On June 16, 2021 Servier, a growing leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported that Clinical Cancer Research has published data from its Phase I study evaluating single-agent vorasidenib in isocitrate dehydrogenase (IDH) mutant advanced solid tumors, including low-grade glioma (Press release, Servier, JUN 16, 2021, View Source [SID1234584082]). Vorasidenib is an investigational, oral, selective, brain-penetrant dual inhibitor of mutant IDH1 and IDH2 enzymes.

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In the first-in-human study (NCT02481154), vorasidenib demonstrated both a favorable safety profile at doses <100 mg once daily and preliminary clinical activity in recurrent or progressive IDH1/2 mutant low-grade glioma. The study data demonstrated a median progression-free survival of 36.8 months (3.1 years) [95% confidence interval (CI), 11.2–40.8 months] for patients with nonenhancing low-grade glioma. The protocol-defined objective response rate per Response Assessment in Neuro-Oncology criteria for LGG (RANO-LGG) in patients with nonenhancing low-grade glioma was 18% (one partial response, three minor responses). Exploratory evaluation of tumor volumes showed sustained tumor shrinkage in multiple patients with nonenhancing low-grade glioma.

"Given the toxicities associated with chemotherapy and radiation, there remains a significant unmet need to improve treatment options for patients living with IDH mutant low-grade glioma," said Tim Cloughesy, M.D., David Geffen School of Medicine, Department of Neurology, University of California, Los Angeles, an investigator for the Phase 1 study. "These early results reinforce the potential benefit of vorasidenib and the further exploration of more targeted therapies."

Mutations in the metabolic enzymes IDH1/2 occur in up to approximately 80% of patients with low-grade gliomas. Standard treatment of low-grade gliomas includes tumor resection, followed by radiation and chemotherapy as appropriate. This treatment is not curative and current therapy is associated with short- and long-term toxicity, with most patients experiencing disease recurrence and progression to a higher tumor grade. In this study, vorasidenib demonstrated a favorable safety profile. Dose-limiting toxicities of elevated transaminases occurred at doses ≥100 mg and were reversible.

"We are excited to announce the publication of our first clinical data manuscript in glioma in Clinical Cancer Research, underscoring the potential benefit of vorasidenib in IDH mutant low-grade glioma," said Susan Pandya, M.D., Vice President, Clinical Development, Head of Cancer Metabolism Global Development, Servier Pharmaceuticals. "These data provide further support for our registration-enabling Phase 3 INDIGO study evaluating the activity of vorasidenib at an early stage of the disease where delaying the need for more aggressive treatments could provide a meaningful benefit to patients."

Vorasidenib is currently being evaluated in the registration-enabling Phase 3 INDIGO study as a potential treatment for patients with residual or recurrent grade 2 low-grade glioma (NCT04164901).

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Vorasidenib Phase 1 Dose-Escalation Study

Vorasidenib, an investigational, oral, selective, brain-penetrant dual inhibitor of mutant IDH1 and IDH2 enzymes, is being evaluated as a single agent in an ongoing Phase 1 dose-escalation trial in IDH1/2 mutant advanced solid tumors (n=93), including glioma (n=52). Vorasidenib was administered orally, once daily, in 28-day cycles until progression or unacceptable toxicity. Enrollment was completed in June 2017 (NCT02481154).

Vorasidenib INDIGO Phase 3 Study

Vorasidenib, an investigational, oral, selective, brain-penetrant dual inhibitor of mutant IDH1 and IDH2 enzymes, is currently being evaluated in the registration-enabling Phase 3 INDIGO study as a potential treatment for patients with residual or recurrent grade 2 low-grade glioma (NCT04164901).

About Glioma

Glioma presents in varying degrees of tumor aggressiveness, ranging from slower growing (low-grade glioma) to rapidly progressing (high-grade glioma-Glioblastoma Multiforme). Tumor enhancement is an imaging characteristic assessed by magnetic resonance imaging (MRI), and enhancing tumors are more likely to be high-grade.

Common symptoms of glioma include seizures, memory disturbance, sensory impairment and neurologic deficits. The long-term prognosis is poor, and regardless of treatment, the majority of patients with low-grade gliomas will have recurrent disease that will progress over time. Approximately 11,000 low-grade glioma patients are diagnosed annually in the U.S. and EU and approximately 80% have an IDH mutation.

On June 16, 2021 ImmunoGenesis, a clinical-stage biotechnology company developing therapeutics to catalyze effective immune responses in immunologically cold cancers, reported the publication in Clinical Cancer Research of results from a Phase 1 trial of evofosfamide, the only known reducer of solid tumor hypoxia, combined with an immune checkpoint inhibitor, ipilimumab, in patients with advanced cancer (Press release, ImmunoGenesis, JUN 16, 2021, View Source [SID1234584081]). The journal article, "A Phase 1 Dose Escalation Study to Evaluate the Safety and Tolerability of Evofosfamide in Combination with Ipilimumab in Advanced Solid Malignancies," highlights an overall response rate of 17% and a disease control rate of 83% across four dose levels in 21 heavily pre-treated patients. In addition, a clear biomarker picture emerged with pre-existing immune gene signatures correlating with response to therapy and hypermetabolic signatures predicting progression. Responders also showed improved cellular signatures of anti-tumor immunity.

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"A hostile tumor metabolism is a major source of immune resistance in certain tumors," said James Barlow, ImmunoGenesis President and CEO. "Evofosfamide, with the demonstrated ability to reduce tumor hypoxia, can be a critical component of facilitating immunotherapy efficacy in these tumors. With these compelling results in hand, we look forward to advancing our development pipeline."

"Along with others in the field, I had identified tumor hypoxia as a barrier to effective tumor immunity in certain tumors," said Michael Curran, PhD, founder of ImmunoGenesis. "These exciting Phase 1 data support preclinical observations in which evofosfamide reversed tumor hypoxia and facilitated the efficacy of checkpoint inhibition. The efficacy of the combination in these heavily pre-treated patients appears superior to checkpoint monotherapy and provides strong rationale for the use of evofosfamide as a tumor conditioning agent."

The study was led at The University of Texas MD Anderson Cancer Center by Curran, Associate Professor of Immunology and David S. Hong, M.D., Professor of Investigational Cancer Therapeutics. Dr. Curran has a personal financial relationship with ImmunoGenesis, which is managed and monitored by the MD Anderson Conflict of Interest Committee.

About the Phase 1 Study
The Phase 1 (NCT03098160), dose-escalation study tested evofosfamide in combination with ipilimumab administered in four three-week cycles in heavily pre-treated patients with castration-resistant prostate cancer, advanced pancreatic cancer, immunotherapy-resistant melanoma, and advanced HPV-negative head and neck cancer. The combination regimen was well-tolerated, with most drug–related-adverse events being grade 1–2. There were no unexpected safety signals.

About Evofosfamide
Evofosfamide is a 2-nitroimidazole prodrug of the cytotoxin bromo-isophosphoramide mustard (Br-IPM) originally developed as a hypoxia-activated prodrug. Through his research, Dr. Curran discovered that evofosfamide can reduce hypoxia in solid tumors. In pre-clinical models, evofosfamide restored T cell function and synergized with checkpoint inhibition. ImmunoGenesis is developing evofosfamide as a hypoxia-reversal agent that can condition tumors to respond to checkpoint inhibition.

On June 16, 2021 Harbour BioMed (HKEX: 02142) reported that it has entered into a multi-year, multifaceted research collaboration agreement with Dana-Farber Cancer Institute to co-develop novel biotherapies in cancer treatment(Press release, Harbour BioMed, JUN 16, 2021, View Source [SID1234584080]).

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Harbour BioMed scientists and Dana-Farber researchers will be working together to develop novel oncologic drugs, including bispecific antibodies and CAR-T cell products. In recent years, bispecific antibodies and CAR-T cell therapies are both considered as the next-generation solutions in the tumor immunology field. For their ability to engage two different targets, bispecific antibodies are expected to extend the possibilities of monoclonal antibody (mAb) therapeutics, and CAR-T cell therapy is an innovative immunotherapy that uses specially altered T-cells to redirect them to target cancer cells.

This strategic collaboration will leverage Harbour BioMed’s transgenic Harbour Mice platform with Dana-Farber’s expertise in CAR-T cell development and basic oncology research to generate novel biotherapies.

Harbour BioMed’s antibody technology platforms – Harbour Mice, which is based on two proprietary transgenic mouse platforms will be utilized to generate human therapeutic antibodies. The platforms have broad potential for generating both conventional as well as next-generation biologics, such as bi- and multi-specifics, CAR-Ts or VH domain-derived products that are fully human, affinity matured with excellent solubility and developability.

"We are delighted to initiate this collaboration with Harbour BioMed. The complementary technology and expertise between Harbour and DFCI will dramatically shorten the interval from novel discovery to developing optimized antibody and cellular therapies for clinical translation," said Dr. Eric Smith, Laboratory Principal Investigator & Director of Translational Research for Immune Effector Cell Therapies at Dana-Farber Cancer Institute.

"The collaboration with world renowned Dana-Farber Cancer Institute demonstrates HBM’s commitment to developing novel medicines and fostering fast-track innovative research. I believe this collaboration will be ultimately translated into better treatments for cancer patients," said Jingsong Wang, Founder, Chairman & Chief Executive Officer of HBM.

On June 16, 2021 Marker Therapeutics, a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported that its Chief Financial Officer, Anthony H. Kim, will present at the upcoming virtual Raymond James Human Health Innovation Conference on Monday, June 21, 2021 at 9:20 a.m. ET (Press release, Marker Therapeutics, JUN 16, 2021, View Source [SID1234584079]).

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A live webcast of the presentation will be accessible from the Investors section of the company’s website at markertherapeutics.com and will be available for replay following the event.

On June 16, 2021 A1 Medical Imaging’s Chief Operating Officer, Marilyn Radakovic, applauded recent research that indicates magnetic resonance imaging (MRI) is effective in detecting interval breast cancers in women with a prior history of the disease (Press release, A1 Medical Imaging, JUN 16, 2021, View Source [SID1234584078]).

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The research that was published June 8, 2021, in the Radiology journal concluded that breast MRI has been shown to improve the early detection of recurrent breast cancers that may be missed by mammography.

The study took place between January 2008 and March 2019 and involved 2,809 women with a median age of 47 years who had undergone surgery because of breast cancer. In all, 6,603 MRI examinations were conducted.

"According to the report, the purpose of the research was to evaluate the screening of breast MRI in women with a personal history of breast cancer who might be at more risk for what’s known as interval breast cancers or IBC," Radakovic stated. "IBC is the cancer detected after a normal screening mammogram, but before the next scheduled mammogram."

Mammograms are low-dose X-rays of the breast. Regular mammograms are recommended to find breast cancer early, when treatment is most successful. However, mammograms may not be the best option for women who are at high risk.

A breast MRI is a noninvasive technology that uses strong magnets instead of radiation to make very detailed, cross-sectional pictures of the breast. It is much more sensitive than mammography and can find invasive breast cancers sooner than mammograms. It can also rule out abnormalities that appear suspicious on a mammogram.

Peter Solodko, A1 Medical Imaging’s Chief Executive Officer, commented, "This research indicates that breast MRIs can detect early stages of cancer better than mammography in women with a past history of breast cancer."

Radakovic added, "This research confirms the effectiveness of breast MRIs and provides encouraging hope for women who are at high risk of recurring cancer."

A1 Medical Imaging has open MRI centers throughout Florida and in Georgia and provides breast MRI screenings at its Aventura, Pembroke Pines, Plantation and Orange Park locations in Florida. Visit www.A1mri.com to learn more.