a CR, 6 patients with a PR and 3 patients with SD) for an ORR of 32.3% and DCR of 41.9%.

Among the 72 patients evaluated for safety, the most common adverse events (AEs) across both dosing groups were fatigue (65%), thrombocytopenia (54%), nausea (51%), anorexia (49%), vomiting (35%) and anemia (32%), and were primarily grades 1 and 2 and were managed with dose modifications and/or standard supportive care. As expected, the most common grade 3 and 4 AEs in the 60mg arm were thrombocytopenia (32%), neutropenia (16%), anemia (14%), and fatigue (11%) and were manageable with dose modifications and/or standard supportive care.

Dr. Maerevoet commented, "With the impressive and durable responses observed to date, including in both the GCB and non-GCB subtypes of DLBCL, single-agent selinexor is demonstrating the potential to become a new oral option for this difficult to treat patient population who are not candidates for transplantation and whose disease is unlikely to respond to further chemotherapy or targeted agents."

Planned Development Path for Selinexor in DLBCL

As a result of the interim data and in consultation with FDA, Karyopharm is amending the SADAL study protocol to become a single-arm study focusing solely on single-agent selinexor dosed at 60mg twice weekly, eliminating the 100mg arm. The study is also being amended to reduce the 14-week treatment-free period to 8 weeks in patients who achieved at least a PR on their most recent therapy. Patients who were refractory or did not achieve at least a PR on their prior therapy will continue with the 14-week treatment-free period. The FDA agreed that the modification to a single-arm study was reasonable and that the proposed trial design and indication appear appropriate for accelerated approval, though eligibility for accelerated approval will depend on the complete trial results and available therapies at the time of regulatory action. The Company plans to enroll up to an additional 90 patients to the new 60mg single-arm cohort and expects to report top-line results from the SADAL study in mid-2018.

Title: A Phase 2b randomized study of selinexor in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) demonstrates durable responses in both GCB and non-GCB subtypes
Presenter: Marie Maerevoet, Institute Jules Bordet
Poster Board #: 13
Session: Phase I-III Clinical Trials and Pediatric Clinical Trials
Location: Convention Center, Halls A-C, Poster Section 33
Date and Time: Tuesday, April 4, 2017 from 1:00 PM – 5:00 PM ET
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Targeting Disease at the Nuclear Pore

About Selinexor
Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 1,900 patients have been treated with selinexor and it is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Karyopharm plans to initiate a pivotal randomized Phase 3 study of selinexor in combination with bortezomib (Velcade) and low-dose dexamethasone (BOSTON) in patients with multiple myeloma in early 2017. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the Company’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.