On June 3, 2019 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has launched FoundationOne CDx Cancer Genomic Profile, (hereafter "the Program") a next-generation sequencing based gene mutation analysis program (Press release, Chugai, JUN 3, 2019, View Source [SID1234536853]). Also, SRL Inc. has started providing testing services for the Program today.

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FoundationOne CDx is the first cancer genomic test in Japan which obtained regulatory approval for the two functions of gene mutation analysis program (for use in cancer genome profiling) for solid tumors, and somatic gene mutation analysis program (for use in assessing anticancer drug indications). The approval was granted by the Ministry of Health, Labour and Welfare on December 27, 2018.

"FoundationOne CDx Cancer Genomic Profile will open up a new horizon for personalized cancer care. I am delighted that the program is now available for patients and healthcare providers in Japan," said Tatsuro Kosaka, Chugai’s President and CEO. "Through this program, Chugai will further strive to realize advanced and sustainable patient-centric healthcare by promoting access to treatments optimized to each patient."

Developed by Foundation Medicine Inc., FoundationOne CDx Cancer Genomic Profile is a next-generation sequencing based in vitro diagnostic device for the detection and analysis of substitutions, insertion and deletion alterations, and copy number alterations in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from patient’s tumor tissues. As a comprehensive companion diagnostic function, it can be also used as a companion diagnostic for certain molecular-targeted drugs approved in Japan.

As a leading company in the field of oncology, Chugai is committed to realize advanced personalized oncology care and contribute to patients and healthcare providers through comprehensive genomic profiling.

[Notes]
A press release issued on March 19, 2019: Miraca and Chugai Enter into Business Partnership Agreement for "FoundationOne CDx Cancer Genome Profile"
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Approval information

Brand name FoundationOne CDx Cancer Genomic Profile
Nonproprietary name
Gene mutation analysis program (for use in cancer genome profiling)
Somatic gene mutation analysis program (for use in assessing anticancer drug indications)
Approval date December 27, 2018
Intended uses or indications
The Product is used for comprehensive genomic profiling of tumor tissues in patients with solid cancers.
The Product is used for detecting gene mutations and other alterations to support the assessment of drug indications listed in the table below.
Alterations Cancer type Relevant drugs
EGFR exon 19 deletions and EGFR exon 21 L858R alterations Non-small cell lung cancer (NSCLC) afatinib dimaleate, erlotinib hydrochloride, gefitinib, osimertinib mesylate
EGFR exon 20 T790M alterations osimertinib mesylate
ALK fusion genes alectinib hydrochloride, crizotinib, ceritinib
BRAF V600E and V600K alterations Malignant melanoma dabrafenib mesylate, trametinib dimethyl sulfoxide, vemurafenib
ERBB2 copy number alterations (HER2 gene amplification positive) Breast cancer trastuzumab (genetical recombination)
KRAS/NRAS wild-type Colorectal cancer cetuximab (genetical recombination), panitumumab (genetical recombination)
Conditions for approval
The necessary measures must be taken to ensure that the product is used by a physician with adequate knowledge and experience of cancer genomic medicine at a medical institution with a cancer genome profiling-based medical system pursuant to the "Guidelines for the Development of Core Hospitals and Other Facilities for Cancer Genomic Medicine," and in compliance with the scope and timing of testing stipulated in the most recent guidelines, etc., of relevant academic societies.
Appropriate procedures and controls to protect personal information and up-to-date security and privacy protection measures to prevent unauthorized access must be implemented for tumor tissue specimens sent to the laboratory and for information obtained from these specimens.
Quality control of input data must be performed as described in the Remarks column of the attached Application Form. Any changes to the quality control of input data as described in the Remarks column of the Application Form (excluding minor changes specified by Order of the MHLW in Article 23-2-5, paragraph (11) of the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices ["the Act"]) must be approved by the MHLW Minister pursuant to Article 23-2-5, paragraph (11) of the Act. Note that this approval applies mutatis mutandis to the provisions of Article 23-2-5 paragraph (13), Article 23-2-6, and Article 23-2-7 of the Act.

On June 3, 2019 Iovance Biotherapeutics, Inc presented the corporate presentation (Presentation, Iovance Biotherapeutics, JUN 3, 2019, View Source [SID1234536851]).

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On June 3, 2019 Dynavax Technologies Corporation (NASDAQ: DVAX), reported that Ryan Spencer, Senior Vice President, Commercial, and Interim Co-President, will present at the William Blair & Co. Annual Growth Stock Conference on Thursday, June 6, at 9:20 a.m. C.T (Press release, Dynavax Technologies, JUN 3, 2019, View Source [SID1234536850]).

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The presentation will be webcast and may be accessed at the "Events & Presentations" section of the Company’s website at View Source

On June 3, 2019 AIVITA Biomedical, Inc., a biotech company specializing in innovative stem cell applications, reported that Chief Medical Officer Dr. Robert O. Dillman presented clinical data on melanoma patients treated with patient-specific vaccines on June 1 at the 55th Annual Meeting of ASCO (Free ASCO Whitepaper) in Chicago, Illinois (Press release, AIVITA Biomedical, JUN 3, 2019, View Source [SID1234536849]). The data is being published concurrently in the journal Melanoma Management.

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The abstract and publication describe survival data for 72 patients pooled from two Phase 2 trials. In the first trial conducted in 54 patients, the projected median overall survival was 54% at a time when median follow up was 4.5 years (Dillman et al. Cancer Biother Radiopahrm 2009;24:311-319.). Actual 5-year survival was 50% once all patients had been followed a minimum of five years. In the second Phase 2 trial patients were randomized for treatment with either their patient-specific dendritic cell vaccine (DCV) or patient-specific tumor cell vaccine (TCV). In both treatment arms the source of antigen was autologous tumor cells that were self-renewing in cell culture. Median overall survival was better in the DCV-treated patients: median survival 40.3 vs 20.5 months, 3-year actual survival of 61% vs 25% (p=0.018), and a 70% reduction in the risk of death (p=0.0053) [Dillman et al. J Immunother Cancer 2018;6:19.] The data for DCV-treated patients was pooled in order to address questions related to survival of specific subsets of patients [Dillman et al. Melanoma Manag 2019]. All patients had been followed for five years. The data showed that for melanoma patients who had recurrent Stage III disease that was not measurable at the time DCV-treatment was initiated, the 5-year survival rate was 72%. In melanoma patients who had previous Stage IV melanoma but did not have measurable disease at the time of treatment, the 5-year survival rate was 53%. Patients with measurable Stage IV melanoma had a median survival of 18.5 months with a two-year survival rate of 46%, which compares favorably to results achieved with anti-PD-1 checkpoint inhibitors in similar patients.

AIVITA is currently conducting three clinical studies investigating its platform ROOT OF CANCER therapy 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 treatment of women with ovarian cancer.

About ROOT OF CANCER

AIVITA’s treatment is a platform technology applicable to most solid tumor types and consists of autologous dendritic cells loaded with autologous tumor antigens from purified autologous self-renewing tumor-initiating cells.

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 cancer stem 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 cancer stem 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 the cancer stem 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

On June 3, 2019 Bayer reported results of a new analysis from clinical trials investigating Vitrakvi (larotrectinib) in patients with TRK fusion cancer with primary central nervous system (CNS) tumors or brain metastases (Press release, Bayer, JUN 3, 2019, View Source [SID1234536847]). The analysis included 14 patients with primary CNS tumors evaluable for efficacy, including cases of glioma, glioblastoma, glioneural tumors, and astrocytoma. In this population, Vitrakvi demonstrated an overall response rate (ORR) of 36% (n=5; 95% CI: 13-65), including 14% complete responses (CR, n=2) and 21% partial responses (PR, n=3). The remaining 64% of patients had stable disease and no patients experienced progressive disease as best response based on investigator assessment using RANO (Response Assessment in Neuro-Oncology) and RECIST 1.1 (Response Evaluation Criteria In Solid Tumors). In five evaluable patients with NTRK gene fusion positive solid tumors with brain metastases, the ORR was 60% (n=3 PRs; 95% CI: 15-95) based on investigator assessment and RECIST 1.1. The remaining 40% of patients (n=2) had stable disease.1

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Vitrakvi is indicated for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation, are either metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.2

The analysis included 24 TRK fusion cancer patients with brain metastases or primary CNS tumors who were identified from across three different clinical studies.1 Eighteen patients presented with primary CNS tumors (data cut-off February 19, 2019), of which 14 were evaluable, and six patients had non-primary CNS tumors and brain metastases, of which five were evaluable (data cut-off July 30, 2018).1 The adverse events seen in the presentations were mostly grade 1-2.3,4,5

These data were presented in an oral presentation at ASCO (Free ASCO Whitepaper) on June 3, 2019 (Abstract 2006, Session: Central Nervous System Tumors; Monday, June 3, 3:15PM – 3:27PM CDT, Room: S102).

"These data are important as we continue to see efficacy with Vitrakvi in TRK fusion cancer across different tumor types and ages," said Scott Z. Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer’s Pharmaceuticals Division. "The responses in these patients underscore the importance of widespread genomic cancer testing to identify patients who may be appropriate for this treatment."

Data on Vitrakvi in CNS tumors

A total of 24 patients with intracranial disease were identified from three clinical studies (adult Phase I trial, NCT02122913, 1 patient; Pediatric Phase I/II trial SCOUT, NCT02637687, 12 patients; and the adult/adolescent Phase II basket trial NAVIGATE, NCT02576431, 11 patients).1

About Vitrakvi (larotrectinib)
Vitrakvi is indicated for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation, are either metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.2 This indication is approved under accelerated approval based on overall response rate and duration of response.2 Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.2

Important Safety Information for VITRAKVI (larotrectinib)

Neurotoxicity: Among the 176 patients who received VITRAKVI, neurologic adverse reactions of any grade occurred in 53% of patients, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and 0.6% of patients, respectively. The majority (65%) of neurologic adverse reactions occurred within the first three months of treatment (range 1 day to 2.2 years). Grade 3 neurologic adverse reactions included delirium (2%), dysarthria (1%), dizziness (1%), gait disturbance (1%), and paresthesia (1%). Grade 4 encephalopathy (0.6%) occurred in a single patient. Neurologic adverse reactions leading to dose modification included dizziness (3%), gait disturbance (1%), delirium (1%), memory impairment (1%), and tremor (1%).2

Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dose when resumed.2

Hepatotoxicity: Among the 176 patients who received VITRAKVI, increased transaminases of any grade occurred in 45%, including Grade 3 increased AST or ALT in 6% of patients. One patient (0.6%) experienced Grade 4 increased ALT. The median time to onset of increased AST was 2 months (range: 1 month to 2.6 years). The median time to onset of increased ALT was 2 months (range: 1 month to 1.1 years). Increased AST and ALT leading to dose modifications occurred in 4% and 6% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 2% of patients.2

Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.2

Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily.2

Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.2

Most Common Adverse Reactions (≥20%): The most common adverse reactions (≥20%) were: increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea (29%), dizziness (28%), cough (26%), vomiting (26%), constipation (23%), and diarrhea (22%).2

Drug Interactions: Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.2

Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.2

Please see the full Prescribing Information for VITRAKVI (larotrectinib).

About TRK Fusion Cancer
TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing an altered TRK protein.2 The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade.2 These TRK fusion proteins can act as an oncogenic driver, promoting cell proliferation and survival in tumor cell lines, leading to TRK fusion cancer, regardless of where it originates in the body.2 TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body.6 TRK fusion cancer occurs in various adult and pediatric solid tumors with varying frequency, including lung, thyroid, GI cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (mammary analogue secretory carcinoma) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma).2,6

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes five marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.