On April 27, 2020 Verastem, Inc. (Nasdaq:VSTM) (also known as Verastem Oncology), a biopharmaceutical company committed to developing and commercializing new medicines for patients battling cancer, reported results from the ongoing investigator-initiated Phase 1 clinical study investigating VS-6766, its RAF/MEK inhibitor, in combination with defactinib, its FAK inhibitor, in patients with KRAS mutant advanced solid tumors (Press release, Verastem, APR 27, 2020, View Source [SID1234556603]). The data will be presented as a virtual poster today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting I.

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This ongoing study is an open label, dose escalation and expansion study. The expansion cohorts are currently ongoing in patients with advanced solid tumors, including low-grade serous ovarian cancer (LGSOC), KRAS mutant non-small cell lung cancer (NSCLC) and KRAS mutant colorectal cancer (CRC). In the LGSOC cohort, among the patients with KRAS mutant tumors (n=6), 4 patients responded, for an overall response rate (ORR) of 67%. Median time on treatment was 20.5 months. In the KRAS mutant NSCLC cohort (n=10), 1 patient achieved a partial response and 8 patients achieved disease control. In this cohort, 70% of patients continued on treatment at least 12 weeks and 30% of patients continued on treatment at least 24 weeks.

Based on an observation of higher response rates seen in patients with KRASG12V mutations in the investigator-initiated Phase 1 combination study, we conducted a combined analysis with data from the combination study and the prior single-agent study that utilized a twice-weekly dosing schedule of VS-67661 to get a more complete picture of activity in KRASG12V mutations. The subsequent, combined analysis (VS-6766 monotherapy and defactinib combination) showed a 57% ORR (4/7 patients); as a single agent (2/5 patients) and in combination with defactinib (2/2 patients) in KRASG12V mutant NSCLC. Similarly, the combined analysis showed a 60% ORR (3/5 patients); as a single agent (1/2 patients) and in combination with defactinib (2/3 patients) in KRASG12V mutant gynecologic cancers. These additional analyses were conducted by Verastem Oncology to understand the impact that various KRAS variants may have had on response to identify potential signals to pursue in future prospective studies. This additional analysis was not part of the AACR (Free AACR Whitepaper) 2020 poster presentation.

"Earlier research has demonstrated MEK inhibitors can cause upregulation of FAK in KRAS mutant tumors, which are notoriously difficult to treat and quite common across solid tumors. The combination of a RAF/MEK and FAK inhibitor can potentially overcome this challenge and opens up an exciting new pathway for treatment," stated Professor Udai Banerji, Professor of Molecular Cancer Pharmacology at The Institute of Cancer Research, London, and Honorary Consultant in Medical Oncology, MBBS, MD, DNB, PhD, FRCP at The Royal Marsden NHS Foundation Trust, London, and lead investigator of the clinical study. "We found that the combination of VS-6766 and defactinib in low-grade serous ovarian cancer (LGSOC) was well tolerated by the patients in the trial and shows promising clinical activity, including durable response that is associated with clinically meaningful benefit. The study continues to enroll additional patients into the ovarian, lung and colorectal expansion cohorts with additional responses seen in all cohorts."

"We are encouraged by these early response rates in KRAS mutant LGSOC and in KRASG12V mutant tumors as they underscore the significant potential of this novel approach in areas of high unmet medical need," said Brian Stuglik, Chief Executive Officer of Verastem Oncology. "The potential of the combination of VS-6766 and defactinib is rapidly evolving as we continue to gain more insights and analyze the data. We plan to initiate discussions with regulatory authorities as soon as possible to define a path forward, with the goal of commencing a registration-directed clinical trial during 2020."

Initial Results from the Phase 1 Study Investigating the Combination of VS-6766 and Defactinib in Patients with KRAS Mutant Cancers and Subsequent Analyses

The poster presentation describes safety and dose response data from the dose-escalation portion and expansion cohorts from an open-label, investigator-initiated Phase 1 study conducted in the United Kingdom assessing the combination of RAF/MEK and FAK inhibitor therapy in patients with LGSOC and KRAS mutant NSCLC. The study evaluated the combination of VS-6766 and defactinib. VS-6766 was administered using a twice-weekly dose escalation schedule and was administered 3 out of every 4 weeks. Defactinib was administered using a twice-daily dose escalation schedule, also 3 out of every 4 weeks. Dose levels were assessed in 3 cohorts: cohort 1 (VS-6766 3.2mg, defactinib 200mg); cohort 2a (VS-6766 4mg, defactinib 200mg); and cohort 2b (VS-6766 3.2mg, defactinib 400mg).

In the patients with LGSOC (n=8), the ORR was 50% (n=4). Among the patients with KRAS mutant LGSOC (n=6), the ORR was 67% (n=4). Of the 4 patients who have responded, 3 had a prior MEK inhibitor and as of November 2019 had been on study for a median of 20.5 months (range 7-23 months). In the patients with NSCLC (n=10), all of which had KRAS mutations, 1 patient achieved a partial response and 1 patient with a 22% tumor reduction still on treatment as of November 2019. Median time on treatment for this cohort was approximately 18 weeks.

Based on an observation of higher response rates seen in patients with KRASG12V mutations in the investigator-initiated Phase 1 combination study, we conducted a combined analysis with data from the combination study and the prior single-agent study that utilized a twice-weekly dosing schedule of VS-67661 to get a more complete picture of activity in KRASG12V mutations. The subsequent, combined analysis (VS-6766 monotherapy and defactinib combination) showed a 57% ORR (4/7 patients); as a single agent (2/5 patients) and in combination with defactinib (2/2 patients) in KRASG12V mutant NSCLC. Similarly, the combined analysis showed a 60% ORR (3/5 patients); as a single agent (1/2 patients) and in combination with defactinib (2/3 patients) in KRASG12V mutant gynecologic cancers. These additional analyses were conducted by Verastem Oncology to understand the impact that various KRAS variants may have had on response to identify potential signals to pursue in future prospective studies. This additional analysis was not part of the AACR (Free AACR Whitepaper) 2020 poster presentation.

The most common side effects seen in the Phase 1 study were rash, creatine kinase elevation, nausea, hyperbilirubinemia and diarrhea, most being NCI CTC Grade 1/2 and all were reversible. The recommended Phase 2 dose was determined to be cohort 1 (VS-6766 3.2mg, defactinib 200mg).

The preliminary data reported in the study suggest that a novel intermittent dosing schedule of RAF/MEK and FAK inhibitor combination therapy has promising clinical activity in patients with KRASmutant LGSOC and KRASG12V mutant NSCLC, including patients previously treated with a MEK inhibitor. Expansion cohorts remain ongoing.

Details for the AACR (Free AACR Whitepaper) 2020 Virtual Meeting I presentation are as follows:

Title: Phase 1 study of the combination of a RAF-MEK inhibitor CH5126766 (VS-6766) and FAK inhibitor defactinib in an intermittent dosing schedule with expansions in KRAS mutant cancers
Lead author: Udai Banerji, The Institute of Cancer Research and The Royal Marsden
Poster #: CT143
Session: VPO.CT01 – Phase I Clinical Trials
Date and Time: Monday, April 27, 2020; 9:00 a.m. to 6:00 p.m. ET
URL: View Source!/9045/presentation/10642

Conference Call and Webcast Information

The Verastem Oncology management team will host a conference call and webcast on Monday, April 27, 2020, at 8:00 AM ET to discuss the Phase 1 RAF/MEK/FAK combination data. The call can be accessed by dialing (877) 341-5660 (U.S. and Canada) or (315) 625-3226 (international), five minutes prior to the start of the call and providing the passcode 8390795.

The live, listen-only webcast of the conference call can be accessed by visiting the investors section of the Company’s website at www.verastem.com. A replay of the webcast will be archived on the Company’s website for 90 days following the call.

About VS-6766

VS-6766 (formerly known as CH5126766, CKI27 and RO5126766) is a unique inhibitor of the RAF/MEK signaling pathway. In contrast to other MEK inhibitors in development, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The combination of VS-6766 and the focal adhesion kinase (FAK) inhibitor defactinib is currently being investigated in an investigator-initiated Phase 1 dose escalation and expansion study. The expansion cohorts are currently ongoing in patients with KRAS mutant advanced solid tumors, including low grade serous ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).2 The ongoing clinical study of the VS-6766/defactinib combination is supported by single-agent Phase 2 studies which investigated defactinib in KRAS mutant NSCLC3 and VS-6766 in KRAS mutant NSCLC and LGSOC.1

About Defactinib

Defactinib is an oral small molecule inhibitor of FAK and PYK2 that is currently being evaluated as a potential combination therapy for various solid tumors. The Company has received Orphan Drug designation for defactinib in ovarian cancer and mesothelioma in the US, EU and Australia. Preclinical research by Verastem Oncology scientists and collaborators at world-renowned research institutions has described the effect of FAK inhibition to enhance immune response by decreasing immuno-suppressive cells, increasing cytotoxic T cells, and reducing stromal density, which allows tumor-killing immune cells to enter the tumor.4,5 Additionally, in both preclinical and clinical studies, FAK activation has been shown to occur as a potential resistance mechanism in response to MEK inhibitor treatment, and synergy of a FAK inhibitor with a RAF/MEK inhibitor has been shown in several preclinical models. The combination of defactinib and VS-6766 is currently being investigated in an investigator-initiated Phase 1 dose escalation and expansion study. The expansion cohorts are currently ongoing in patients with KRAS mutant advanced solid tumors, including low grade serous ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).2 The ongoing clinical study of the VS-6766/defactinib combination is supported by single-agent Phase 2 studies which investigated defactinib in KRAS mutant NSCLC3 and VS-6766 in KRAS mutant NSCLC and LGSOC.4 Defactinib is also in clinical testing in combination with pembrolizumab for treatment of patients with pancreatic cancer, NSCLC and mesothelioma.6

On April 26, 2024 The research team of Professor Min Jeong-jun and Kang Se-ryeong of the Department of Nuclear Medicine at Hwasun Chonnam National University Hospital recently reported the company developed the world’s first ‘positron emission tomography (PET) molecular imaging technology’ that visualizes bacteria for cancer treatment (Press release, CNCure, APR 26, 2020, View Source [SID1234649029]).

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This technology is registered as a domestic patent, and overseas patents are also being applied for. This research was first introduced in the online version of ‘Theranostics’ (impact factor 8.063), an authoritative international academic journal in the field of molecular imaging diagnosis and treatment, and is scheduled to be published as a cover paper in the upcoming June issue.

The research team succeeded in visualizing E. coli injected into the body for cancer treatment using radioactive sorbitol. Based on the fact that ‘sorbitol’, a substance produced by reducing glucose, is used as a nutrient for gram-negative intestinal bacteria such as E. coli and salmonella, they attempted PET imaging by producing sorbitol containing radioactive fluorine.

This sorbitol PET accurately showed the distribution of E. coli injected for treatment purposes in the body. It was analyzed that the greater the amount of sorbitol consumed in the tumor, the greater the cancer suppression effect.

In cell therapy using living immune cells or microorganisms, the distribution of the therapeutic agent in the tumor is very important. In other words, the therapeutic cells must be concentrated in the tumor area and removed from other organs in the body for the treatment to be effective and safe. Therefore, a molecular imaging technique that can evaluate the distribution of the therapeutic agent in the body in a non-invasive way that does not penetrate the skin is a very important technology that determines the success or failure of this treatment. Until now, in order to visualize bacteria for cancer treatment, it was necessary to artificially express image reporter genes, but in this study, visualization was successfully achieved using the unique mechanism of therapeutic bacteria without additional genetic manipulation, and the possibility of future clinical application is very high. This study was conducted with the support of the Ministry of Science and ICT’s Future Promising Convergence Technology Pioneer Project and the Ministry of Education’s Science and Technology Individual Basic Research Support Project. Reporter Jang Jong-ho [email protected]

On April 26, 2020 The University of Texas MD Anderson Cancer Center’s Therapeutics Discovery division and Ipsen Biopharmaceuticals reported the preclinical discovery and early-stage clinical development of this novel drug (Press release, MD Anderson, APR 26, 2020, View Source [SID1234556628]). IPN60090, now under investigation in a Phase I trial, may hold benefit for certain patients with lung and ovarian cancers.

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MD Anderson’s GLS1 program was initiated and advanced by a team of scientists in the Institute for Applied Cancer Science (IACS) and Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION) platforms, both engines within Therapeutics Discovery. Development of the program continues in collaboration with Ipsen, which licensed the therapeutic in 2018.

Findings and information about the ongoing trial will be presented today at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I by Jeffrey Kovacs, Ph.D., institute group leader with TRACTION and co-leader of the GLS1 program.

"This effort is a great example of our strategy within Therapeutics Discovery, taking a comprehensive approach to personalized medicine," said Kovacs. "Our preclinical data suggest that IPN60090 may be effective in underserved groups of patients who need better treatment options, and we look forward to results from our ongoing clinical trials."

Dysregulation of cellular metabolism is a hallmark of cancer development, and the GLS1 enzyme plays a key role in many metabolic processes. Thus, it makes an attractive target for cancer therapy, explained Kovacs.

IACS drug-discovery scientists identified IPN60090 as a potent and selective inhibitor of GLS1 suitable for clinical trials, and translational researchers in TRACTION demonstrated its activity against subsets of lung and ovarian cancer preclinical models.

Further analysis revealed biomarkers of response, which have been leveraged to identify patients most likely to benefit. In lung cancers, mutations in the KEAP1 and NFE2L2 genes, which regulate response to oxidative stress, sensitize cells to treatment with IPN60090. Similarly, low expression of the metabolic protein asparagine synthetase (ASNS) in ovarian cancers predicts response to IPN60090 in preclinical models.

"Identifying these putative predictive biomarkers of response is critical for our ongoing clinical efforts to ensure that we’re able to offer patients the most relevant therapies," said Timothy A. Yap, M.B.B.S., Ph.D., F.R.C.P., associate professor of Investigational Cancer Therapeutics and medical director of IACS. "These patient groups in particular, which represent distinct niches within those cancer types, are in need of more effective treatment options."

For example, patients with lung cancers harboring KEAP1/NRF2 mutations have not benefited from treatment with immune checkpoint inhibitors and have poorer outcomes overall, explained Yap, who leads the IPN60090 clinical trial at MD Anderson.

IPN60090 currently is under investigation in a Phase I dose-escalation and dose-expansion study for patients with advanced solid tumors that harbor KEAP1/NFE2L2 mutations or have low ASNS levels. The team has developed novel CLIA-certified assays to identify patients likely to benefit and monitor how effectively the drug is acting. Initial data from the clinical trial indicate that IPN60090 is effectively inhibiting GLS1 activity in peripheral blood mononuclear cells from patients.

Future trial cohorts plan to investigate IPN60090 in combination with checkpoint inhibitors, chemotherapy and targeted therapies identified by the researchers as having potential synergistic benefits with GLS1 inhibition.

The ongoing research is supported by Ipsen through a global licensing and development agreement. The research is managed according to MD Anderson’s Institutional Conflict of Interest Management and Monitoring Plan. Kovacs is a co-inventor on material and method-of-use patent applications related to IPN60090. The Therapeutics Discovery division is supported in part by MD Anderson’s Moon Shots Program.

On April 26, 2020 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported the submission of a New Drug Application (NDA) to the Ministry of Health, Labour and Welfare (MHLW) by Janssen Pharmaceutical K.K. (Janssen) seeking approval of a new subcutaneous (SC) formulation of daratumumab, an intravenous (IV) treatment approved for patients with multiple myeloma (Press release, Halozyme, APR 26, 2020, View Source [SID1234556601]).

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"We are pleased to see this New Drug Application submission in Japan, which builds on Janssen’s prior regulatory submissions in the U.S. and EU that are currently under review," said Dr. Helen Torley, president and chief executive officer. "We are excited that patients with multiple myeloma in Japan may soon have a new therapeutic option that can be administered with a shorter infusion time when compared with a multi-hour intravenous infusion."

The NDA is supported by pivotal data from the Phase 3 COLUMBA (MMY3012) study – a randomized open label study – that included a non-inferiority comparison of daratumumab SC formulation versus daratumumab IV administration in patients with multiple myeloma who had received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease was refractory to both PI and IMiD. In addition to non-inferiority, daratumumab SC showed a lower rate of infusion-related reactions. Data from the Phase 2 PLEIADES (MMY2040) study – a non-randomized open label study conducted in newly diagnosed or relapsed or refractory multiple myeloma patients – are also included in the NDA. The subcutaneous formulation of daratumumab is co-formulated with Halozyme’s ENHANZE drug delivery technology, based on recombinant human hyaluronidase PH20 (rHuPH20).

About ENHANZE Technology
Halozyme’s proprietary ENHANZE drug delivery technology is based on its patented recombinant human hyaluronidase enzyme (rHuPH20). rHuPH20 has been shown to remove traditional limitations on the volume of biologics that can be delivered subcutaneously (just under the skin). By using rHuPH20, some biologics and compounds that are administered intravenously may instead be delivered subcutaneously. ENHANZE may also benefit subcutaneous biologics by reducing the need for multiple injections. This delivery has been shown in studies to reduce health care practitioner time required for administration and shorten time for drug administration.

On April 24, 2020 Oncocyte Corporation (NYSE American: OCX), a molecular diagnostics company with a mission to provide actionable answers at critical decision points across the cancer care continuum, reported that it has entered into definitive agreements with, among other institutional investors, Blackcrane Capital, LLC, an investment management company employing an unconstrained, change-oriented investment approach, to purchase approximately $10.7 million of Oncocyte’s common shares in a registered offering priced "at market", which was the closing price immediately preceding the offering (Press release, Oncocyte, APR 24, 2020, View Source [SID1234556663]). This offering was completed directly with the institutional investors and the Company incurred no placement agent fees.

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"Our continued ability to attract support from healthcare focused funds stems from our remarkable progress in advancing our expanding suite of tests which now address treatment stratification and immunotherapy response prediction for lung cancer and liquid biopsy to rule out malignancy in lung nodules," said Ron Andrews, Chief Executive Officer of Oncocyte. "Our strengthened balance sheet will facilitate our continued progress and execution, now as a commercial stage company, as we work to grow our market and further expand our offerings in lung and beyond."

Daniel Kim, founder and chief executive of Blackcrane Capital, LLC, said "We are excited to partner with Oncocyte as they work to provide decisive answers for patients across the lung cancer care continuum. We see tremendous potential at Oncocyte based on their deep clinical and commercial expertise and proven track record of success. We are very excited to support Oncocyte’s management team as it continues to work towards improving lung cancer diagnosis, treatment and patient outcomes."

In connection with the offering, the Company will sell an aggregate of 4,733,700 shares of its common stock at a purchase price of $2.27 per share, the closing price of the stock on April 23, 2020, the day prior to the execution of the agreement with the investors. The registered offering is subject to customary closing conditions and is expected to close during the week of April 27, 2020.

Proceeds from the registered offering provide the strategic capital to accelerate and support the commercial launch of DetermaRx, OncoCyte’s lung cancer treatment stratification test, DetermaIO, a research use only gene expression test to identify immune checkpoint inhibitor responders, and the continued development of DetermaDx a liquid biopsy test to rule out malignancies in lung nodules as well as general corporate and working capital purposes. The Company may also use proceeds to invest in or acquire businesses or technologies that it believes are complementary, although the Company has no binding agreements with respect to any strategic transactions or acquisitions as of the date of this press release.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any offer, solicitation or sale of these securities in any state or other jurisdiction in which such an offer, solicitation or sale would be unlawful.