On June 5, 2018 VBL Therapeutics (NASDAQ:VBLT) reported data on its novel MOSPD2 program in oncology and inflammation at the 2018 BIO International Convention in Boston, Massachusetts (Press release, VBL Therapeutics, JUN 5, 2018, View Source [SID1234527188]).

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"Our research has shown that MOSPD2 plays a key role in the regulation of cell motility," said Dror Harats, M.D., Chief Executive Officer of VBL Therapeutics. "We have generated data indicating that MOSPD2 is required for directional movement, or chemotaxis, of tumor cells and certain immune cells, and therefore appears to play a central role in both oncology and inflammation. We continue to advance our exciting VB-600 series of antibodies as drug candidates for oncology and inflammatory indications."

MOSPD2 can be found in many types of solid tumors, and is highly expressed on tumor cells when they start invading tissues or creating metastatic lesions. VBL’s data indicate that knock-out of MOSPD2 in tumor cells may reduce metastasis by up to 95%. At the AACR (Free AACR Whitepaper) conference in April this year, VBL presented a late-breaking proof-of-concept study demonstrating antibody-mediated killing of MOSPD2-expressing cancer cells.

VBL research has also shown that knocking-out the MOSPD2 gene in mice could protect the animals from developing some inflammatory diseases. The Company has generated antibodies that block immune cell migration and show efficacy in a model of multiple sclerosis.

VBL is developing the VB-600 platform of biologic drug candidates for oncology and inflammatory indications. The Company plans to file an IND in this program by year-end 2019. For a webcast of VBL’s presentation at BIO see: LINK

On June 5, 2018 Polaris Group, a biopharmaceutical company focused on developing novel drugs for cancer, reported results from a phase 1 clinical study that features Polaris lead therapeutic candidate ADI‑PEG 20 in combination with pemetrexed and cisplatin (ADIPEMCIS) in first-line treatment for argininosuccinate synthetase (ASS1) deficient metastatic uveal melanomas (Press release, Polaris Pharmaceuticals, JUN 5, 2018, View Source [SID1234527207]). The results were presented by Dr. Peter Szlosarek from Barts Cancer Center in the UK (abstract No.2589) at the American Society Clinical Oncology’s 2018 annual meeting.

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ADIPEMCIS was well tolerated in a cohort of 10 patients. The best response was stable disease; which was observed in 7 of 10 patients and hence a disease control rate of 70%. The 12-month survival rate was 50% and the median overall survival is 11.5 months, with 1 patient still alive at 27.1 months.

Metastatic uveal melanoma has been resistant to systemic therapies, with low response rates and low overall survival. There is clearly an unmet medical need that requires the development of an effective and safe treatment for these patients. It has been observed previously that ADI‑PEG 20 had efficacy as a monotherapy in several earlier melanoma studies and now the combination with PEM/CIS has further enhanced the activity.

"ADIPEMCIS showed activity in these metastatic uveal melanoma patients," said John Bomalaski, M.D., Executive Vice President, Medical Affairs, of Polaris. "We believe that ADI‑PEG 20 would benefit these patients, for whom there is no established treatment regimen. Based on this encouraging data as well as for ADI‑PEG 20 monotherapy in uveal melanoma, a trial of ADI‑PEG 20 in combination with checkpoint inhibitors, including programmed death and CTLA-4 antibodies is planned for uveal melanoma patients."

About ADI-PEG 20

ADI‑PEG 20 is a biologic being developed by Polaris Group to treat cancers carrying a major metabolic defect that renders them unable to internally synthesize arginine. Because arginine is essential for protein synthesis and survival of cells, these cancer cells become dependent upon the external supply of arginine to survive and grow. ADI‑PEG 20 is designed to deplete the external supply of arginine, causing arginine-dependent cancer cells to die while leaving the patient’s normal cells unharmed. Multiple cancers have been reported to have a high degree of arginine-dependency and can potentially be treated with ADI‑PEG 20.

On June 4, 2018 Bristol-Myers Squibb Company (NYSE:BMY) reported updated results from the Phase 3 CheckMate -238 trial evaluating Opdivo (nivolumab) versus Yervoy (ipilimumab) in patients with stage IIIB/C or stage IV melanoma who are at high risk of recurrence following complete surgical resection (Press release, Bristol-Myers Squibb, JUN 4, 2018, View Source [SID1234527123]). In updated results from the study, Opdivo continued to demonstrate statistically longer recurrence-free survival (RFS) of 62.6%, the primary endpoint of the study, versus 50.2% for Yervoy (HR: 0.66, P<0.0001) at a minimum follow-up of 24 months across key subgroups, including disease stages and BRAF mutation status.

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No new safety data were generated as part of the 24-month analysis. As previously reported from the 18-month analysis, Opdivo demonstrated a significantly lower rate of adverse events (AEs) leading to discontinuation (9.7% of patients in the Opdivo arm compared to 42.6% of patients in the Yervoy arm) and treatment-related grade 3/4 AEs (14.4% of patients in the Opdivo arm compared to 45.9% in the Yervoy arm).

Findings will be presented on Monday, June 4 from 8:24-8:36 AM CDT during the Melanoma/Skin Cancers session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2018 in Chicago (Abstract #9502).

"The broader use of Immuno-Oncology agents has changed the cancer treatment landscape and, with advances in research, we have been able to extend the use of these agents to adjuvant therapy in melanoma in order to help prevent disease recurrence," noted Jeffrey S. Weber, M.D., Ph.D., principal investigator of CheckMate -238. "Results from the study’s 24-month follow-up, the longest follow-up of any PD-1 inhibitor in the adjuvant setting, continue to strongly support the benefit of nivolumab across multiple stages of melanoma and BRAF mutation status."

Arvin Yang, M.D., Ph.D., development lead, melanoma and genitourinary cancers, Bristol-Myers Squibb, said, "The updated CheckMate -238 data continue to show that adjuvant treatment can change the course of melanoma by preventing relapse and progression to an advanced stage."

Additional Data from CheckMate -238 at ASCO (Free ASCO Whitepaper) 2018

In the study, Opdivo demonstrated superior RFS versus Yervoy, regardless of disease stage, PD-L1 expression or BRAF mutation status, with RFS rates of 62.6% with Opdivo compared to 50.2% with Yervoy in the intent-to-treat patient population. In patients with stage IIIB melanoma, RFS rates at 24 months for Opdivo were 70.8% versus 60.7% with Yervoy; for patients with stage IIIC melanoma, RFS rates were 58.0% with Opdivo versus 45.4% with Yervoy; and for patients with stage IV melanoma, RFS rates for Opdivo were 58.0% versus 44.3% with Yervoy. In patients with BRAF mutant melanoma, RFS rates for Opdivo were 61.9% versus 51.7% with Yervoy; in patients with BRAF wild-type melanoma, Opdivo demonstrated a RFS of 63.5% versus 46.2% with Yervoy.

About CheckMate -238

CheckMate -238 is an ongoing Phase 3, randomized double-blind study of Opdivo versus Yervoy in patients who have undergone complete resection of stage IIIB/C or stage IV melanoma. The trial randomized 906 patients 1:1 to receive either Opdivo 3 mg/kg every two weeks (n=453) or Yervoy 10 mg/kg (n=453) every three weeks for four doses and then every 12 weeks starting at week 24. Patients were treated until disease recurrence, unacceptable toxicity or withdrawal of consent for up to one year. The primary endpoint is RFS, defined as the time between randomization and the date of first recurrence, new primary melanoma or death. After meeting the primary endpoint, the trial will continue to evaluate for overall survival, a secondary endpoint.

Adjuvant Therapy in Melanoma

Melanoma is separated into five staging categories (stages 0 to 4) based on the in-situ feature, thickness and ulceration of the tumor, whether the cancer has spread to the lymph nodes, and how far the cancer has spread beyond lymph nodes.

Stage III melanoma has reached the regional lymph nodes but has not yet spread to distant lymph nodes or to other parts of the body (metastasized), and requires surgical resection of the primary tumor as well as the involved lymph nodes. Some patients may also be treated with adjuvant therapy. Despite surgical intervention and possible adjuvant treatment, most patients experience disease recurrence and progress to metastatic disease. By five years, the majority of stage IIIB and IIIC patients (68% and 89%, respectively) experience disease recurrence.

On June 4, 2018, a poster titled "Pharmacodynamics and Genomic Profiling of Patients Treated With Cabiralizumab + Nivolumab Provide Evidence of On-Target Tumor Immune Modulations and Support Future Clinical Applications" was presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Presentation, Five Prime Therapeutics, JUN 4, 2018, View Source [SID1234527139]).

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On June 4, 2018 SELLAS Life Sciences Group, Inc. (NASDAQ:SLS) ("SELLAS" or "the Company") reported that interim Phase 1 data of GPS in combination with nivolumab in patients with WT1+ ovarian cancer in second or third remission after salvage chemotherapy at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Sellas Life Sciences, JUN 4, 2018, View Source [SID1234527155]). The presentation, "A phase I study of concomitant galinpepimut-S (GPS) in combination with nivolumab (nivo) in patients (pts) with WT1+ ovarian cancer (OC) in second or third remission," is being delivered by Roisin E. O’Cearbhaill, M.D., Gynecologic Medical Oncology Service, Memorial Sloan Kettering Cancer Center, during the "Gynecologic Cancer" session from 1:15 to 4:45 p.m. CT. The primary endpoint of the study is safety and assessment of toxicity, and treatment is continued until disease progression or toxicity. The secondary endpoint is immune response, and the exploratory endpoints include landmark 1-year PFS rate compared to historical controls and correlative analyses between clinical and immune responses.

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Exploratory efficacy interim data from this open-label Phase 1 investigator-sponsored trial showed that GPS, when combined with a PD-1 inhibitor, demonstrated PFS of 64% at one year in an intent to treat (ITT) group of 11 evaluable patients with WT1+ ovarian cancer in second or greater remission. Among patients who received at least three doses of GPS in combination with nivolumab, PFS at one year was 70% (7/10). The historical rates with best standard treatment do not exceed 50% in this disease setting. The most common adverse events were Grade 1 or 2, including fatigue and injection site reactions. Dose limiting toxicity was observed in one patient, following the second dose of the combination. No additional adverse event burden was observed for the combination as compared to nivolumab monotherapy. WT1 is a tumor antigen that is expressed in about half of ovarian cancers. The combination induced a high frequency of T- and B-cell immune responses.

Based on these safety, clinical activity and immunogenicity data, SELLAS expects to initiate a Phase 1/2 clinical study of GPS in combination with the PD-1 inhibitor pembrolizumab in a variety of tumor types, including WT1+ ovarian cancer in the third quarter of 2018.

"Patients with advanced relapsed ovarian cancer, in which WT1 is highly expressed, have few treatment options with limited efficacy," said Angelos Stergiou, MD, ScD h.c., President & Chief Executive Officer of SELLAS. "The interim data being presented today further support the therapeutic potential of GPS in high-risk cancer populations, including ovarian cancer. In this Phase 1 trial, the combination of GPS and nivolumab showed promising clinical and immune response activity with no additional adverse event burden as compared to nivolumab monotherapy, warranting further evaluation. These data bolster our commitment to developing GPS, alone and in combination, across a wide range of cancers, and we look forward to initiating our Phase 1/2 basket trial investigating the combination of GPS with pembrolizumab in five WT1+ tumor types, including ovarian, small cell lung, colorectal and triple negative breast cancer and acute myeloid leukemia."

Of the 11 patients evaluated:

7 patients were in second remission and 4 patients were in third remission
10 patients received six total doses of GPS (800 mcg) over 12 weeks in combination with seven infusions of I.V. nivolumab (3 mg/kg) over 14 weeks
all underwent toxicity assessments with each dose of GPS, and three weeks after the completion of therapy at Week 15. Non-progressors at Week 15 were permitted to receive four additional GPS doses, administered every eight weeks.
With regard to clinical and immune responses:

in 11 evaluable patients, the landmark 1-year PFS rate was 64% in the ITT group and 70% in the ten patients who received at least three doses of GPS + nivolumab. Historical rates do not exceed 50% in this disease setting
serum levels of antigen-specific IgG, against both individual WT1 peptides within GPS and the full-length WT1 protein, were induced in 86% of patients
achievement of high titers of WT1-specific IgG post-GPS results from Immunoglobulin (Ig) M to IgG class switching, the latter being a surrogate marker of induction of activated T-helper (Th) cells after vaccination
antigen-specific T-cell responses to individual WT1 peptides were observed between Weeks 6-15, primarily CD4 T-cells and, to a smaller extent, CD8 T-cells
"Effective consolidation or maintenance strategies are needed to prevent further recurrence or to prolong remission in patients with ovarian cancer after successful salvage from a previous relapse. In this setting, immune-directed therapy with a combination of blocker nivolumab and GPS, a multivalent, heteroclitic peptide vaccine targeting WT1, an antigen expressed in about half of ovarian cancers, led to high rates of antigen-specific immunization. We anticipate that this enhanced immunogenicity will translate into a reduction in relapses in larger studies," mentioned Dr. O’Cearbhaill. She added "these encouraging interim data suggest that the combination of GPS plus PD-1 inhibitors deserves further study in WT1+ ovarian cancer."

About Galinpepimut-S (GPS):
GPS is a heteroclitic multivalent, multi-peptide cancer immunotherapeutic agent composed of four peptides, addressing over 20 epitopes, and derived from the WT1 protein, which has been ranked by the National Cancer Institute as a top priority among cancer antigens for immunotherapy. Importantly, because the WT1 antigen is overexpressed in many malignancies, and is not found in most normal tissues, GPS has the potential to be a broad immunotherapy, effective across a multitude of diverse cancer types and patient populations.