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GSK presents new data from the GARNET study demonstrating potential of dostarlimab to treat a subset of women with recurrent or advanced endometrial cancer

On April 23, 2020 GlaxoSmithKline plc reported data from an updated analysis of the GARNET trial, which demonstrated that dostarlimab, an investigational anti-programmed death-1 (PD-1) monoclonal antibody, provided clinically meaningful results in women with recurrent or advanced mismatch repair-deficient (dMMR) endometrial cancer who progressed on or after a platinum-based regimen (Press release, GlaxoSmithKline, APR 23, 2020, View Source [SID1234556530]).

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This updated analysis included patients with dMMR endometrial cancer who had measurable disease at baseline and ≥6 months of follow-up by the data cutoff (n=71). Patients received 500 mg of dostarlimab once every three weeks for four doses, followed by 1,000 mg once every six weeks until disease progression. The primary endpoints were confirmed objective response rate (ORR) and duration of response (DoR), as assessed against RECIST v 1.1 by blinded independent central review. GARNET is the largest dataset evaluating an anti-PD-1 in endometrial cancer.

Treatment with dostarlimab showed an ORR of 42% (95% CI; 31-55) and a disease control rate of 58% (95% CI; 45-69). Overall, 13% of patients had a complete response and 30% of patients had a partial response. At the time of data cutoff, with a median follow up of 11.2 months, the median DOR had not been reached (1.87+ to 19.61+ months).

Dr. Axel Hoos, Senior Vice President and Head Oncology R&D, GSK said: "We are committed to developing medicines for patients who face high unmet medical need. We believe in the clinical potential of dostarlimab for women with advanced or recurrent dMMR endometrial cancer who urgently need additional treatment options for this incurable disease."

Dr. Ana Oaknin, Head of the Gynaecologic Cancer Program at Vall d’Hebron Institute of Oncology, Barcelona, and primary investigator for GARNET said: "There are limited treatment options for women with advanced or recurrent endometrial cancer, and prognosis of these patients is poor. The results observed in the GARNET trial indicate the potential of dostarlimab to offer a new treatment option for women with this challenging disease."

The safety population included all patients with dMMR endometrial cancer who received at least one dose of dostarlimab (n=104). Results showed that dostarlimab was well tolerated with a low discontinuation rate (2%) due to treatment-related adverse events (TRAEs), consistent with the safety profiles of other anti-PD-1 therapies. The most commonly reported TRAEs were asthenia (15%), diarrhoea (15%), fatigue (14%), and nausea (13%). No deaths associated with dostarlimab were reported in the study.

Dostarlimab is not currently approved for use anywhere in the world.

About GARNET
The ongoing phase I GARNET trial is evaluating dostarlimab as monotherapy in patients with advanced solid tumours. Part 2B of the study includes five expansion cohorts: dMMR/MSI-H endometrial cancer (cohort A1), mismatch repair proficient endometrial cancer (cohort A2), non-small cell lung cancer (cohort E), dMMR/MSI-H non-endometrial cancer (cohort F), and platinum-resistant ovarian cancer without BRCA mutations (cohort G). GARNET is still enrolling patients.[1,2]

About Dostarlimab
Dostarlimab is an investigational humanised anti-PD-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and blocks its interaction with the ligands PD-L1 and PD-L2.[3]

In addition to GARNET, dostarlimab is being investigated for women with recurrent or primary advanced endometrial cancer in combination with standard of care (chemotherapy) in the phase III RUBY trial.[4] Dostarlimab is also being evaluated in combination with other therapeutic agents for patients with advanced solid tumours or metastatic cancer.

About endometrial cancer[v]
Endometrial cancer is a main type of uterine cancer that forms in the inner lining of the uterus, known as the endometrium. Endometrial cancer can be classified as mismatch repair-deficient/microsatellite instability-high or mismatch repair-proficient/microsatellite stable. There are limited treatment options for women whose disease progresses on or after first-line therapy. Endometrial cancer is the sixth most common cancer in women worldwide.[6]

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.

ACCENT THERAPEUTICS ANNOUNCES $63 MILLION SERIES B FINANCING TO ADVANCE NOVEL, PRECISION CANCER THERAPIES TARGETING RNA-MODIFYING PROTEINS

On April 23, 2020 Accent Therapeutics, a biopharmaceutical company developing breakthrough treatments for cancer patients, reported that it has completed a $63 million Series B financing (Press release, Accent Therapeutics, APR 23, 2020, View Source [SID1234556529]). The Series B was led by EcoR1 Capital with participation by GV, AbbVie Ventures, The Mark Foundation for Cancer Research, NS Investment and Droia Ventures as well as existing investors, Atlas Venture and The Column Group.

Proceeds from the financing will be used to advance the development of Accent’s novel therapies targeting RNA-modifying proteins (RMPs), including its lead programs METTL3 and ADAR1, and to continue to expand its pipeline in the rich target space of RNA modification.

"We are thrilled to have the support of this remarkable group of investors that share our vision for developing novel therapies for patients in need," said Shakti Narayan, Chief Executive Officer of Accent Therapeutics. "With the progress we have made to-date and expect to make in the coming months, the next phase of Accent’s growth is set to be truly transformational."

Since launching in 2018, Accent has advanced a broad pipeline of programs, including its two lead programs – METTL3 and ADAR1. METTL3 is an RNA methyltransferase implicated in AML, specific solid tumors and immuno-oncology. ADAR1 is an RNA editor with compelling validation for solid tumors with elevated intrinsic Type I interferon-stimulated gene signaling (comprising ~15-30% of solid tumors) and has also been suggested to play a key role in immuno-oncology. By targeting the proteins that modify RNA, Accent is able to apply the proven approach of enzyme-directed small molecule therapies to a rich and novel class of enzymes with the ability to impact RNA pathobiology.

"Opportunities to have such a broad impact in novel areas of biology are becoming increasingly rare," said Oleg Nodelman, Founder and Managing Director of EcoR1 Capital. "The team at Accent is well-positioned to lead this area of drug development and achieve the rich therapeutic potential of these exciting programs."

Dynavax to Report First Quarter 2020 Financial Results and Host Conference Call on May 7, 2020

On April 23, 2020 Dynavax Technologies Corporation (Nasdaq: DVAX), a biopharmaceutical company focused on developing and commercializing novel vaccines, reported that it will report first quarter 2020 financial results on Thursday, May 7, 2020, after the U.S. financial markets close (Press release, Dynavax Technologies, APR 23, 2020, View Source [SID1234556528]).

Dynavax will host a conference call and live audio webcast on Thursday, May 7, 2020 at 4:30 p.m. (ET)/1:30 p.m. (PT).

The live audio webcast may be accessed through the "Events & Presentations" page on the "Investors" section of the Company’s website at www.dynavax.com. Alternatively, participants may dial (866) 420-4066 (domestic) or (409) 217-8237 (international) and refer to conference ID 1178679. A replay of the webcast will be available for 30 days following the live event.

CStone Pharmaceuticals has submitted the application for listing of new drugs in mainland China for the first time! The State Drug Administration accepts applications for two indications for the first-in-class precision targeting drug avapritinib for gastrointestinal stromal tumors

On April 23, 2020 CStone Pharmaceuticals reported that the China National Medical Products Administration (NMPA) has accepted the New Drug Application (NDA) of the precision therapy avapritinib for two indications, one for the treatment of adults with unresectable or metastatic GIST harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations; the other for the treatment of adults with unresectable or metastatic fourth-line GIST (Press release, CStone Pharmaceauticals, APR 23, 2020, View Source [SID1234556527]). Developed by CStone’s partner Blueprint Medicines, avapritinib is an investigational, orally available, potent and selective inhibitor of KIT and PDGFRA mutant kinases. This is the first time CStone has submitted an NDA to the NMPA and marks another milestone in the Company’s transition toward commercialization.

With an annual incidence rate of 1-1.5 per 100,000, there are approximately 14,000 to 21,000 new cases of GIST in China every year1, and around 90% of these cases are associated with dysregulated cell growth due to mutations in KIT or PDGFRA tyrosine kinases. In January 2020, avapritinib was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations, and became the first precision medicine approved for the treatment of GIST harboring a PDGFRA exon 18 mutation in the United States.

"In just three months after avapritinib was approved by the U.S. FDA, CStone has submitted NDAs for this drug candidate in Taiwan and mainland China, which we hope will soon make this first-in-class precision therapy candidate accessible to patients with advanced GIST in Greater China," said Dr. Frank Jiang, Chairman and CEO of CStone. "As CStone continues to accelerate its transition toward commercialization, we plan to submit several NDAs in China across multiple indications for our lead assets in the next few months."

"Avapritinib has demonstrated outstanding antitumor activity and a well-tolerated safety profile in advanced PDGFRA exon 18 mutant GIST and fourth-line GIST. Due to the very limited benefits from approved treatment options in these two groups of GIST patients, there is an urgent unmet clinical need for new therapies," said Lin Shen, M.D., Professor and Director of Department of Gastrointestinal Oncology, Vice President of Peking University Cancer Hospital and Institute, and the principal investigator for the bridging study of avapritinib in GIST in China. "As a physician, I hope avapritinib will soon be available in our clinical practice for the treatment of advanced GIST."

Results from the Phase I NAVIGATOR study of avapritinib in PDGFRA exon 18 mutant GIST and fourth-line GIST were presented at the Connective Tissue Oncology Society Annual Meeting in November 2019. As of the data cutoff date of November 16, 2018:

43 patients with PDGFRA exon 18 mutant GIST and 111 patients with fourth-line GIST were treated at a starting dose of 300 or 400 mg once daily and evaluable for response assessments.
In patients with PDGFRA Exon 18 mutant GIST, the overall response rate (ORR) was 86% with one response pending confirmation, and the median duration of response (DOR) was not reached.
In patients with fourth-line GIST, the ORR was 22% with one response pending confirmation, and the median DOR was 10.2 months.

The Phase I/II bridging study conducted by CStone in patients with advanced GIST in China has produced encouraging preliminary results demonstrating avapritinib was well-tolerated, and safety and pharmacokinetic profiles were consistent with those previously reported for the global NAVIGATOR study.

"The current treatment approach for GIST in China is mainly based on sequential tyrosine kinase inhibitors (TKIs), but the approved TKIs only offer limited efficacy2 in patients with PDGFRA D842V mutations. Moreover, Chinese patients with fourth-line GIST face challenges on multiple fronts, including drug-resistant mutations and a lack of effective treatment options," said Dr. Jason Yang, Chief Medical Officer of CStone. "I am pleased that the bridging study in China has yielded results consistent with those from the global NAVIGATOR study, and I hope patients with advanced GIST who are in urgent need for new treatment options will benefit from this precision therapy in the near future."

CStone Pharmaceuticals and Blueprint Medicines have an exclusive collaboration and license agreement for the development and commercialization of avapritinib and certain other drug candidates in mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for these licensed products in the rest of the world.

AIVITA Biomedical Publishes Study Comparing Immune Responses and Associated Survivals Induced by Dendritic and Tumor Cell Vaccines

On April 23, 2020 AIVITA Biomedical, Inc., a biotechnology company specializing in innovative cell therapy applications, reported the publication of a paper titled, "Cytokine network analysis of immune responses before and after autologous dendritic cell and tumor cell vaccine immunotherapies in a randomized trial," in the Journal of Translational Medicine (Press release, AIVITA Biomedical, APR 23, 2020, View Source [SID1234556526]). Robert O. Dillman, M.D., chief medical officer at AIVITA, and Gabriel I Nistor, M.D., chief scientific officer at AIVITA, authored the article.

The publication provides insight into the innate and adaptive immune responses induced by patient-specific autologous dendritic cell vaccines (DCV) and autologous tumor cell vaccines (TCV), and their impact on survival. DCV was associated with a multipronged innate and adaptive immune response and correlated with improved survival compared to TCV.

In a randomized Phase 2 trial conducted in patients with melanoma, blood samples were obtained at one week before and one week after a course of three weekly injections, which either included dendritic cells loaded ex vivo with antigens from autologous irradiated tumor-initiating cells (DCV), or autologous irradiated tumor-initiating cells alone (TCV). Cytokine network analysis techniques used to analyze the serologic immune responses generated by each immunotherapy confirmed they triggered differing responses. The results help provide insight into a potential underlying immunologic mechanism of action that contributes to improved survival in DCV-treated patients.

"This analysis reinforces conclusions from our patient-specific cancer vaccine survival data, which suggested that ex-vivo processing of the same tumor antigens by autologous dendritic cells induces a more advantageous immune response than antigen-only based tumor cell vaccines," said Dr. Nistor. "This is reassuring as we continue to further optimize our unique approach in which we use enhanced autologous dendritic cells for targeting each patient’s own tumor."

AIVITA is currently conducting three independent clinical studies investigating its platform immunotherapy in patients with ovarian cancer, glioblastoma and melanoma. AIVITA uses 100% of proceeds from the sale of its ROOT of SKIN skincare line to support the development of its cancer therapeutic pipeline.

About AIVITA’S Clinical Trials

OVARIAN CANCER

AIVITA’s ovarian Phase 2 double-blind study is active and enrolling approximately 99 patients who are being randomized in a 2:1 ratio to receive either the autologous tumor-initiating cell-targeting immunotherapy or autologous monocytes as a comparator.

Patients eligible for randomization and treatment will be those (1) who have undergone debulking surgery, (2) for whom a cell line has been established, (3) who have undergone leukapheresis from which sufficient monocytes were obtained, (4) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), and (5) who have completed primary therapy. The trial is not open to patients with recurrent ovarian cancer.

For additional information about AIVITA’s AVOVA-1 trial patients can visit: www.clinicaltrials.gov/ct2/show/NCT02033616

GLIOBLASTOMA

AIVITA’s glioblastoma Phase 2 single-arm study is active and is enrolling approximately 55 patients to receive the tumor-initiating cell-targeting immunotherapy.

Patients eligible for treatment will be those (1) who have recovered from surgery such that they are about to begin concurrent chemotherapy and radiation therapy (CT/RT), (2) for whom an autologous tumor cell line has been established, (3) have a Karnofsky Performance Status of > 70 and (4) have undergone successful leukapheresis from which peripheral blood mononuclear cells (PBMC) were obtained that can be used to generate dendritic cells (DC). The trial is not open to patients with recurrent glioblastoma.

For additional information about AIVITA’s AV-GBM-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03400917

MELANOMA

AIVITA’s melanoma Phase 1B open-label, single-arm study will establish the safety of administering anti-PD1 monoclonal antibodies in combination with AIVITA’s tumor-initiating cell-targeting immunotherapy in patients with measurable metastatic melanoma. The study will also track efficacy of the treatment for the estimated 14 to 20 patients. This trial is not yet open for enrollment.

Patients eligible for treatment will be those (1) for whom a cell line has been established, (2) who have undergone leukapheresis from which sufficient monocytes were obtained, (3) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), (4) who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations and (5) are about to initiate anti-PD1 monotherapy.

For additional information about AIVITA’s AV-MEL-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03743298