1stOncology™: Cancer Intelligence Service – Page 11843 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Lantheus Enters into Strategic Collaboration with CarThera for Use of Microbubbles in Combination with SonoCloud® System for Treatment of Glioblastoma

On December 9, 2019 Lantheus Holdings, Inc. (the "Company") (NASDAQ: LNTH), parent company of Lantheus Medical Imaging, Inc. ("LMI"), a global leader in the development, manufacture and commercialization of innovative diagnostic imaging agents and products, reported it has entered into a strategic commercial supply agreement with CarThera for the use of Lantheus’ microbubbles in combination with SonoCloud, a proprietary implantable device in development for the treatment of recurrent glioblastoma (rGBM) (Press release, Lantheus Medical Imaging, DEC 9, 2019, View Source [SID1234552139]). Gliobastoma is a lethal and devastating form of brain cancer with median survival of 15 months after diagnosis1. The collaboration directly aligns with key Lantheus growth strategies of pursuing new applications for its microbubble franchise and expansion into oncology.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

Under the commercial supply agreement, Lantheus’ microbubbles will be used as a component in CarThera’s SonoCloud System, which uses low-intensity pulsed ultrasound (LIPU) specifically designed to open the blood-brain barrier to facilitate more effective delivery of chemotherapy to tumors. As part of the agreement, CarThera will be responsible for regulatory filings and approvals in the U.S., Europe and rest of world as well as commercialization of SonoCloud. Lantheus will supply its microbubble vials (the ultrasound resonator) and activation devices at a predetermined transfer price. Additionally, Lantheus will receive royalties on the SonoCloud kit product sales upon regulatory approval.

"We are excited to collaborate with CarThera to extend our microbubble franchise into the oncology field to target glioblastoma, an aggressive type of brain cancer with significant unmet medical need," said Mary Anne Heino, President and Chief Executive Officer of Lantheus. "Our collaboration leverages both companies’ strengths to bring novel solutions to the healthcare community. As the use of microbubbles in diagnostic and therapeutic applications gains more interest around the world, our collaboration with CarThera demonstrates our commitment to drive Lantheus’ microbubble into new disease areas with great potential for significant improvement in patient outcomes."

"We are delighted to enter into this collaboration with Lantheus for the development of our SonoCloud ultrasound-based medical device," said Frederic Sottilini, Chief Executive Officer of CarThera. "With Lantheus’ expertise in the field of microbubbles combined with CarThera’s novel and proprietary ultrasound technology, we see the potential for a long-term, highly successful collaboration. We are excited to work with Lantheus to advance our promising SonoCloud technology with the goal of improving treatment and prognosis of patients with glioblastoma, a debilitating, and all too often, fatal disease."

CarThera’s SonoCloud-9 System is currently being evaluated in a Phase IIa clinical trial with a Phase IIb/III pivotal clinical trial to follow. The objective of this trial to evaluate the safety and efficacy of repeated opening of the blood brain barrier using the SonoCloud-9, its next-generation implantable ultrasound device designed to cover the entire tumor and surrounding infiltrative areas. Twenty-one patients will undergo repeated blood brain barrier opening with the SonoCloud-9 prior to infusion of carboplatin at clinical sites in France (Paris, Lyon, Marseille, Angers) and the United-States (MD Anderson Cancer Center in Houston, Northwestern Memorial Hospital in Chicago).

About Glioblastoma

Roughly 12,000 people are diagnosed per year with glioblastoma in the U.S.4, and incidence is growing more than 1% per year5. Worldwide, annual incidence is as high as 5 in 100,000 people, and roughly 225,000 people die from the disease each year.6

The first line treatment for most glioblastoma patients is surgical resection of the tumor. After a healing period from surgery, patients will then typically undergo radiation and chemotherapy treatment cycles.2 The main goal of surgery is to remove as much GBM tumor as possible without impacting surrounding normal brain tissue that is critical for normal neurological function (such as motor skills, speaking and walking ability, etc.). However, GBMs are commonly surrounded by a reservoir of migrating, infiltrating tumor cells that invade surrounding tissue, making it virtually impossible to remove the cancer entirely. Surgery does help to reduce the amount of solid tumor tissue within the brain and thus can reduce intracranial pressure. The surgical debulking of tumor can prolong life and improve the quality of life for patients.2 The treatment of this region surrounding the tumor using chemotherapy is challenging due to the limited penetration of agents into the brain owing to the highly protective blood-brain barrier, a layer of specialized endothelial cells. Research has shown the blood-brain barrier can be accessed using ultrasound in combination with systemic injection of an ultrasonically resonated microbubble.

About the SonoCloud System

Earlier this year, CarThera published results from a Phase I/IIa clinical trial using SonoCloud-1 ultrasound implantable device to open the blood-brain barrier prior to carboplatin chemotherapy in patients with rGBM. Those results from 19 patients, published in the March 19, 2019 edition of journal Clinical Cancer Research, revealed a good safety profile and demonstrated the feasibility and promising potential of the SonoCloud approach. Notably, the 11 rGBM patients who received optimal pressure levels of ultrasound showed a median progression-free survival (PFS) of 4.11 months and a median overall survival (OS) of 12.94 months as compared to those patients who received a suboptimal dosage, in whom median PFS and OS were 2.73 months and 8.64 months, respectively.3

Oncternal Therapeutics Announces Presentation of Clinical Data Update on Cirmtuzumab in Combination with Ibrutinib at 2019 ASH Annual Meeting

On December 9, 2019 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported the presentation of updated interim clinical data from the ongoing Phase 1/2 CIRLL (Cirmtuzumab and Ibrutinib targeting ROR1 for Leukemia and Lymphoma) clinical trial, in which cirmtuzumab, an investigational anti-ROR1 monoclonal antibody, is being evaluated in combination with ibrutinib in patients with chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) (Press release, Oncternal Therapeutics, DEC 9, 2019, View Source [SID1234552138]). The results were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando. A copy of the poster presentation is available online at www.oncternal.com.

Thirty-four patients with CLL who had never been treated with a BTK inhibitor were enrolled in the dose-finding and dose-confirming cohorts of this clinical trial, including 12 treatment-naïve and 22 relapsed/refractory patients, and all 34 were evaluable for efficacy. As of the data cut-off in early November 2019,

Twenty-nine of the 34 patients achieved a response, for an overall best objective response rate of 85%.
One patient achieved a complete response (CR) and remained in remission six months after completion of the trial and discontinuation of all anti-CLL therapy. In addition, three patients met radiographic and hematologic response criteria for Clinical CR, bone marrow biopsy not performed but pending.
Five patients had stable disease.
The total clinical benefit rate was 100%.
None of the patients progressed or died, for a progression-free survival (PFS) of 100% with a median follow-up of 7.4 months.
Patients achieved responses rapidly, with 68% of patients achieving a clinical response by three months on combination therapy.
The rise in leukemic cell counts that is typically seen in the first six months with ibrutinib monotherapy was blunted with the cirmtuzumab plus ibrutinib combination, and leukemic cell counts returned toward baseline and normal levels rapidly.
Twelve patients with relapsed/refractory MCL, eight of whom were evaluable for efficacy, were enrolled in the dose-finding cohort of this trial. As of the data cut-off, five of the eight evaluable patients had achieved a clinical response, for an overall best objective response rate of 63% at a median follow-up of six months. Two patients with aggressive or bulky and heavily pre-treated MCL achieved CR, the longest of which is continuing with the patient on study for over 17 months. In addition, three patients had stable disease, for a total clinical benefit rate of 100%.

Cirmtuzumab as a single agent has been very well tolerated in this study. The combination of cirmtuzumab plus ibrutinib has also been well tolerated, with adverse events consistent with those reported for ibrutinib alone. There have been no dose limiting toxicities and no serious adverse events attributed to cirmtuzumab alone.

Genetic analysis of CLL cells from three patients showed pre-treatment transcriptome profiles associated with a stemness signature and NF-kB-driven inflammation. Both genetic signatures were reversed in these patients following cirmtuzumab treatment.

"It is exciting to see that cirmtuzumab in combination with ibrutinib continues to be well tolerated and has demonstrated 100% progression-free survival in patients with CLL, as well as encouraging early signals of efficacy in patients with MCL," said Michael Choi, M.D., Associate Clinical Professor of Medicine in the Division of Hematology-Oncology at University of California San Diego School of Medicine, who is the lead investigator for the CIRLL clinical trial.

The CIRLL clinical trial is supported by a grant from the California Institute for Regenerative Medicine (CIRM) and is being conducted in collaboration with the UC San Diego School of Medicine.

"We are encouraged by the evidence of clinical activity and the safety data demonstrated by cirmtuzumab in the ongoing CIRLL clinical trial. We continue to be excited about its potential for the treatment of patients with ROR1-expressing cancers, including CLL, MCL, Her2-negative breast cancer and other solid tumors," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO.

About the CIRLL Clinical Trial

The CIRLL clinical trial (CIRM-0001) is a Phase 1/2 trial evaluating cirmtuzumab in combination with ibrutinib in separate groups of patients with chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL). Part 1 of the clinical trial was a Phase 1 dose-finding cohort designed to determine the Phase 2 dose, or recommended dosing regimen (RDR). Part 2 is a Phase 1b expansion cohort to confirm the RDR. Part 3 of the study, which is now open for enrollment, is a Phase 2 study in which approximately 90 patients with CLL will be randomized to receive either ibrutinib alone or ibrutinib plus cirmtuzumab, with a primary endpoint of complete response rate. Additional information about the CIRM-0001 clinical trial and other clinical trials of cirmtuzumab may be accessed at ClinicalTrials.gov.

About Cirmtuzumab

Cirmtuzumab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Cirmtuzumab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of CLL and MCL, in a collaboration with the University of California San Diego School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, an investigator-initiated Phase 1 clinical trial of cirmtuzumab in combination with paclitaxel for women with metastatic breast cancer is being conducted at the UC San Diego School of Medicine. CIRM has also provided funding to support development programs for cirmtuzumab and a CAR-T therapy that targets ROR1, which is currently in preclinical development as a potential treatment for hematologic cancers and solid tumors.

ROR1 is a potentially attractive target for cancer therapy because it is an oncofetal antigen – a protein that confers a survival and fitness advantage when reactivated and expressed by tumor cells. When expressed by hematologic malignancies such as CLL and MCL, ROR1 acts as a receptor for the tumor growth factor Wnt5a. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to inhibiting Wnt5a activation, specifically targeting ROR1 expressing tumors. This led to the development of cirmtuzumab that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when cirmtuzumab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. Cirmtuzumab is in clinical development and has not been approved by the U.S. Food and Drug Administration for any indication.

Magenta Therapeutics Demonstrates First-ever Successful Gene Therapy Transplant Without Chemotherapy in Primates Using a Single Dose of Antibody-drug Conjugate

On December 9, 2019 Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of immune reset to more patients, reported that new results from its CD117-ADC patient preparation program were presented at the 61st Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Magenta Therapeutics, DEC 9, 2019, View Source [SID1234552136]). These results, which were highlighted in an oral presentation at ASH (Free ASH Whitepaper) by John Tisdale, M.D., Director, Molecular and Clinical Hematology Section, National Institutes of Health, showed the first-ever successful transplant of gene-modified cells in non-human primates using a targeted, single-agent antibody-drug conjugate (ADC), without the use of chemotherapy or radiation.

"Today’s conditioning regimens involve high doses of chemotherapy, often paired with radiation, to remove the disease-causing cells. As a result, patients undergoing gene therapy or stem cell transplant are all faced with a difficult choice: whether to endure severe toxicity and risk infertility and cancer for the chance for a cure. Magenta’s portfolio of targeted ADCs represents an extremely promising new option to prepare patients for gene therapy or transplant with no need for toxic chemotherapy or radiation," said Dr. Tisdale. "The results presented today show that a single dose of single agent CD117-ADC achieves the same level of depletion as four doses of busulfan chemotherapy to enable successful engraftment and persistence of stem cells modified with the β-globin gene, the gene that causes sickle cell disease and β-thalassemia when mutated. Importantly, the animals undergoing preparation with CD117-ADC showed none of the damaging toxicities associated with busulfan conditioning."

"Magenta is the only company with the people, platforms and a product engine committed to comprehensively transforming immune and blood system reset, which includes revolutionizing the toxic methods that are used to prepare patients for gene therapy and transplant today." said Jason Gardner, D.Phil., Chief Executive Officer and President, Magenta Therapeutics. "The gene therapy field has learned that higher levels of stem cell depletion, which meant higher doses of busulfan, were needed to ensure long-term engraftment of the gene-modified cells and persistence of gene therapy. Across all the modalities we have tested, we have seen that ADCs are most effective at achieving these high levels of stem cell depletion without chemotherapy to enable engraftment and long-term durability of the transplant. Today’s impressive results provide important validation of the ADC approach as well as the CD117 target for patient preparation and underscore Magenta’s leadership in the field of conditioning."

Results from the CD117-ADC Patient Preparation Program

Title: A Single Dose of CD117 Antibody Drug Conjugate Enables Autologous Gene-Modified Hematopoietic Stem Cell Transplant (Gene Therapy) in Nonhuman Primates (Abstract #610)
Presenter: John Tisdale, M.D., Director, Molecular and Clinical Hematology Section, National Institutes of Health, Bethesda, Md.

Magenta’s most advanced patient preparation program, CD117-ADC, targets CD117, a protein expressed on hematopoietic stem cells. CD117-ADC is designed to remove the genetically mutated cells in the bone marrow that cause certain genetic diseases, such as sickle cell disease, enabling curative stem cell transplant or gene therapy.

Results presented by Dr. Tisdale showed:

A single dose of a tool CD117-ADC fully depleted human hematopoietic stem cells in humanized mouse models.
A single dose of CD117-ADC selectively depleted hematopoietic stem cells in non-human primates, while sparing immune cells, which are important for recovery following transplant.
CD117-ADC was engineered to have a fast half-life to clear the body quickly and enabled transplant of the gene-modified cells within days of dosing in non-human primates.
A single dose of CD117-ADC in non-human primates enabled successful transplant and engraftment of hematopoietic stem cells modified with a lentiviral vector encoding the β-globin gene, the gene that causes sickle cell disease and β-thalassemia.
Vector copy number was stable beyond three months, the longest time point in the study, suggesting that the gene-modified cells persisted in the body. This was comparable to historical data with multiple doses of busulfan conditioning.
CD117-ADC was well tolerated in non-human primates with no evidence of the often severe side effects seen with busulfan conditioning, including veno-occlusive disease, weight loss, diarrhea, mucositis, vomiting, pulmonary fibrosis or seizures.
No ADC-related blood chemistry changes outside normal range were observed.
These proof-of-concept studies validate the use of CD117-ADC for targeted stem cell depletion prior to transplant and support its use as a new conditioning agent for gene therapy and stem cell transplant without toxic chemotherapy or radiation.

IONTAS Antibody Enters Clinical Trial for Use in the Treatment of B Cell Acute Lymphoblastic Leukemia

On December 9, 2019 IONTAS Limited (IONTAS), a leader in the discovery and optimisation of fully human antibodies, has been informed that International Biotechnology Center (IBC) Generium, a leading Russian biopharmaceutical company, focused on developing and commercialising pharmaceutical products for the treatment of orphan diseases and cancer, reported that it has received approval from the Russian Health Authorities to initiate clinical trials with its CD3/CD19 bispecific antibody for the treatment of B-Cell Acute Lymphoblastic Leukemia (ALL) (Press release, Iontas, DEC 9, 2019, View Source [SID1234552135]). This is the first IBC Generium drug candidate developed using IONTAS technology, which was approved for clinical trials. IBC Generium and IONTAS worked together to generate the anti-CD3 component of the bispecific molecule. This approval reflects the quality of antibodies generated and expertise within IBC Generium to reach this important clinical milestone. Following on from this trial it is anticipated that further clinical trials incorporating IONTAS antibodies will be driven forward by clients of IONTAS in the coming few years.

Dr John McCafferty, CEO and Founder of IONTAS, said: "We are very proud of our involvement in this project and delighted that IBC Generium has achieved this important landmark. We are hopeful for success in this initial trial and are excited by the prospect of our anti-CD3 antibody contributing more broadly to the armoury of new and innovative cancer treatments."

Dr Ravil Khamitov, CEO of IBC Generium, said: "IONTAS was selected because of its robust track record and technical know-how. We were confident IONTAS would deliver antibodies suitable for use in our bispecific programs and were not disappointed. This trial is vindication of that confidence. We look forward to a successful clinical trial and further success with other antibodies developed with IONTAS."

Dr Neil Butt, CBO and Dr John McCafferty, CEO and Founder of IONTAS, will attend 38th Annual J.P.Morgan Healthcare Conference (San Francisco, CA) from January 13 – 16 2020. Dr Neil Butt will be at Antibody Engineering and Therapeutics (San Diego, CA) from 9 – 13 December 2019.

Immunocore announces dosing of first patient with third ImmTAC® bispecific

On December 9, 2019 Immunocore Limited, a leading T Cell Receptor (TCR) biotechnology company, reported the start of the first-in-human clinical trial of IMC-C103C, the third bispecific developed using the company’s innovative ImmTAC technology platform (Press release, Immunocore, DEC 9, 2019, View Source [SID1234552134]). IMC-C103C is focused on targeting tumours that express the protein MAGE-A4 (Melanoma-Associated Antigen A4) and is being developed in partnership with Genentech, a member of the Roche Group.

The trial (IMC-C103C-101) is designed to study the safety and preliminary activity of IMC-C103C as a monotherapy and in combination with atezolizumab (Tecentriq) in patients with MAGE-A4-expressing cancers.

David Berman, Head of Research and Development at Immunocore, commented: "We have now brought our third TCR- engineered bispecific ImmTAC into the clinic. IMC-C103C is designed to re-direct T cells to attack MAGE-A4 expressing tumours and we’re pleased to be moving its clinical development forward in partnership with Genentech."