On October 19, 2023 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted its New Drug Application (NDA) for XTANDI (enzalutamide) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) (Press release, Astellas, OCT 19, 2023, View Source [SID1234636205]).

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Ahsan Arozullah, M.D., MPH, Senior Vice President and Head of Oncology Development, Astellas
"With a median survival of only three to four years from starting androgen deprivation therapy, patients with metastatic hormone-sensitive prostate cancer in China are in need of new treatment options. We look forward to working with the CDE to advance this NDA, which represents the third application acceptance for XTANDI in advanced prostate cancer in China."

The NDA is based on results from the Phase 3 China ARCHES study. In the study, 180 Chinese patients with mHSPC in mainland China were randomized to receive XTANDI plus androgen deprivation therapy (ADT) or placebo plus ADT. The study met its primary endpoint, demonstrating a statistically significant improvement in time to prostate-specific antigen (PSA) progression (TTPP), defined as a ≥ 25% increase and an absolute increase of ≥ 2 µg/L (2 ng/mL) above the nadir (i.e., lowest PSA value observed post baseline or at baseline), which is confirmed by a second consecutive value at least 3 weeks later. These topline findings also showed consistent results with those in Astellas’ global Phase 3 ARCHES study in the same target population.7

In China ARCHES, the safety of XTANDI plus ADT was broadly consistent with the known safety profile for the medication.

Results from China ARCHES will be presented in a poster presentation during the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023.

XTANDI has not been approved by the NMPA for the treatment of mHSPC.

Astellas has already reflected the impact from this acceptance in its financial forecast of the current fiscal year ending March 31, 2024.

About Metastatic Hormone-Sensitive Prostate Cancer
In China, prostate cancer is the most common tumor in male genitourinary cancers.1 It is the second most common cancer in men worldwide.2 Prostate cancer is considered metastatic once it has spread outside of the prostate gland to other parts of the body, such as distant lymph nodes, bones, lungs, and liver.3 Men are considered hormone- (or castration-) sensitive if their disease still responds to medical or surgical treatment to lower testosterone levels.4 Metastatic hormone-sensitive prostate cancer (mHSPC) has a median survival of approximately 3-4 years for men starting treatment with ADT.5

About the China ARCHES Trial
The company-sponsored, multicenter, Phase 3, randomized, double-blind, placebo-controlled China ARCHES trial (NCT04076059) enrolled 180 Chinese patients with metastatic hormone-sensitive prostate cancer (mHSPC) across 30 sites in mainland China. Patients in the trial were randomized to receive XTANDI 160 mg daily or placebo and continued on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or had a history of bilateral orchiectomy. The primary endpoint of the trial was time to prostate-specific antigen (PSA) progression (TTPP), defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir, which is confirmed by a second consecutive value at least 3 weeks later. Secondary endpoints include radiographic progression-free survival (rPFS), time to first Symptomatic Skeletal Event (SSE), time to castration resistance, PSA response (≥ 50%), PSA response (≥ 90%), time to initiation of new antineoplastic therapy, PSA undetectable rate, which is defined as the percentage of subjects with detectable (≥ 0.2 ng/mL) PSA at baseline, which becomes undetectable (< 0.2 ng/mL) during study treatment, and objective response rate (ORR).

For more information on the China ARCHES trial, go to www.clinicaltrials.gov.

About XTANDI (enzalutamide soft capsules)
Enzalutamide is an androgen receptor signaling inhibitor indicated for the treatment of adult men with non-metastatic castration-resistant prostate cancer (nmCRPC) with high-risk of metastasis or metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated.6

Important Safety Information
For Important Safety Information for enzalutamide please see the Package Insert.

On October 19, 2023 Mayo Clinic and Oxford Nanopore Technologies, the company delivering a new generation of nanopore-based molecular sensing technology, reported a multi-year joint development collaboration to develop new clinical tests for diseases and improve patient care (Press release, Mayo Clinic, OCT 19, 2023, View Source [SID1234636165]).

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Mayo Clinic and Oxford Nanopore have identified several areas of development, spanning a wide breadth of applications from translational research in human genetics to detection of genetic predisposition to cancer.

"We are proud to work with Mayo Clinic to support the development of new tests that will assist clinical decision-making and improve patient lives. This collaboration shows that Oxford Nanopore’s technology is ready to support development and validation of assays for clinical care, and it underscores our maturity and long-term vision to transform this space. We have long held the ambition to become a utility player in world-renowned, global clinical centers of excellence, and this is our first step toward achieving that vision," says Gordon Sanghera, CEO, Oxford Nanopore Technologies.

Nanopore sequencing is well positioned to serve Mayo Clinic’s goals of improving testing in some of the hardest-to-characterize conditions. The ability to sequence any-length fragments of DNA — from short to long and ultra-long — and examine methylation in real time offers the potential to provide clinicians with a more complete picture of an evolving cancer genome quickly and accurately. Methylation is particularly important, as this typically requires bisulfite conversions and additional cost yet is key to unmasking crucial insights.

"Pairing Oxford Nanopore’s innovative nanopore sequencing with Mayo Clinic’s world-class clinical and diagnostic testing knowledge further helps advance patient care," says Bobbi Pritt, M.D., interim chair of Mayo Clinic’s Department of Laboratory Medicine and Pathology. "We are excited to collaborate with Oxford Nanopore on this effort to develop new clinical tests that will provide the right answers for patients at the right time."

The collaboration activities will take place on Mayo Clinic’s campus in Rochester, Minnesota.

On October 19, 2023 Foundation Medicine, Inc., reported that the company will present 11 abstracts demonstrating the value of high-quality biomarker tests to inform cancer care at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting from October 20-24 in Madrid, Spain (Press release, Foundation Medicine, OCT 19, 2023, View Source [SID1234636164]).

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Late Breaking Results from the CUPISCO Study

In a late-breaking abstract, Foundation Medicine and Roche share results from the randomized precision oncology study, CUPISCO, designed to prospectively assess the efficacy of molecularly guided therapy for patients with unfavorable subset cancer of unknown primary (CUP). In patients with CUP, the tumor of origin is unknown, which has historically made targeted treatment challenging. As a result, there has been little progress in improving the poor outcomes for these patients. The study demonstrates how genomic profiling using Foundation Medicine’s FDA-approved FoundationOneCDx and FoundationOneLiquid CDx diagnostic tests positively impacted progression-free survival and overall survival in patients with CUP.

Primary analysis of efficacy and safety in CUPISCO: A randomised, global study of targeted therapy or cancer immunotherapy guided by genomic profiling vs platinum-based chemotherapy (CTX) in patients (pts) with treatment-naive, unfavourable carcinoma-of-unknown-primary-origin (CUP) (Proffered Paper Session 1, LBA16)
Highlighting Expanded Capabilities of ctDNA Tumor Fraction

Research continues to validate the power of circulating tumor DNA (ctDNA) tumor fraction, which is a measurement of the level of ctDNA within a liquid biopsy sample, to support the interpretation of liquid biopsy test results. Two new studies being presented by Foundation Medicine and its collaborators at ESMO (Free ESMO Whitepaper) highlight the differentiated ctDNA tumor fraction reporting capabilities of the company’s FoundationOneLiquid CDx test. The research explores ctDNA tumor fraction’s correlation with metabolic tumor volume on with a PET scan, and its prognostic use in bladder cancer, respectively.

Clinical and genomic correlates of plasma circulating tumor DNA (ctDNA) tumor fraction (TF) in patients with advanced NSCLC (Presentation Number 2339P)
Relationship of Tumor Fraction in Circulating Tumor DNA (ctDNA) with Prognosis in Patients with Advanced Urothelial Cancer (Presentation Number 2396P)
Demonstrating Differences in Genetic Ancestry in Biliary Tract Cancer

Molecular differences between genetic ancestries in patients with biliary tract cancer (BTC) and the impact of those differences on prognosis and treatment response are largely unknown. In a study conducted with The University of Texas MD Anderson Cancer Center, researchers looked at over 10,000 cases of BTC in patients of African and European descent and identified key clinical and genomic differences.

Molecular Profiling of Biliary Tract Cancer (BTCs) in Patients of African and European ancestries​ (Presentation Number 113P)
"The research we are presenting at this year’s ESMO (Free ESMO Whitepaper) reinforces the ever-expanding clinical utility across disease types of our high-quality tissue and blood-based tests," says Mia Levy, MD, PhD, chief medical officer at Foundation Medicine. "Alongside our collaborators, we’re proud to share our continued progress in bringing more knowledge and cancer treatment options to the cancer community."

The following is a list of abstracts that will be presented at the meeting. To access all abstracts being presented at ESMO (Free ESMO Whitepaper), please visit ESMO (Free ESMO Whitepaper).org.

Follow Foundation Medicine on Twitter and LinkedIn for more updates from #ESMO23 and visit us in person at Booths 727 and 728.

Abstract #

Title

Collaborators

Product

Proffered Paper (Oral)

LBA16

Saturday, October 21

10:35-10:45 a.m.

Primary analysis of efficacy and safety in CUPISCO: A randomised, global study of targeted therapy or cancer immunotherapy guided by genomic profiling vs platinum-based chemotherapy (CTX) in patients (pts) with treatment-naive, unfavourable carcinoma-of-unknown-primary-origin (CUP)

Oncologists from Europe, Asia and Oceania, Central lab at University Hospital of Zurich

FoundationOneCDx

FoundationOneLiquid CDx

1182O

Sunday, October 22

9:20-9:30 a.m.

Temozolomide treatment induces an MMR-dependent hypermutator phenotype in well differentiated pancreatic neuroendocrine tumors

Hôpital Saint-Louis AP-HP

FoundationOneCDx

Posters

2352P

Sunday, October 22

Sex-Based Difference in Gene Alterations and Biomarkers in Anal Squamous Cell Carcinoma

IRCCS San Raffaele Scientific Institute

FoundationOneCDx

771P

Sunday, October 22

Genomic Characterization of Advanced Endometrial Carcinosarcoma: Identification of Potentially Actionable Targets

IRCCS Istituto Romagnolo per lo Studio dei Tumori, IRCCS San Raffaele Scientific Institute, IRCCS Istituto Nazionale Tumori

FoundationOneCDx

2339P

Sunday, October 22

Clinical and genomic correlates of plasma circulating tumor DNA (ctDNA) tumor fraction (TF) in patients with advanced NSCLC

Institut Gustave Roussy

FoundationOneLiquid CDx

113P

Monday, October 23

Molecular Profiling of Biliary Tract Cancer (BTCs) in Patients of African and European ancestries

MD Anderson

FoundationOneCDx

738P

Monday, October 23

Penile squamous cell carcinoma with high and very high tumor mutational burden: A genomic landscape and real-world clinical outcome study

Upstate Medical University, University of Washington, Moffit Cancer Center,

MD Anderson Cancer Center, San Rafael University

FoundationOneCDx

2396P

Monday, October 23

Relationship of Tumor Fraction in Circulating Tumor DNA (ctDNA) with Prognosis in Patients with Advanced Urothelial Cancer

Fox Chase Cancer Center, Temple University

FoundationOneLiquid CDx

1946P

Monday, October 23

Primary Sarcomas of the Urinary Bladder (BSar): A Genomic Landscape and Clinical Outcome Study

Upstate Medical University, University of Washington, Moffit Cancer Center, MD Anderson Cancer Center, San Rafael University

FoundationOneCDx

2395P

Monday, October 23

Micropapillary Histology (MPUC) and Extra-cellular Domain ERBB2 (ERBB2 ECD+) Mutations in Urothelial Bladder Cancer (UBC)

Upstate Medical University, University of Washington, Moffit Cancer Center, MD Anderson Cancer Center, San Rafael University

FoundationOneCDx

2400P

Monday, October 23

Frequency and Nature of Genomic Alterations (GA) in ERBB2-altered Urothelial Bladder Cancer (UBC)

Upstate Medical University, University of Washington, Moffit Cancer Center, MD Anderson Cancer Center, San Rafael University

On October 19, 2023 Personalis, Inc. (Nasdaq: PSNL), a leader in precision oncology, reported that a late-breaking abstract featuring data for the company’s NeXT Personal whole genome-based, tumor-informed assay for ultra-sensitive ctDNA detection, has been accepted and selected for a proffered paper presentation at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, on October 21 in Madrid, Spain (Press release, Personalis, OCT 19, 2023, View Source [SID1234636163]).

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Presentation #LBA55

Title: "An ultra-sensitive and specific ctDNA assay provides novel pre-operative disease stratification in early stage lung cancer"
Location: Salamanca Auditorium – Hall 3
Date: October 21, 2023
Time: 10:15 – 10:25 CEST
Presenter: Dr. James R. Black MD, PhD, Francis Crick Institute

Late-breaking abstracts are typically reserved for high-quality, new research findings from randomized phase II or phase III trials with implications for clinical practice or understanding of disease processes. Proffered papers are oral presentations of original data of superior quality, followed by expert discussion and perspectives.

On October 19, 2023 Scholar Rock (NASDAQ: SRRK), a Phase 3 clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported that it will present data from DRAGON, a Phase 1 study of SRK-181 in patients with advanced solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting in San Diego on November 1-5 (Press release, Scholar Rock, OCT 19, 2023, View Source [SID1234636162]). In one poster presentation, Scholar Rock will share preliminary biomarker data from Part B of the trial, and in a second poster presentation, provide safety, efficacy, and biomarker results of SRK-181 in anti-PD-1 resistant metastatic clear cell renal cell carcinoma (ccRCC) patients from both Parts A and B.

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"We are excited to present clinical and biomarker updates on the DRAGON study, which build upon the safety and efficacy data to date in the ccRCC cohort of the trial and support our goal of establishing the proof of mechanism of SRK-181," said Jay Backstrom, M.D., MPH, President and Chief Executive Officer of Scholar Rock. "As a selective latent TGFβ1 inhibitor, SRK-181 has the potential to transform cancer immunotherapy by helping to overcome resistance to checkpoint inhibitor therapy. This investigational medicine demonstrates the promise of Scholar Rock’s unique discovery platform."

Details of the presentations are as follows:

Title: Establishing Proof of Mechanism in Patients: Preliminary Biomarker Data of SRK-181 (a latent TGFβ1 inhibitor) from DRAGON Study
Presentation Type: Poster 726
Presenter: Susan Henry, PhD, Senior Director, Translational Sciences, Scholar Rock, Inc.
Location: Exhibit Halls A and B1, San Diego Convention Center
Date/Time: November 4, 11:55 AM – 1:25 PM PDT and 7 – 8:30 PM PDT

Title: Safety, efficacy, and biomarker results of SRK-181, a latent TGFβ1 inhibitor, in anti-PD-1 resistant metastatic ccRCC patients
Presentation Type: Poster 666
Presenter: Timothy Yap, MBBS, PhD, FRCP, Medical Oncologist and Physician-Scientist; and Associate Professor, Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center
Location: Exhibit Halls A and B1, San Diego Convention Center
Date/Time: November 4, 11:55 AM – 1:25 PM PDT and 7 – 8:30 PM PDT

The abstracts for these presentations will be available on SITC (Free SITC Whitepaper)’s website on Oct 31, 2023: View Source

The presentations will be made available in the Publications & Posters section of Scholar Rock’s website following the conference.

For conference information, visit View Source

About SRK-181

SRK-181 is a selective inhibitor of TGFβ1 activation being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies, in advanced cancer. TGFβ1 is the predominant TGFβ isoform expressed in many human tumor types. Based on analyses of various human tumors that are resistant to anti-PD-(L)1 therapy, data suggest that TGFβ1 is a key contributor to the immunosuppressive tumor microenvironment, excluding and preventing entry of cytotoxic T cells into the tumor, thereby inhibiting anti-tumor immunity. (1) SRK-181 specifically targets the latent TGFβ1 isoform in a context-independent manner, designed to enable complete inhibition of TGFβ1 in all compartments within the tumor microenvironment. Scholar Rock believes that SRK-181 has the potential to overcome this immune cell exclusion and induce tumor regression when administered in combination with anti-PD-(L)1 therapy while potentially avoiding toxicities associated with non-selective TGFβ inhibition. The DRAGON Phase 1 proof-of-concept clinical trial (NCT04291079) in patients with locally advanced or metastatic solid tumors is ongoing. The trial is currently enrolling and dosing patients in multiple proof of concept cohorts conducted in parallel, including urothelial carcinoma (UC), cutaneous melanoma (MEL), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and clear cell renal cell carcinoma (ccRCC). SRK-181 is an investigational product candidate and its efficacy and safety have not been established. SRK-181 has not been approved for any use by the FDA or any other regulatory agency.