On September 8, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and genetic testing, reported it will present new data on its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress taking place Sept. 13-16 in Barcelona, Spain (Press release, Natera, SEP 8, 2024, View Source [SID1234646417]).

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!

Natera and its collaborators will present a total of nine abstracts, including five poster presentations from the GALAXY observational arm of the CIRCULATE-Japan trial, one of the largest and most comprehensive prospective studies of MRD testing in resectable colorectal cancer (CRC).

The GALAXY data includes an updated analysis of more than 2,100 patients with stage I-IV CRC, reporting 36-month disease-free survival (DFS), and, for the first time, overall survival (OS). Key highlights include:

Signatera-positive patients had significantly shorter OS compared to those who were Signatera-negative (hazard ratio of ~10), suggesting that Signatera-negative patients had an almost 10-fold advantage in OS. This compares favorably to all known guideline recommended biomarkers that typically have hazard ratios for overall survival in the 1-4 range.
Overall survival stratified by adjuvant chemotherapy (ACT) will also be presented. This will build on prior GALAXY DFS data which has shown significant benefit of ACT in Signatera-positive patients, but lack of benefit in Signatera-negative patients. The current standard of care is based on studies showing that most CRC patients derive a small ~0-5% absolute and ~10-20% relative OS benefit from ACT. Identifying subgroups where this benefit is concentrated is critical for advancing clinical management of early-stage CRC.
"ESMO 2024 will showcase some of our most impactful data in colorectal cancer to-date," said Minetta Liu, MD, chief medical officer of oncology at Natera. "Notably, we will present an updated analysis from the GALAXY arm of CIRCULATE-Japan with the first prospective read-out of overall survival based on MRD. These findings underscore the potential for Signatera to predict long-term outcomes."

Other presentations at ESMO (Free ESMO Whitepaper) will highlight new Signatera data in breast cancer and squamous cell carcinoma of the head and neck. Below is the full list of presentations:

Presentation Highlights

Poster Presentation #553P | CRC | Sept. 16 | Presenter: Jun Nagata, MD
Association of ctDNA-based MRD detection and MRD clearance with short-term overall survival in patients with resectable colorectal cancer: Updated analysis of CIRCULATE-Japan GALAXY

Poster Presentation #558P | CRC | Sept. 16 | Presenter: Kozo Kataoka, MD, PhD
Survival benefit of adjuvant chemotherapy based on molecular residual disease detection in resected colorectal liver metastases; subgroup analysis from CIRCULATE-Japan GALAXY

Oral Presentation and Additional Presentations

Oral Presentation | CRC | Presenter: Myriam Chalabi, MD
Sept. 15, 09:10 – 09:20
Neoadjuvant immunotherapy in locally advanced MMR-deficient (dMMR) colon cancer (CC): 3-year disease-free survival (DFS) from NICHE-2

Poster Presentation #923P | SCCHN | Sept. 14 | Presenter: Natasha Honoré, MD, PhD
Tumor-informed ctDNA assay to predict recurrence in locally advanced SCCHN

Poster Presentation #555P | CRC | Sept. 16 | Presenter: Tomoya Harima, MD
Association Between Copy Number Aberration and ctDNA MRD in Colorectal Cancer: CIRCULATE-Japan GALAXY

Poster Presentation #554P | CRC | Sept. 16 | Presenter: Yoshiaki Nakamura, MD, PhD
Novel Clinical Decision Support (CDS) System Optimizing Adjuvant Chemotherapy (ACT) for Colorectal Cancer (CRC) by Integrating Deep Learning and circulating tumor DNA (ctDNA) molecular residual disease (MRD): GALAXY Histotyping

Poster Presentation #545P | CRC | Sept. 16 | Presenter: Chiara M. Loeffler, MD
HIBRID: Histology and ct-DNA based Risk-stratification with Deep Learning

Poster Presentation #338TiP | Breast Cancer | Sept. 16 | Presenter: Michail Ignatiadis, MD, PhD
EORTC-2129-BCG: Elacestrant for treating ER+/HER2- breast cancer patients with ctDNA relapse (TREAT ctDNA)

Poster Presentation #314P | Breast Cancer | Sept. 16 | Presenter: Mark Magbanua, PhD
The impact of changes in tumor mutational landscape during neoadjuvant therapy on tumor-informed ctDNA testing in breast cancer patients

About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 70 peer-reviewed papers.

On September 8, 2024 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, reported the abstract sharing clinical data from its ongoing Phase 1 clinical trial of CFT1946, a novel BiDAC degrader, in mutant BRAF V600 solid tumors, was released in conjunction with the ESMO (Free ESMO Whitepaper) Congress 2024 scheduled for September 13 – 17, 2024 in Barcelona, Spain (Press release, C4 Therapeutics, SEP 8, 2024, View Source [SID1234646401]). The full abstract, which includes results with a data cut-off of April 12, 2024, can be accessed on the ESMO (Free ESMO Whitepaper) Congress 2024 website.

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!

Data on 36 patients, with a data cut-off date of July 19, 2024, will be presented as a proffered paper in an oral presentation scheduled for Friday, September 13, 2024 at 4:10 pm CEST (10:10 am ET) at the ESMO (Free ESMO Whitepaper) Congress 2024. This oral presentation will include patient demographics, safety, pharmacokinetic, pharmacodynamic and anti-tumor activity data as measured by RECIST 1.1 criteria.

ESMO Congress 2024 Presentation
Title: Preliminary Results from a Phase 1 Study of CFT1946, a Novel BiDAC Degrader in Mutant BRAF V600 Solid Tumors
Presentation Date and Time: Friday, September 13, 2024, 4:10 pm CEST (10:10 am ET)
Final Publication Number: 612O
Session Category: Proffered paper session 1
Session Title: Developmental therapeutics
Location: Santander Auditorium – Hall 5
Presenter: Maria Vieito, M.D., MSc (Barcelona, Spain)

C4T Webcast for Analysts and Investors
C4T will host a webcast on Friday, September 13, 2024 at 12:00 pm ET. To join the webcast, please visit this link or the "Events & Presentations" page of the Investors section on the company’s website at www.c4therapeutics.com. A replay of the webcast will be archived and available following the event. Additionally, following the proffered paper session at the ESMO (Free ESMO Whitepaper) Congress 2024, C4T will share that presentation on its website under the Scientific Presentations and Publications page.

On September 8, 2024 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported a poster presentation relating to Phase 2 data of vobramitamab duocarmazine in metastatic castration-resistant prostate cancer (mCRPC) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, taking place in Barcelona, Spain from September 13-17, 2024 (Press release, MacroGenics, SEP 8, 2024, View Source [SID1234646402]).

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!

The following poster will be available on Sunday, September 15, 2024:

TAMARACK: Randomized Phase 2 trial of the B7-H3 targeting antibody drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) in metastatic castration-resistant prostate cancer (mCRPC)
Presenter / Lead Author: Johann de Bono, M.D., M.Sc., Ph.D., FRCP, FMedSci, Division of Clinical Studies, Royal Marsden Hospital Institute of Cancer Research, Sutton, UK
Presentation ID: 1654P
Session Date: Sunday, September 15, 2024
Poster Display Time: 9:00 a.m. – 5:00 p.m. CEST

The abstract submitted to ESMO (Free ESMO Whitepaper) in May 2024, now available on the ESMO (Free ESMO Whitepaper) website, was based on a data cut-off from April 12, 2024, and the poster will report data from a July 9, 2024, data cut-off. Data to be presented at ESMO (Free ESMO Whitepaper) will include updated safety and efficacy data, including the study’s primary endpoint of landmark 6-month radiographic progression-free survival (rPFS), as well as immature median rPFS that may change as additional PFS events accrue. The poster to be presented at ESMO (Free ESMO Whitepaper) will be published under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source on September 15, 2024.

Conference Call

The Company anticipates hosting a conference call to discuss the TAMARACK poster data and provide a general corporate update on Monday, September 16, 2024, at 8:00 a.m. ET. The call will be led by Scott Koenig, M.D., Ph.D., President and Chief Executive Officer; Stephen Eck, M.D., Ph.D., Senior Vice President – Clinical Development and Chief Medical Officer; and Jim Karrels, Senior Vice President – Chief Financial Officer.

To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company’s website at View Source. A recorded replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.

On September 9, 2024 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported a poster presentation relating to Phase 2 data of vobramitamab duocarmazine in metastatic castration-resistant prostate cancer (mCRPC) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, taking place in Barcelona, Spain from September 13-17, 2024 (Press release, MacroGenics, SEP 8, 2024, View Source [SID1234646437]).

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!

The following poster will be available on Sunday, September 15, 2024:

TAMARACK: Randomized Phase 2 trial of the B7-H3 targeting antibody drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) in metastatic castration-resistant prostate cancer (mCRPC)
Presenter / Lead Author: Johann de Bono, M.D., M.Sc., Ph.D., FRCP, FMedSci, Division of Clinical Studies, Royal Marsden Hospital Institute of Cancer Research, Sutton, UK
Presentation ID: 1654P
Session Date: Sunday, September 15, 2024
Poster Display Time: 9:00 a.m. – 5:00 p.m. CEST

The abstract submitted to ESMO (Free ESMO Whitepaper) in May 2024, now available on the ESMO (Free ESMO Whitepaper) website, was based on a data cut-off from April 12, 2024, and the poster will report data from a July 9, 2024, data cut-off. Data to be presented at ESMO (Free ESMO Whitepaper) will include updated safety and efficacy data, including the study’s primary endpoint of landmark 6-month radiographic progression-free survival (rPFS), as well as immature median rPFS that may change as additional PFS events accrue. The poster to be presented at ESMO (Free ESMO Whitepaper) will be published under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source on September 15, 2024.

Conference Call

The Company anticipates hosting a conference call to discuss the TAMARACK poster data and provide a general corporate update on Monday, September 16, 2024, at 8:00 a.m. ET. The call will be led by Scott Koenig, M.D., Ph.D., President and Chief Executive Officer; Stephen Eck, M.D., Ph.D., Senior Vice President – Clinical Development and Chief Medical Officer; and Jim Karrels, Senior Vice President – Chief Financial Officer.

To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company’s website at View Source. A recorded replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.

On September 8, 2024 r Astrazeneca reported results from an exploratory analysis of the TROPION-Lung01 Phase III trial showed TROP2 as measured by it’s proprietary computational pathology platform, quantitative continuous scoring (QCS), was predictive of clinical outcomes in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who were treated with datopotamab deruxtecan (Dato-DXd) (Press release, AstraZeneca, SEP 8, 2024, View Source [SID1234646406]). In patients with TROP2-QCS biomarker positive tumours, datopotamab deruxtecan demonstrated a meaningfully greater magnitude of efficacy versus docetaxel than in the overall trial population.

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!

These results will be featured in a Presidential Symposium (PL02.11) at the IASLC 2024 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer.

TROP2 is a protein broadly expressed in NSCLC on the surface of and inside tumour cells.1,2 When assessed using conventional immunohistochemistry (IHC)-based pathology, TROP2 expression has not been predictive of patient responses to TROP2-directed antibody drug conjugates (ADC).3,4 QCS is a fully supervised computational pathology platform, developed by AstraZeneca, that analyses digitised images of patient tissue samples and precisely quantifies targets, like TROP2, on and inside a tumour cell.

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd ADC discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.

In this analysis, QCS was used to analyse tissue samples collected from patients in TROPION-Lung01. This produced a normalised membrane ratio for each tumour cell in each sample. Patients’ tumours were considered TROP2-QCS biomarker positive if the majority (≥75%) of tumour cells exhibited a ratio below a predetermined value (≤0.56), indicating a greater proportion of TROP2 in the cytoplasm.

The analysis showed a greater proportion of patients with nonsquamous NSCLC were considered TROP2-QCS biomarker positive than those with squamous NSCLC (66% versus 44%, respectively). The threshold for biomarker positivity was optimised for progression-free survival (PFS) in the subgroup of patients with nonsquamous NSCLC without actionable genomic alterations because it represents a population with significant unmet medical need and without actionable biomarkers.

In patients with TROP2-QCS biomarker positive tumours (60% of the biomarker evaluable population including patients with nonsquamous and squamous NSCLC), datopotamab deruxtecan reduced the risk of disease progression or death by 43% versus docetaxel (median PFS of 6.9 versus 4.1 months; hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.41-0.79).

By comparison, in the primary analysis of the overall trial population, datopotamab deruxtecan reduced the risk of disease progression or death by 25% versus docetaxel (PFS of 4.4 versus 3.7 months; HR 0.75; 95% CI 0.62-0.91; p=0.004) as presented at the 2023 European Society for Medical Oncology Congress.5

In the subgroup of patients with nonsquamous NSCLC without actionable genomic alterations and with TROP2-QCS biomarker positive tumours, datopotamab deruxtecan reduced the risk of disease progression or death by 48% (PFS of 7.2 versus 4.1 months; HR 0.52; 95% CI 0.35-0.78).

Marina Garassino, MD, The University of Chicago, Professor of Medicine and investigator in the trial, said: "TROP2 is broadly expressed on solid tumour cells, including non-small cell lung cancer, but it has yet to be established as a predictive biomarker for any TROP2-directed antibody drug conjugate. We have shown with this analysis that the more precise quantitative measurement of TROP2 on and inside tumour cells, enabled by AstraZeneca’s computational pathology platform, can identify which patients with non-small cell lung cancer are most likely to benefit from treatment with datopotamab deruxtecan."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "This analysis demonstrates the power of our computational pathology platform to discover new predictive biomarkers and substantially improve patient selection for datopotamab deruxtecan. It also has great potential to help more precisely select patients across our broader antibody drug conjugate portfolio. ​We are excited to extend our collaboration with Roche Tissue Diagnostics with the aim of validating this exploratory approach for TROP2, developing the companion diagnostic and bringing it to the clinic as quickly as possible."

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: "The results from the QCS analysis support the potential of TROP2, as measured by quantitative continuous scoring, as a predictive biomarker for datopotamab deruxtecan and begin to answer the question of why certain patients with non-small cell lung cancer respond better to treatment. These insights are critical to advancing our understanding of how we can more precisely identify patients with non-small cell lung cancer who may benefit from treatment with our TROP2-directed antibody drug conjugate."

In the biomarker evaluable population, no new safety concerns were identified and rates of Grade 3 or higher treatment-related adverse events (TRAE) were similar regardless of TROP2 status. In patients with TROP2-QCS biomarker positive tumours, Grade 3 or higher TRAEs occurred in 30% and 46% of patients in the datopotamab deruxtecan and docetaxel arms, respectively. The most common Grade 3 or higher TRAEs were stomatitis (7%, 3%) and ocular surface events (3%, 0%). Grade 3 or higher adjudicated drug-related interstitial lung disease events occurred in 3% and 1% of patients in the datopotamab deruxtecan and docetaxel arms, respectively.

AstraZeneca and Roche Tissue Diagnostics collaborate to co-develop and commercialise the TROP2-QCS biomarker companion diagnostic

AstraZeneca and Roche Tissue Diagnostics are extending their existing collaboration to co-develop a novel companion diagnostic incorporating AstraZeneca’s proprietary computational pathology platform, QCS, which will be deployed within Roche’s navify Digital Pathology image management system.

Jill German, Head, Roche Tissue Diagnostics, said: "Our collaboration with AstraZeneca continues to push the boundaries of traditional cancer diagnostics. By developing an innovative Al tool that goes beyond human capabilities, the solution will be able to help determine which cancer patients are most likely to benefit from targeted therapies, potentially improving patient care."

Under this expanded collaboration, Roche Tissue Diagnostics and AstraZeneca will co-develop and commercialise a novel companion diagnostic in Roche’s navify Digital Pathology platform, based on the QCS computational pathology platform, to aid pathologists in interpreting an investigational VENTANA TROP2 assay.

As the leading provider of pathology lab solutions, Roche Tissue Diagnostics is delivering an end-to-end digital pathology workflow from tissue staining to producing high-quality digital images that can be reliably assessed using automated clinical image analysis algorithms.

Notes

Advanced non-small cell lung cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.6 NSCLC is the most common type of lung cancer, accounting for about 80% of cases.7 Approximately 75% and 25% of NSCLC tumours are of nonsquamous or squamous histology, respectively.8 While immunotherapy and targeted therapies have improved outcomes in the 1st-line metastatic setting, most patients eventually experience disease progression and receive chemotherapy.9-11 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects.9-11

TROP2 is a protein broadly expressed in the majority of NSCLC tumours.1 There is currently no TROP2-directed ADC approved for the treatment of lung cancer.12,13

TROPION-Lung01
TROPION-Lung01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus docetaxel (75mg/m2) in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.

The dual primary endpoints of TROPION-Lung01 are PFS as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, time to response, disease control rate as assessed by both BICR and investigator, and safety.

TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov.

Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer and HR-positive, HER2-negative breast cancer. The programme includes seven Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings.