On June 4, 2021 Agendia, Inc., a world leader in precision oncology for breast cancer, reported that new data from the first-of-its kind, national FLEX registry was debuted today at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Agendia, JUN 4, 2021, View Source [SID1234583584]).

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 FLEX study is led by clinicians across the United States and utilizes a shared study infrastructure to develop and investigate hypotheses for targeted patient subsets based on full transcriptome data, and annotated with over 800 clinical data elements. FLEX allows for diverse groups of patients and their physicians to participate in a clinical trial even if they are not living near a major research center.

"FLEX has continued to show its value in the enormous breadth of growing data we as oncologists and researchers can access," said Cynthia X. Ma, MD, PhD, oncologist and FLEX national PI at Washington University School of Medicine in St. Louis. "The collaborative nature of the registry gives physicians the chance to investigate the hypotheses formed in our real-world practices on a national level, to answer questions of both clinical importance and scientific interest. The depth and clinical significance of our findings are felt throughout the breast cancer community."

At the virtual ASCO (Free ASCO Whitepaper) 2021 conference, Agendia and its research collaborators provided a general update on the currently enrolling FLEX trial in a poster titled "The FLEX real-world data platform explores new gene expression profiles and investigator-initiated protocols in early stage breast cancer."

The power of FLEX to address relevant and pressing clinical questions was illustrated by data presented in a poster entitled "Whole transcriptome analysis comparing HR+ HER2- breast cancer tumors from patients <50 years and >50 years." The study showed that whole transcriptome analysis identified no substantial differences in gene expression between HR+/HER2- tumors in women with breast cancer, regardless of their age (over or under 50 years old). The data support the likely explanation that the apparent age-dependent benefit of chemotherapy in women younger than 50 with genomically Low Risk cancer, observed in recent trials, is not due to intrinsic biological differences in breast cancer, but rather to differences in the indirect effects of chemotherapy on the patient. These findings reinforce the essential need for shared decision making between a patient and her physician using the patient’s genomic expression profile as part of an informed treatment plan.

"We are excited to present an age-based analysis of the genomics in early stage breast cancer which has garnered so much attention in the last couple of years," said Cathy Graham, MD, FACS, Director of Breast Surgery, Glenn Family Breast Center of Winship Cancer Institute at Emory Saint Joseph’s Hospital, and first author of a FLEX poster focused on age-based analysis. "The trend that has emerged, which suggests that chemotherapy benefit seen in younger women may be a side effect of ovarian suppression – not necessarily the cytotoxic effects of the chemo on a tumor – is seen again in these results and must be considered when potentially less-aggressive alternatives are available."

Additional data of clinical significance for high risk ER+ breast cancer were presented by FLEX investigators including Joyce O’Shaughnessy, MD, Co-Chair of Breast Cancer Research and Chair of Breast Cancer Prevention Research at Baylor-Sammons Cancer Center and for The US Oncology Network, and a member of the Scientific Advisory Board for US Oncology Research Network, in the poster titled "Molecular profiles of genomically High Risk ER+ HER2- breast cancer tumors classified as functionally Basal or Luminal B by the 80-gene signature." This study outlined the identification by BluePrint of a subgroup of high risk ER+ tumors that are genomically Basal, and showed that analysis of whole transcriptome expression profiles reveals these cancers to be biologically closer to ER- Basal (and triple negative breast cancer) than ER+ Luminal cancers. ER+ Basal tumors may therefore require more aggressive treatment than ER+ Luminal tumors, confirming that BluePrint provides clinically actionable information beyond pathological subtyping and may guide neoadjuvant treatment decisions.

A further study from the FLEX database analyzed the correlation between a traditional poor prognosis pathology feature, lymphovascular invasion (LVI), and gene expression patterns. The study, titled "Gene expression associated with lymphovascular invasion and genomic risk in early-stage breast cancer," was presented by Nina D’Abreo, MD, medical director, breast program, Winthrop University Hospital, Perlmutter Cancer Center, and her colleagues, and showed that the potential prognostic information gained from the presence or absence of lymphovascular invasion (LVI) gene expression is likely already captured by MammaPrint and BluePrint. Importantly, presence or absence of LVI in MammaPrint Low Risk cancers was not associated with any discernible differences in whole transcriptome gene expression. LVI is currently excluded from most breast cancer clinical risk assessments, and while further studies will assess clinical outcomes, these data suggest that MammaPrint and BluePrint may be able to address a current gap in stratification of early stage breast cancers.

Agendia’s large-scale, prospective FLEX study continues to provide a rich source of data from real-world evidence in one of the most dynamic and inclusive study designs in breast cancer research to date, underscoring the company’s mission to help guide the diagnosis and personalized treatment of breast cancer for all patients.

On June 4, 2021 Agendia, Inc., a world leader in precision oncology for breast cancer, reported that an oral presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting revealed new data from the national FLEX registry that identify differences in tumor biology between ethnic groups that can lead to meaningful treatment decisions, reinforcing the need for appropriate representation of diverse patient populations in breast cancer studies (Press release, Agendia, JUN 4, 2021, View Source [SID1234583583]).

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!

A major theme of this year’s ASCO (Free ASCO Whitepaper) meeting centers around disparities in care and outcomes, which Agendia’s FLEX study aims to combat by prospectively enrolling 30,000 patients from various ethnicities, ages and demographic groups representative of the total breast cancer population. The data presentation from this study, "Disparities within Luminal breast cancer: clinical and molecular features of African American and non-Hispanic White patients," delivered by first author of the study Kent Hoskins, MD, Co-Leader of the Breast Cancer Research Group and Director of Cancer Genetics at the University of Illinois Cancer Center, details significant biological differences in luminal breast tumors from African American and non-Hispanic White women, suggesting that shared adverse socioeconomic exposures and/or genetic ancestry may be driving disproportionately aggressive tumor biology in African American women. This finding further underscores the need for inclusion of diverse patient groups in clinical trials to ensure equity in drug development.

"The data presented at ASCO (Free ASCO Whitepaper) 2021 show significant transcriptomic differences between Luminal tumors from African American and non-Hispanic White patients, seen even more starkly as our study controlled for age, obesity, and genomic classification," said Dr. Hoskins. "The data show ER+ breast cancers in African American women more often had upregulation of the mTOR pathway and cell cycle genes, which require different treatment approaches than other ER+ breast cancers. These data tell us that we desperately need proper representation of diverse populations in clinical trials, and future studies focused on the efficacy of these agents specifically in African American women with breast cancer, so that all patients can benefit from precision medicine, tailored to them, and accounting for their ancestry and genomic profiles."

Additional data from Agendia regarding breast cancer in African American women was shared in an abstract titled "Genomic risk classification by the 70-gene signature and 21-gene assay in African American, early-stage breast cancer patients." This study was triggered by recent research showing less accurate prognostic performance of OncotypeDX in African American women with early stage breast cancer. The abstract compared MammaPrint and OncotypeDX results in a cohort of African American women with ER+ breast cancer, and observed an overall discordance of 51% between the two tests in African American patients; notably, of tumors with a TAILORx intermediate risk score (11-25), 61% were classified as MammaPrint High Risk. Combined with previously published data in African American patients, 57% of OncotypeDX low risk score tumors are re-classified as MammaPrint High Risk, suggesting that OncotypeDX results could be less accurate in African American patients.

In addition, recent data indicate that African American patients who receive a low or intermediate OncotypeDX risk score have higher recurrence rates and lower survival than Caucasian patients with early stage breast cancer with the same risk score, a difference that can have meaningful clinical implications and requires further investigation.1

"It is essential that genomic tests either work consistently across diverse groups of patients, or have the ability to be calibrated to do so," said Patricia Robinson, MD, Associate Professor of Hematology and Oncology at Loyola University Medical Center, and Assistant Dean of Diversity, Equity and Inclusion at the Strich School of Medicine, "We cannot be using genomic tests that work for some people and not others, or accepting that the tests, which offer such crucial information, work better for some than for others. While the clinical evaluation of the discrepancy between OncotypeDX and MammaPrint may be ongoing, this data still captures the diversity of pathways driving tumor metastasis, and reinforces the importance of proper representation in trials and in test development and optimization."

Agendia’s large-scale, prospective FLEX registry continues to highlight data from real-world practices in one of the most flexible and inclusive studies in breast cancer research to date, playing an important part in the company’s mission to help guide the diagnosis and personalized treatment of breast cancer for all patients throughout their treatment journey.

On June 4, 2021 SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, reported initial results from its ongoing Phase 1 clinical trial of SQZ-PBMC-HPV demonstrating that the investigational cell therapy is safe and well-tolerated and can stimulate immune responses in certain patients with advanced or metastatic Human Papillomavirus positive (HPV16+) tumors (Press release, SQZ Biotech, JUN 4, 2021, View Source [SID1234583582]). The trial also showed that the company’s clinical stage manufacturing process of its autologous cell therapy is fast and reliable. The monotherapy stage trial data of the company’s first Antigen Presenting Cell (APC) platform candidate was presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting; poster presentation 2536.

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!

"Our vision is to make cell therapies that are safe and available with rapid turnaround times, allowing access to patients who need them," said Oliver Rosen, M.D., chief medical officer at SQZ Biotechnologies. "The company’s first-in-human data of a cell-based therapeutic vaccine are encouraging and an important first step towards validation of our directed immunity approach. Within this small trial of patients with very advanced disease, four patients who had progressed after multiple prior therapies achieved stable disease. These early outcomes, combined with encouraging safety data and fast clinical-scale manufacturing times, support our plans to initiate the trial’s safety combination phase with immune checkpoint inhibitors."

Safety & Tolerability

A primary outcome measure in the monotherapy dose escalation phase of the trial is safety and tolerability. Findings from the trial show that SQZ-PBMC-HPV was safe and well-tolerated at all tested dose levels with patients receiving 2 to 10 doses. No dose-limiting toxicities were observed.

"Overall, SQZ-PBMC-HPV has been safe and well tolerated by patients, even advanced patients as we have seen in this study," said study author Antonio Jimeno, M.D., Ph.D., Professor of Medicine, Oncology and Otolaryngology, University of Colorado School of Medicine, and Co-Leader, Development Therapeutics Program, University of Colorado Cancer Center. "I look forward to completing the single agent portion of the trial and advancing into the combinations of SQZ-PBMC-HPV with immunotherapies."

There were no grade 3 or higher treatment related serious adverse events (SAEs). In one patient, a grade 2 cytokine release syndrome and immune-related reaction was observed. A related grade 3 adverse event (AE, anemia) was observed in another patient.

Manufacturability

Manufacturing feasibility is a secondary outcome measure in the monotherapy phase of the trial. All patient batches were produced under current good manufacturing practice regulations, met specifications, and yielded multiple cryopreserved doses in less than 24 hours.

The findings show that doses of SQZ-PBMC-HPV were released and available for administration approximately one week from the time a patient’s cells were drawn. Antigen presentation was confirmed in all patient batches independent of individual patient medical history or prognostic score.

Patient Characteristics & Immune Response Biomarkers

The clinical trial enrolled patients with HPV16+ cancers progressing after unlimited prior lines of therapy. The 12 enrolled patients had very advanced disease:

Median number of prior cancer treatments was four with one patient having received seven prior treatments
Eleven patients previously treated with an immune checkpoint inhibitor (ICI)
Six of the 12 patients had a Royal Marsden Hospital (RMH) score of 2. (RMH scores range from 0-to-3, with scores of 2 and higher predicting poor prognosis and short life expectancy)
Despite the treatment refractory status of the enrolled patients, 4 out of 6 patients with RMH scores less than 2, reflecting less advanced disease, achieved stable disease as best overall response. Two of these patients showed an increase in CD8 tumor infiltrating lymphocytes (TILs), an important biomarker in immune-oncology therapy development.

The study authors highlighted two patients – Patients 2 and 7 detailed below – which suggested that less advanced patients with lower tumor burden, such as patient two, might have a higher likelihood of clinical benefit.

Patient 2: Enrolled 3-and-half years after diagnosis and had a best overall response of progressive disease with ICI therapy. The patient had an RMH score of 1 and low tumor burden. She achieved stable disease while on the SQZ-PBMC-HPV-101 trial and remained on study for over 10 months. Image analysis of the central tumor 28 days after the first dose showed a 2-fold increase in CD8 TILs on treatment compared to baseline
Patient 7: Enrolled 1 year after diagnosis and had a partial response with chemotherapy in combination with ICI therapy but then progressed. He achieved stable disease after treatment on the SQZ-PBMC-HPV-101 trial and remained on study for three months. Image analysis of the central tumor showed a 6-fold increase in CD8 TILs on treatment compared to baseline
The company is now actively enrolling patients in the last monotherapy highest-dose cohort of the Phase 1 trial. These results will inform the dosage approach for the combination therapy phase of the clinical trial with immune checkpoint inhibitors.

Poster Presentation Details

Title: Initial Results of a first-in-human, dose escalation study of a cell-based vaccine in HLA-A* 02+ patients with recurrent, locally advanced or metastatic HPV16+ solid tumors
First Author: Antonio Jimeno, M.D., Ph.D., University of Colorado Cancer Center
Abstract Number: 2536
Poster Session: Developmental Therapeutics — Immunotherapy
Date and Time: A copy of the poster is available on-demand via the ASCO (Free ASCO Whitepaper) virtual meeting website.

SQZ-PBMC-HPV-101 Trial Design

SQZ-PBMC-HPV is being evaluated in a Phase 1 clinical trial for the treatment of HPV16+ advanced or metastatic solid tumors. Patients must be positive for the human leukocyte antigen serotype HLA-A*02. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with immuno-oncology agents. The study’s primary outcome measures in the monotherapy and combination phases of the trial include safety and tolerability. Antitumor activity is a secondary outcome measure in both the monotherapy and combination stages of the trial, and manufacturing feasibility is a secondary outcome measure in the monotherapy phase of the trial. The monotherapy phase of the study includes escalating dose cohorts with a DLT window of 28 days and the definition of a recommended phase 2 dose. The planned safety combination phase of the study will include SQZ-PBMC-HPV and checkpoint inhibitors that have previously received regulatory approval. DLT will be measured over 42 days in the safety combination phase.

About Human Papillomavirus Positive Cancers

Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer HPV+ tumors account for 4.5% of all cancers worldwide, resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.

On June 4, 2021 Daiichi Sankyo Company, Limited reported that New data from patritumab deruxtecan (HER3-DXd), a HER3 directed antibody drug conjugate (ADC), demonstrated preliminary evidence of clinically meaningful and durable tumor response in patients with locally advanced or metastatic TKI-resistant, EGFR-mutated non-small cell lung cancer (NSCLC) (Press release, Daiichi Sankyo, JUN 4, 2021, View Source [SID1234583581]).

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 extended follow-up data from the dose escalation portion and one expansion cohort of a phase 1 study of patritumab deruxtecan were presented today during an oral presentation (Abstract #9007) at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (#ASCO21) Virtual Scientific Program.

While the efficacy of targeted therapy with EGFR TKIs is well-established in the treatment of patients with advanced EGFR-mutated NSCLC, the development of a broad range of resistance mechanisms commonly leads to disease progression.1,2 Subsequent salvage therapies after EGFR TKI and platinum-based chemotherapy have limited efficacy with progression-free survival (PFS) of approximately 2.8 to 3.2 months.2 New treatment approaches are needed to overcome resistance and improve survival in these patients.

An objective response rate (ORR), as assessed by blinded central review, was 39% (CI 95%; 26-52%) in 57 evaluable patients treated with patritumab deruxtecan (5.6 mg/kg). One confirmed complete response and 21 partial responses were observed. The disease control rate was 72% (CI 95%; 59-83%). After a median follow-up of 10.2 months (range, 5.2-19.9 months), the estimated median duration of response was 6.9 months (CI 95%; range, 3.1-NE months) and the estimated median PFS was 8.2 months (CI 95%; range, 4.4-8.3 months). Confirmed responses were observed in patients across a spectrum of baseline tumor HER3 membrane expression levels, EGFR activating mutations and EGFR TKI resistance mechanisms, including EGFR activating mutations (Ex19del, L858R, G719Y), other EGFR mutations (T790M, C797S, Ex20ins), amplifications (EGFR, CCNE1, MET) and non-EGFR mutations and fusions (MET, KRAS). A subgroup of patients treated with osimertinib and platinum-based chemotherapy (n=44) prior to enrollment in the study demonstrated similar efficacy. An ORR of 39% (CI 95%; 24-55%) and PFS of 8.2 months (CI 95%; 4.0-NE) was observed in this subgroup. Additionally, the confirmed ORR and median PFS were similar in patients with or without a history of brain metastases.

"EGFR TKIs are the standard of care for patients with advanced EGFR-mutated NSCLC. However, the activity of these agents is limited by the development of acquired resistance mechanisms," said Pasi A. Jänne, MD, PhD, Director, Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute. "In this study, where patients were heavily pre-treated, efficacy was observed in patients with and without known EGFR TKI resistance mechanisms in a population that is often difficult to treat. Targeting HER3 with patritumab deruxtecan may be a novel and promising strategy, and we look forward to further evaluating clinical activity and safety in the pivotal HERTHENA-Lung01 trial."

The safety profile of patritumab deruxtecan in patients treated with the 5.6 mg/kg dose (n=57) is consistent with that seen across all patients (n=81) in both the dose escalation and dose expansion cohort 1 of the study (doses range from 3.2 to 6.4 mg/kg). Grade 3 or higher treatment emergent events (TEAEs) occurred in 64% of all patients (n=81). TEAEs grade 3 or higher severity occurring in ≥ 5% of all patients were platelet count decreased, neutrophil count decreased, fatigue, anemia, dyspnea, febrile neutropenia, hypoxia, white blood cell count decreased, hypokalemia and lymphocyte count decreased. There were four cases of treatment-related interstitial lung disease (ILD) reported, as determined by an independent adjudication committee, including two of grade 1 severity, one grade 2, and one grade 3. The median time to adjudicated onset of treatment-related ILD was 53 days (range, 13-130 days). There were five TEAEs associated with death including two cases of disease progression, two cases of respiratory failure and one case of shock. All TEAEs associated with death were considered not related to the study drug.

"Treatment options that provide meaningful therapeutic benefit for patients with EGFR-mutated non-small cell lung cancer with disease progression following standard treatment with EGFR TKIs and platinum-based chemotherapy are limited," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "HER3 represents a novel target for therapeutic development as it is broadly expressed in non-small cell lung cancer. These results are encouraging since the safety profile was consistent with previous findings and response to patritumab deruxtecan was seen irrespective of the level of HER3 expression or mechanism of resistance to prior therapies."

Patients receiving 5.6 mg/kg (n=57) of patritumab deruxtecan were pre-treated with a median of four prior lines of therapy (range, 1-9), including EGFR TKIs (100%), platinum-based chemotherapy (91%) and immunotherapy (40%). A majority (86%) were previously treated with osimertinib. Of the 57 patients, 27 patients had brain metastases at baseline. As of data cut-off on September 24, 2020, 32% of patients remain on treatment with patritumab deruxtecan.

Summary of Results

Efficacy Measure

HER3-DXd Dose Escalation 5.6 mg/kg
Plus Dose Expansion 5.6 mg/kg (n=57) iv

Prior TKI±PBC
(n=57)

Prior OSI and PBC
(n=44)

ORR (%) (95% CI) i, ii

39% (26-52)

39% (24-55)

CR (%)

2%

2%

PR (%)

37%

36%

SD (%)

33%

30%

PD (%)

16%

18%

NE (%)

12%

14%

DCR (%) (95% CI)iii

72% (59-83)

68% (52-81)

Time to response (months)

2.6 months (1.2-5.4)

2.7 months (1.2-5.4)

Median DOR (months) (95% CI)

6.9 months (3.1-NE)

7.0 months (3.1-NE)

Median PFS (months) (95% CI)

8.2 months (4.4-8.3)

8.2 months (4.0-NE)

CI, confidence interval; CR, complete response; DCR, disease control rate; DOR, duration of response; OSI, osimertinib; NE, not estimable; PBC, platinum-based chemotherapy; PD, progressive disease; PR, partial response; PFS, progression-free survival; SD, stable disease; TKI; tyrosine kinase inhibitor
i As assessed by independent central review
ii ORR is (CR + PR)
iii DCR is (CR + PR + SD)
iv Median follow up: 10.2 (range, 5.2-19.9) months

About the Phase 1 Non-Small Cell Lung Cancer Study

The global, multicenter, open label, two-part phase 1 study is evaluating patritumab deruxtecan in previously treated patients with metastatic or unresectable NSCLC.

The dose escalation part of the study evaluated patients with EGFR-mutated disease either with progression on osimertinib or T790M-negative after progression on erlotinib, gefitinib or afatinib. The primary objective of this part of the study was to assess the safety and tolerability of patritumab deruxtecan and determine the recommended dose for expansion (RDE).

The dose expansion part of the study is evaluating patritumab deruxtecan at the RDE (5.6 mg/kg every three weeks) in three cohorts. Cohort 1 includes patients with locally advanced or metastatic EGFR-mutated NSCLC who experienced disease progression after taking one or more EGFR TKIs and one or more platinum based chemotherapy regimens. Cohort 2 includes patients with squamous or non-squamous NSCLC without EGFR-activating mutations following platinum-based chemotherapy and following an anti-PD-1 or anti-PD-L1 antibody regimen. Cohort 3 includes patients with NSCLC with EGFR-activating mutations including any histology other than combined small cell and non-small cell lung cancer; patients in Cohort 3 are randomized 1:1 to receive the 5.6 mg/kg RDE regimen (Cohort 3a) or an escalating up-titration regimen of patritumab deruxtecan (Cohort 3b).

Preliminary data from the dose escalation part of the study were presented previously at the 2019 World Conference on Lung Cancer, and early data from the dose escalation part (5.6 mg/kg dose) and Cohort 1 of the dose expansion were presented at the 2020 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress. Exploratory biomarker analyses assessing genomic alterations of patient tumors were presented at the 2020 World Conference on Lung Cancer.

The primary objective of the dose expansion part of the study is to assess efficacy of patritumab deruxtecan as measured by confirmed objective response rate assessed by blinded independent central review. Secondary study endpoints include investigator-assessed objective response rate; safety, tolerability and preliminary efficacy; and characterization of the pharmacokinetics of patritumab deruxtecan. The study enrolled patients at multiple sites in the U.S., Europe, Japan and other countries in Asia. For more information, visit ClinicalTrials.gov.

About Non-Small Cell Lung Cancer

Lung cancer is the most common cancer and the leading cause of cancer mortality worldwide. There were an estimated 2.2 million new cases of lung cancer and 1.8 million deaths in 2020.3 Most lung cancers are diagnosed at an advanced or metastatic stage.4 Non-small cell lung cancer (NSCLC) accounts for 80 to 85% of all lung cancers.5

The introduction of targeted therapies and checkpoint inhibitors in the past decade has improved the treatment landscape for patients with advanced or metastatic NSCLC; however, the prognosis is particularly poor among patients who have progressed after treatment with standard therapies. For patients who are not eligible for current treatments, or whose cancer continues to progress, new therapeutic approaches are needed.6

The mutationally-activated EGFR tyrosine kinase is a well-established oncogenic driver and molecular target for management of advanced stage NSCLC.7 For patients with advanced EGFR-mutated NSCLC, targeted therapy with EGFR TKIs offer higher response rates and progression-free survival compared to chemotherapy.7 However, most patients eventually develop resistance to these therapies, and standard treatment options are limited.8 Treatment options used in this setting historically have demonstrated limited efficacy with progression free survival of up to 6.4 months for platinum-based chemotherapy and 3.2 months for other salvage therapies.3,9 New treatment approaches are needed to overcome resistance and improve survival in these patients.

About HER3

HER3 is a member of the EGFR family of receptor tyrosine kinases, which are associated with aberrant cell proliferation and survival.10 Approximately 25 to 30% of lung cancers worldwide have an EGFR-activating mutation, and it is estimated that about 83% of all NSCLC tumors express the HER3 protein, which can be associated with an increased incidence of metastases, reduced survival and resistance to standard of care treatment.11,12,13 Currently, no HER3 directed medicines are approved for the treatment of cancer.

About Patritumab Deruxtecan

Patritumab deruxtecan (HER3-DXd) is one of three lead DXd ADCs in the oncology pipeline of Daiichi Sankyo. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, patritumab deruxtecan is comprised of a human anti-HER3 antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Patritumab deruxtecan is currently being evaluated in a comprehensive development program across multiple cancers as both a monotherapy and in combination with other anticancer treatments. The development program includes HERTHENA-Lung01, a pivotal phase 2 study in patients with locally advanced or metastatic EGFR-mutated NSCLC previously treated with a TKI and platinum-based chemotherapy; a phase 2 study in patients with advanced/metastatic colorectal cancer with disease progression following at least two prior lines of systemic therapy; a phase 1/2 study in HER3 expressing metastatic breast cancer; a phase 1 study in combination with osimertinib in locally advanced/metastatic EGFR-mutated NSCLC; and, a phase 1 study in previously treated patients with metastatic or unresectable NSCLC.

Patritumab deruxtecan is an investigational medicine that has not been approved for any indication in any country. Safety and efficacy have not been established.

On June 4, 2021 Agilent Technologies Inc. (NYSE: A) reported a presentation by Memorial Sloan Kettering Cancer Center (MSK) at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) to discuss the Resolution ctDx Lung, a laboratory-developed test (LDT) developed by Resolution Bioscience (Press release, Agilent, JUN 4, 2021, View Source [SID1234583580]).

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!

"Significantly, the study highlighted important differences between liquid biopsies and tissue testing, including faster turnaround to reporting, while providing the benefits of guided targeted therapy."

The presentation titled Overall survival with circulating tumor DNA-guided therapy in advanced non-small cell lung cancer will present evidence for the clinical utility of Resolution ctDx Lung in detecting actionable mutations in non-small cell lung cancer (NSCLC) patients.

Previous findings have supported the clinical utility of the Resolution ctDx Lung for accurately selecting patients for targeted therapies.1 The latest study, involving the largest prospective liquid biopsy cohort (>1,000 patients) with 3–4 years of survival data, demonstrates that cell-free DNA guided targeted therapies help result in better overall survival.

"This is the first and largest prospective study of ctDNA guided therapy to show an overall survival benefit in patients with lung cancers, providing evidence for the utility of liquid biopsy in clinical practice," said Bob Li, MD, PhD, MPH, Co-Director of the Thoracic Liquid Biopsy Program at MSK.

"This large cohort highlights the utility of the Resolution ctDx Lung in helping guide therapy selection to improve patient outcomes," said Mark Li, CEO of Resolution Bioscience, now a part of Agilent. "Significantly, the study highlighted important differences between liquid biopsies and tissue testing, including faster turnaround to reporting, while providing the benefits of guided targeted therapy."

The success of Resolution ctDx Lung further strengthens Agilent’s ability to deliver precision oncology testing assays for patients worldwide and demonstrates the company’s commitment as a partner in the development of powerful new clinical diagnostics solutions to expand the fight against cancer.

Resolution Bioscience is dedicated to developing a highly sensitive, non-invasive liquid biopsy platform that improves cancer diagnostics and monitoring for patients around the world. The company has developed core technology for circulating cell-free DNA NGS analysis. Resolution Bioscience’s Liquid Biopsy assays are powered by the company’s cell-free DNA (cfDNA) analysis platform, which includes targeted capture next-generation sequencing (NGS) biochemistry and tightly coupled, cloud-based bioinformatics. The Resolution Bioscience homologous recombination deficiency (HRD) assay has received Breakthrough Device Designation from the U.S. Food and Drug Administration.

References:

Sabari JK, Offin M, Stephens D, Ni A, Lee A, et al. (2019). A Prospective Study of Circulating Tumor DNA to Guide Matched Targeted Therapy in Lung Cancers. Journal Of The National Cancer Institute 111: 575-583. View Source PMID: 30496436