On December 16, 2019 GlaxoSmithKline reported treatment with the investigational single-agent belantamab mafodotin resulted in a clinically meaningful 31% overall response rate (ORR) with the 2.5 mg/kg regimen in patients with heavily pre-treated multiple myeloma (Press release, GlaxoSmithKline, DEC 16, 2019, View Source [SID1234552397]). Patients in the trial received a median of seven prior lines of treatment, were refractory to an immunomodulatory drug and a proteasome inhibitor and were refractory and/or intolerant to an anti-CD38 antibody. The median duration of response has not been reached at six months of follow-up.

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Full results from the DREAMM-2 (DRiving Excellence in Approaches to Multiple Myeloma) study of belantamab mafodotin were published today in The Lancet Oncology. GSK also confirmed submission of a Biologics License Application to the US Food and Drug Administration (FDA) seeking approval of belantamab mafodotin for the treatment of patients with relapsed or refractory multiple myeloma whose prior therapy included an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. Belantamab mafodotin is not currently approved for use anywhere in the world.

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK said: "Patients with multiple myeloma whose disease has progressed despite currently available therapy have limited options and poor outcomes. Data from the DREAMM-2 study show that, if approved, belantamab mafodotin could offer an important new treatment option for these patients."

DREAMM-2 is an open label study of belantamab mafodotin, a humanised, immunoconjugate against B-cell maturation antigen (BCMA).[i] Patients in the trial had actively progressing multiple myeloma that had worsened despite current standard of care and were randomised to two arms to receive either 2.5 mg/kg or 3.4 mg/kg belantamab mafodotin every three weeks. Overall, patients in DREAMM-2 had more advanced disease, poorer prognosis and performance status and also had a greater number of prior lines of therapy in comparison with patients in DREAMM-1, the first time in human study of belantamab mafodotin.

Dr Sagar Lonial, MD, Chief Medical Officer, Winship Cancer Institute of Emory University, Chair of Emory Department of Hematology and Medical Oncology and Principal Investigator for DREAMM-2, said: "Each day in my practice, I see patients who would benefit from additional therapeutic options because their disease has advanced and is no longer responding to available treatments. In recent years, BCMA has become one of the most promising targets in multiple myeloma research. The data published today from DREAMM-2 not only reinforce the significance of BCMA as a potentially viable target, but also underscore the potential of belantamab mafodotin, if approved, as a practical treatment option in this patient population."

The results demonstrated in DREAMM-2 were consistent with those observed in a similar subset of patients in the DREAMM-1 study. Based on these data, GSK is moving forward with a US FDA submission seeking approval of the 2.5 mg/kg dose. If approved, belantamab mafodotin will be the first anti-BCMA agent available in the US.

Thirty of the 97 patients (31%) in the 2.5 mg/kg cohort achieved an overall response. Of these responders, 18 patients achieved a very good partial response or better, including three patients with stringent complete or complete responses. In addition, overall survival in patients achieving a response was not reached in the six month follow-up period.

The safety and tolerability profile was consistent with previously reported data on belantamab mafodotin. The three most commonly reported Grade 3 or 4 adverse events in the 2.5 mg/kg arm were keratopathy (27%), thrombocytopenia (20%) and anaemia (20%). Keratopathy is characterized as changes in the corneal epithelium as seen on eye examination which can manifest with or without symptoms. Corneal events leading to treatment discontinuation affected 1% of patients in the 2.5 mg/kg cohort.

Additional studies are testing the effect of belantamab mafodotin as third-line monotherapy in relapsed/refractory multiple myeloma and in combination with standard and novel treatments in the first and second line setting as part of the broader DREAMM clinical development programme.

In 2017, GSK2857916 was granted Breakthrough Therapy designation from the US FDA and PRIME designation from the European Medicines Agency.

In the US, an expanded access program for belantamab mafodotin is available to eligible patients with multiple myeloma. For patients to be considered for enrollment in the programme, they must be assessed according to specific inclusion and exclusion criteria by their treating physician. Additional information about the expanded access protocol can be found on ClinicalTrials.gov (NCT03763370).

About multiple myeloma
Multiple myeloma is the second most common blood cancer and is generally considered treatable, but not curable.[ii] Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.[iii]

About B-cell maturation antigen (BCMA)
The normal function of BCMA is to promote plasma cell survival by transduction of signals from two known ligands, BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). This pathway has been shown to be important for myeloma cell growth and survival. BCMA expression is limited to B cells at later stages of development. BCMA is expressed at varying levels in myeloma patients and BCMA membrane expression is universally detected in myeloma cell lines.[iv]

About the DREAMM clinical trial programme for belantamab mafodotin (GSK2857916)
Belantamab mafodotin is an investigational immunoconjugate comprising a humanised anti-B cell maturation antigen (BCMA) monoclonal antibody conjugated to the cytotoxic agent auristatin F via non-cleavable linker. The drug linker technology is licensed from Seattle Genetics; monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa.

Trial Name

GSK ID/NCT ID

Status

Design

DREAMM-1

117159/ NCT02064387

Completed

A Phase I Open-label Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical Activity of Belantamab Mafodotin (GSK2857916) in Subjects with Relapsed/Refractory Multiple Myeloma and Other Advanced Hematologic Malignancies Expressing BCMA

DREAMM-2

205678/ NCT03525678

Active, not recruiting

A Phase II Study to Investigate the Efficacy and Safety of Two Doses of Belantamab Mafodotin (GSK2857916) in Subjects with Relapsed/Refractory Multiple Myeloma Who are Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed Prior Treatment with an Anti-CD38 Antibody

DREAMM-3

207495

Planned

A Phase III Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) Compared to Pomalidomide plus low-dose Dexamethasone (Pom/Dex) in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-4

205207/ NCT03848845

Recruiting

A Phase I/II Single Arm Open-Label Study to Explore Safety and Clinical Activity of Belantamab Mafodotin (GSK2857916) Administered in Combination with Pembrolizumab in Subjects with Relapsed/Refractory Multiple Myeloma

DREAMM-5

208887/

NCT04126200

Recruiting

A Phase I/II, Randomized, Open-label Platform Study of Belantamab Mafodotin (GSK2857916) with Innovative Combination Anti-Cancer Treatments in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-6

207497/ NCT03544281

Recruiting

A Phase I/II Randomized Study to Evaluate Safety, Tolerability and Clinical Activity of Belantamab Mafodotin (GSK2857916) Administered in Combination with Lenalidomide plus Dexamethasone (Arm A), or in Combination with Bortezomib plus Dexamethasone (Arm B) in Subjects with Relapsed/Refractory Multiple Myeloma

DREAMM-7

207503

Planned

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Bortezomib plus Dexamethasone versus Daratumumab, Bortezomib, and Dexamethasone in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-8

207499

Planned

A Phase III, Multicentre, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) in Combination with Pomalidomide plus Low-Dose Dexamethasone (BPd) versus Pomalidomide plus Bortezomib and Low-Dose Dexamethasone (PVd) in Participants with Relapsed/Refractory Multiple Myeloma

DREAMM-9

209664/ NCT04091126

Planned

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Bortezomib plus Lenalidomide and Low-Dose Dexamethasone (VRd) vs. VRd in Participants with Newly Diagnosed Multiple Myeloma who are Ineligible for Transplant

DREAMM-10

207500

Planned

A Phase III Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with a Novel Agent versus SoC

ISS / GSK Co-Sponsored Study

209418/ NCT03715478

Recruiting

A Phase I/II Dose-escalation and Dose-expansion Study of Belantamab Mafodotin (GSK2857916) Administered in Combination with Pomalidomide plus Low-dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma Who Have Received Two or More Prior Lines of Therapy That Must Have Included Lenalidomide and a Proteasome Inhibitor

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics, and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On December 16, 2019 Zimmer Biomet Holdings, Inc. (NYSE and SIX: ZBH), a global leader in musculoskeletal healthcare, reported that its Board of Directors has approved the payment of a quarterly cash dividend to stockholders for the fourth quarter of 2019 (Press release, Zimmer Holdings, DEC 16, 2019, View Source [SID1234552413]).

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The cash dividend of $0.24 per share is payable on January 31, 2020 to stockholders of record as of the close of business on December 27, 2019.

On December 16, 2019 Astellas Pharma Inc. (TSE:4503, Headquarters: Tokyo, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that it has commenced, through its indirect, wholly-owned subsidiary Asilomar Acquisition Corp. ("Asilomar"), a tender offer ("Tender Offer") for all of the issued and outstanding shares of common stock of Audentes Therapeutics, Inc. (NASDAQ: BOLD, Headquarters: San Francisco, Chairman and CEO: Matthew R. Patterson, "Audentes") for a price of US$60.00 per share, net to the seller in cash, on December 16, 2019, New York City time (Press release, Astellas, DEC 16, 2019, View Source [SID1234552380]). The Tender Offer is scheduled to expire at 12:00 midnight, New York City time, at the end of the day on January 14, 2020, unless extended or earlier terminated.

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The Tender Offer was commenced pursuant to the definitive agreement dated December 2, 2019, by and among Astellas, Asilomar and Audentes, and promptly upon successful completion of the Tender Offer, Asilomar will be merged into Audentes, with Audentes surviving the merger as a subsidiary of Astellas.

On December 16, 2019 Immune Therapeutics, Inc. (OTCQB: IMUN) ("Immune", "IMUN" or the "Company") and Aletheia Therapeutics Corp. ("Aletheia"), a privately held development-stage oncology therapeutics company, reported that Immune will acquire Aletheia in an all-stock transaction (Press release, Immune Therapeutics, DEC 16, 2019, View Source [SID1234552398]). Pursuant to completion of a definitive agreement, Immune will acquire all of the outstanding shares of Aletheia in exchange for Immune common stock . In connection with the acquisition, the Aletheia management team will join the leadership of the combined Company as well as selected Board members of Aletheia.

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Over the past several years researchers have demonstrated that cancer is inherently heterogenous and a single tumor can have up to one hundred different cell phenotypes. This knowledge has led to a new approach in cancer therapy in that targeting several different biological targets in cancer provides for better efficacy and lower toxicity. Specifically, a combination of drugs that each target an independent critical pathway in cancer growth is becoming widely recognized as the future of cancer treatment. The combined company will be focused on developing and commercializing precision cancer therapies by simultaneously targeting two or more of the following biological targets depending on the make-up of a patients’ cancer: DNA repair, T-cell activation, metabolic dysfunction, angiogenesis, apoptosis or inflammation.

"With this acquisition we will be able to develop a diverse platform of therapies that target multiple critical biological pathways that will be designed for an individual’s cancer," said Michael Handley, chief executive officer and president, Immune Therapeutics. "The combination of Aletheia’s diverse oncology product pipeline with Immune’s Lodonal and MENK product candidates will create an industry leading oncology company."

"Following an extensive evaluation and diligence process, the Immune Board of Directors concluded that the acquisition of Aletheia, with a strong platform technology, seasoned leadership team, and compelling clinical development plan, offered an excellent opportunity to create shareholder value for Immune," stated Dr. Roscoe Moore, the chairman of Immunes Board of Directors. "We believe Aletheia represents an attractive acquisition target for Immune, offering a novel approach to creating precision therapies for cancer patients with unmet medical needs."

Under the initial terms announced today, Immune, through a subsidiary, will initiate an offer to acquire all outstanding shares of Aletheia. The closing of the offer will be subject to certain conditions, including completing due diligence, the employment of the Aletheia management team to Immune management team and the assignment of all intellectual property to Immune. Furthermore, Aletheia has signed definitive stock purchase agreement with an investor group for $25 million that should fund before the end of the year. Once the acquisition is complete Aletheia and Immune will be funded with sufficient capital to execute on the product development strategy in 2020. The acquisition is expected to close early in the first quarter of 2020.

On December 16, 2019 Sysmex Inostics reported that new data presented by Dr. Ben Ho Park, Professor of Medicine and Director of Precision Oncology at Vanderbilt University and colleagues at the recent San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas demonstrated a potential utility for monitoring tumor-specific mutations (TSMs) in the circulation of early stage triple-negative breast cancer patients (Press release, Sysmex Inostics, DEC 16, 2019, View Source [SID1234552414]). The investigators utilized Sysmex Inostics’ highly sensitive SafeSEQ technology to detect rare variants down to 0.05% mutant allele fraction (MAF) to explore the rate of detection of ctDNA variants independent of the need for a tissue biopsy.

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This initial data was generated as a pilot investigation as part of the PREDICT DNA trial ("Pathologic Response Evaluation and Detection In Circulating Tumor DNA"), the first prospective, multi-center study designed to verify cell-free circulating tumor DNA (ctDNA) as a biomarker for treatment response and recurrence in early stage breast cancer, with the primary aim of determining the negative predictive value of a negative ctDNA result after neoadjuvant therapy for the achievement of pathologic complete response. Essentially the trial measures whether patients who undergo neoadjuvant chemotherapy to treat tumors prior to surgery still have ctDNA in their blood after the therapy but before surgery. Dr. Park shared, "We give chemotherapy to early stage breast cancer patients and probably 70 percent of those patients don’t need it, but we generally can’t define who has micro-metastatic disease and who doesn’t." The PREDICT DNA trial is aiming to understand whether ultrasensitive next-generation sequencing with a SafeSEQ targeted cancer mutation panel can identify and monitor ctDNA of early-stage breast cancer patients to more precisely administer neoadjuvant therapy and surgery in newly diagnosed patients.

A total of 228 patients with Stage II and III triple-negative or HER2-positive breast cancer have been enrolled at 22 sites, of which 77 with matched pre- and post-neoadjuvant therapy samples were available at the time of the pilot study. Using SafeSEQ, tumor-specific mutations were identified in 48% (37/77) of the pre therapy samples, of which 89% had detectable plasma TP53 mutations, 11% had PIK3CA mutations, and 11% had co-occurring TP53 and PIK3CA mutations. A cohort of patient plasma specimens underwent orthogonal testing with OncoBEAM digital PCR technology, with 100% concordance of results with SafeSEQ.

The authors of the study concluded that SafeSEQ’s ultrasensitive detection of ctDNA has ‘significant clinical implications as an affordable and non-invasive first-pass assay in patients with sparse tumor biopsy tissue’. This preliminary data also demonstrates clinical feasibility of identifying tumor-specific mutations in individuals using minimally-invasive liquid biopsy before neoadjuvant treatment for personalized disease response monitoring without the need for biopsy tissue for NGS analysis.

"There is a paramount need for prospective studies using liquid biopsy," said Dr. Ben Ho Park, Professor of Medicine and Director of Precision Oncology, Vanderbilt University Medical Center. "These exciting preliminary results from the PREDICT DNA Trial represent an important first step in understanding the role of liquid biopsy testing for the management of early stage breast cancer and helping the medical community map out a path to make precision medicine a reality for patients across the continuum of care."

Presentation Details: Saturday 14 December 2019 7am – 9am, Poster Session 6, P6-10-05

Hunter, N. et al (2019) Pathologic Response Evaluation and Detection In Circulating Tumor DNA (PREDICT DNA): Initial results piloting a tissue-biopsy independent method of identifying and monitoring tumor-specific mutations in early stage breast cancer: TBCRC 040 Presented at the San Antonio Breast Cancer Symposium in San Antonio, Texas. ClinicalTrials.gov Identifier: NCT02743910

This work supported by the Translational Breast Cancer Research Consortium.