On February 15, 2022 Foundation Medicine, Inc., a pioneer in molecular profiling for cancer, reported that the U.S. Food and Drug Administration (FDA) has granted a Breakthrough Device designation for its circulating tumor DNA (ctDNA) detection and molecular monitoring assay, FoundationOneTracker (Press release, Foundation Medicine, FEB 15, 2022, View Source [SID1234608146]). The assay uses optimized algorithms for identifying patient-specific variants and a personalized assay design that allows for the detection of ctDNA in plasma. The Breakthrough Device designation was granted for the assay’s use in the detection of molecular residual disease, commonly known as MRD, in early-stage cancer after curative therapy. This molecular detection can help guide further therapy decisions depending on MRD status and an individual’s risk of relapse.

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!

Developed in partnership with Natera, FoundationOne Tracker uniquely combines Foundation Medicine’s tissue-based comprehensive genomic profiling (CGP) platform with Natera’s expertise in personalized ctDNA monitoring. The companies launched the research use only version of FoundationOne Tracker in June 2021, collaborating to support biopharma and academic partners with clinical trial and companion diagnostic planning.

In addition to the indications granted through the Breakthrough Device designation, FoundationOne Tracker’s personalized technology aims to address ctDNA detection and molecular monitoring in patients with both early- and advanced-stage cancers, including assessment of a patient’s response to therapy, as well as MRD detection, surveillance, and detection of molecular residual relapse following curative intent therapy.

"Foundation Medicine continues to shape the future of clinical care and research by helping oncologists and our industry partners find the answers they need to bring precision cancer care to patients," said Brian Alexander, M.D., M.P.H., chief executive officer at Foundation Medicine. "Personalized molecular disease monitoring enables early detection of ctDNA and can monitor for risk of relapse and track therapy response to help oncologists make personalized treatment plans for their patients. We are enthusiastic about our work to accelerate development of this assay so that it can more quickly impact care decisions in the clinic."

The FDA’s Breakthrough Devices Program is a voluntary program for certain medical devices and device-led combination products that provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions. The goal of the Program is to provide patients and health care providers with timely access to these medical devices by speeding up their development, assessment, and review, while preserving the statutory standards for premarket approval, 510(k) clearance, and De Novo marketing authorization, consistent with the FDA’s mission to protect and promote public health.

On the heels of data presented at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancer Symposium last month exploring the feasibility of MRD in metastatic colorectal patients who have undergone curative intent surgical resection, Foundation Medicine will also be presenting additional MRD data at the ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium on February 18 on the genomics of resected early-stage bladder cancer to validate CGP-informed MRD detection in ctDNA.

On February 15, 2022 Ambrx Biopharma Inc., or Ambrx (NYSE: AMAM), a clinical stage biopharmaceutical company using an expanded genetic code technology platform to create Engineered Precision Biologics, reported it received a "Study May Proceed" letter from the U.S. Food and Drug Administration (FDA) related to an Investigational New Drug (IND) application for ARX305, an antibody drug conjugate (ADC) designed to target CD70 to treat a broad range of solid and hematologic tumors such as renal cell carcinoma (Press release, Ambrx, FEB 15, 2022, View Source [SID1234608145]). ARX305 is the third ADC developed by Ambrx on its proprietary Engineered Precision Biologics platform that has received IND clearance.

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 clinical study cleared by the FDA, ARX305-01, is a first in human, Phase 1, multicenter, open-label, dose-escalation, and dose-expansion study to evaluate the safety, pharmacokinetics and preliminary anti-tumor activity of ARX305 in adults with clear cell renal cell carcinoma who are resistant or refractory to prior standard therapies.

ARX305 is an anti-CD70 ADC designed to target cancer cells displaying CD70, a protein expressed on a broad range of tumors including renal cell carcinoma, nasopharyngeal cancers, multiple myeloma, non-Hodgkin’s lymphoma and acute myeloid leukemia. Ambrx previously licensed the rights to develop and commercialize ARX305 in China to NovoCodex Pharmaceuticals Ltd. (NovoCodex).

"I am pleased with the milestones that we have reached on the development of antibody drug conjugates, marked by the filing and clearance of the IND application for ARX305, our third ADC program to reach this stage of development," said Feng Tian, Ph.D., Chairman of the Board, President, and CEO of Ambrx. "As we continue to explore potential indications for Ambrx’s proprietary ADC technology, the progression of ARX305 towards clinical trials targeting patients with various CD70 expressing tumors reinforces our confidence in the broad application of our platform."

On February 15, 2022 Ranok Therapeutics, a clinical-stage biopharmaceutical company that is developing a novel approach to targeted protein degradation for the treatment of cancer and other serious diseases, reported that Kevin P. Foley, Ph.D., Co-founder and Chief Scientific Officer of Ranok, will present at the virtual BMO BioPharma Spotlight Series: Proteins – Degraders and Other Next Gen Technologies on Thursday, February 24th at 10:10 AM ET (Press release, Ranok Therapeutics, FEB 15, 2022, View Source [SID1234608143]).

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!

Dr. Foley will review the company’s strategic vision and its first clinical program, RNK05047, a first-in-class, small-molecule, BRD4-selective protein degrader which was discovered and developed using Ranok’s proprietary approach to targeted protein degradation, CHAMP (Chaperone-mediated Protein Degradation). This technology leverages the company’s expertise in protein homeostasis and the cellular chaperone network to degrade disease-associated proteins, and is designed to increase drug safety and efficacy through selective targeting of disease tissues. The U.S. Food and Drug Administration (FDA) has cleared the company’s investigational new drug application (IND) for RNK05047 and enrollment of the Phase 1/2 study for patients with advanced solid tumors and lymphomas is expected to begin in the first half of 2022.

Following the presentation, a recording will be available for 3 months on Ranok’s website at: View Source

On February 15, 2022 Susan G Komen reported A first-of-its-kind tool may be able to help doctors better diagnose inflammatory breast cancer (IBC) (Press release, Susan G Komen, FEB 15, 2022, View Source [SID1234608142]). The novel tool and the findings of the analysis have been recently published in Breast Cancer Research and Treatment.

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 tool was developed through a collaborative effort between Susan G. Komen, the Inflammatory Breast Cancer Research Foundation and the Milburn Foundation, which brought together a team of leading breast cancer experts including clinicians, researchers and IBC patients.

"IBC has historically been difficult to diagnose and no changes to diagnostic approach have been made since the 1960’s. It is a rare and aggressive type of breast cancer that develops rapidly and can easily be confused with a breast infection and often goes underdiagnosed or misdiagnosed," said Dr. Reshma Jagsi, lead author, Komen Scholar and radiation oncologist.

Before the development of this tool, IBC lacked a formal, objective medical definition and diagnosis was often delayed, misdiagnosed or missed. IBC usually presents as swelling or redness of the breast, and not a lump, so it can be missed on a mammogram.

As the team began their work, it became evident that without a clear definition of IBC that included all the characteristics of this complicated disease, accelerating research would continue to be a significant challenge.

"If you want to study a disease, you have to ask, ‘What causes the disease and is this treatment better than that treatment?’ It’s harder to answer those questions if you haven’t clearly defined the disease," said Dr. Kathy Miller, senior author, Komen Scholar and medical oncologist. "It sounds so simple, but having a diagnosis really is the first step toward tackling the problem."

The group identified "defining characteristics" – including clinical, pathologic and imaging features – of IBC that led them to develop a quantitative scoring system for diagnosis. The system, or tool, is intended to increase diagnostic accuracy, predict outcomes, guide treatment decisions and inclusion criteria for clinical trials.

This tool will also enable researchers to study the biology of IBC and make discoveries to advance progress towards personalized care for all breast cancer patients.

"Komen has been able to see further into the future about how this definition isn’t just about writing something in a dictionary. This is about something that is essential to undergird future research," added Jagsi.

IBC is aggressive and can spread quickly, resulting in approximately 30 percent of patients being diagnosed at stage IV, or with metastatic disease, meaning their breast cancer has already spread to other parts of their body.

Susan G. Komen, the Inflammatory Breast Cancer Research Foundation and Milburn Foundation raised more than $1.4 million in a fundraising campaign last year to support the IBC cohort and the research that was recently published.

"With aggressive breast cancers like IBC, patients need more treatment options, and they need them now. This collaboration is helping us get closer to finding more effective treatments for a type of breast cancer that is difficult to diagnose and treat," said Victoria Wolodzko, Senior Vice President of Mission at Susan G. Komen.

"This partnership illustrates our continued leadership in funding critical IBC research," said Bryon Davis, CEO of the Milburn Foundation. "The impressive results of our campaign have helped us reach this key milestone. Working with Susan G. Komen and the Inflammatory Breast Cancer Research Foundation, we brought together an exceptional team to help define a path forward in the fight against IBC."

"Patient advocacy is about taking an active role in defining the critical conversations that will accelerate research discoveries and drive results for patients," said Ginny Mason, Executive Director of the Inflammatory Breast Cancer Foundation. "In our more than 20 years of work in IBC patient advocacy and research, this partnership with Susan G. Komen and Milburn is critical to push key issues forward."

Susan G. Komen, the Inflammatory Breast Cancer Research Foundation and Milburn Foundation continue to raise funds to support ongoing research studies to validate the new scoring system.

The next step is to perform further studies to validate the scoring system.

Co-authors along with Dr. Jagsi and Dr. Miller include: G. Mason, B.A. Overmoyer, W.A. Woodward, S. Badve, R.J. Schneider, J.E. Lang, M. Alpaugh, K.P. Williams, D. Vaught, A. Smith and K. Smith.

On February 15, 2022 Blue Earth Diagnostics, a Bracco company and recognized leader in the development and commercialization of innovative PET radiopharmaceuticals, reported publication of key results from its Phase 3 SPOTLIGHT trial of 18F-rhPSMA-7.3 in recurrent prostate cancer in an abstract being presented at the ASCO (Free ASCO Whitepaper) 2022 Genitourinary Cancers Symposium (ASCO GU) (Press release, Blue Earth Diagnostics, FEB 15, 2022, View Source [SID1234608141]). 18F-rhPSMA-7.3 is an investigational Prostate-Specific Membrane Antigen-targeted radiohybrid (rh) PET imaging agent. The SPOTLIGHT study (NCT04186845) is a Phase 3, multi-center, single-arm imaging study, conducted in the United States and Europe to evaluate the safety and diagnostic performance of 18F-rhPSMA-7.3 PET imaging in men with suspected prostate cancer recurrence based on elevated PSA following prior therapy.

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!

Based on the majority read results from the three blinded, independent PET readers, the overall detection rate (DR) of 18F-rhPSMA-7.3 PET in the SPOTLIGHT study was 83% (322/389). When stratified by PSA level, the DRs in the 305 patients with prior prostatectomy were: PSA <0.5 ng/mL: 64% (77/120); PSA ≥0.5 and <1 ng/mL: 76% (51/67); PSA ≥1 and <2 ng/mL: 93% (41/44); PSA ≥ 2 and <5 ng/mL: 96% (43/45); PSA ≥ 5 and <10 ng/mL: 88% (14/16); and PSA ≥10 ng/mL: 100% (13/13).

The study was designed to confirm positive 18F-rhPSMA-7.3 PET imaging findings using a composite Standard of Truth (SoT) consisting of either: histopathology (considered the gold standard); or conventional imaging (primarily with CT, bone scan or MRI, with fewer procedures using 18F-fluciclovine PET). In 366 men with a composite SoT (histopathology and/or conventional imaging), the patient-level Correct Detection Rate (CDR) was 57% (95% CI, 52-62). The region-level Positive Predictive Value (PPV) was 60% (55-65). However, in the subset of patients using the preferred gold standard of histopathology as the SoT (n=69), the patient-level CDR and region-level PPVs were much higher, at 81% (70-90) and 72% (63-81), respectively, providing important evidence regarding 18F-rhPSMA-7.3’s performance. Additional endpoints, including patient-level PPV and the percentage of patients upstaged by 18F-rhPSMA-7.3 PET, will be reported at future scientific meetings.

No serious adverse reactions were attributed to 18F-rhPSMA-7.3 PET in the SPOTLIGHT study. Overall, 16 (4.1%) patients had at least one treatment-emergent adverse event that was considered possibly related/related to 18F-rhPSMA-7.3. The most frequently reported events were: hypertension: 1.8% (n=7); diarrhea: 1.0% (n=4); injection site reaction: 0.5% (n=2), and headache: 0.5% (n=2).

The study will be discussed in an oral presentation at ASCO (Free ASCO Whitepaper) GU, "Detection rate of 18F-rhPSMA-7.3 PET in patients with suspected prostate cancer recurrence: Results from a phase 3, prospective, multicenter study (SPOTLIGHT)", by Dr. David M. Schuster, MD, FACR, Winship Cancer Institute of Emory University, in person and online at the conference on Thursday, February 17, 2022, at 7:00 PM ET. The ASCO (Free ASCO Whitepaper) GU program guide is available here.

"Up to 40% of patients who undergo radical prostatectomy, and up to 50% of patients who undergo radiation therapy will develop local or distant recurrences within 10 years, and the ability to determine the extent and location of recurrent prostate cancer to inform appropriate clinical management for these men is key for physicians and their patients," said David M. Schuster, MD, FACR, Emory University School of Medicine, and Coordinating Investigator for the SPOTLIGHT study. "Conventional imaging techniques have many limitations in prostate cancer identification and localization, and greater imaging accuracy is needed throughout the care continuum, to optimize therapeutic decision-making. The Phase 3 SPOTLIGHT study investigated the diagnostic performance of 18F-rhPSMA-7.3 PET imaging as a potential decision-making aid in assessing suspected biochemical recurrence of the disease. Taken together, we believe these strong results support the clinical utility of 18F-rhPSMA-7.3 PET in men with recurrent prostate cancer across a wide PSA range."

"We are pleased to share these key Phase 3 SPOTLIGHT study results with the clinical community at the prestigious ASCO (Free ASCO Whitepaper) GU 2022 conference," said David Gauden, D.Phil., President R&D and Chief Scientific Officer of Blue Earth Diagnostics. "SPOTLIGHT is the first of Blue Earth’s diagnostic imaging rhPSMA trials to report results, based on novel radiohybrid PSMA technology which offers potential theranostic utility in both diagnostic PET imaging and therapy. We look forward to sharing these convincing results with the U.S. Food and Drug Administration (FDA) as part of a New Drug Application for 18F-rhPSMA-7.3 PET imaging."

Dr. Gauden continued, "Blue Earth is committed to helping men with prostate cancer across the care continuum, and we particularly wish to thank the patients and clinical teams who participated in the SPOTLIGHT study, despite the many challenges COVID-19 presented. In working to fulfill our commitment to patients, we are working on a uniquely comprehensive prostate cancer portfolio, which includes 18F-fluciclovine as well as investigational rhPSMA compounds for potential use in diagnostic PET imaging and targeted radiopharmaceutical therapy. Early studies of 18F-rhPSMA-7.3 demonstrated high binding affinity for PSMA, together with biodistribution data suggesting the potential for low bladder activity. Our focus on 18F as the isotope of choice for PET imaging with rhPSMA was made in consideration of its spatial resolution and resulting high quality of PET images, and its physical half-life which greatly facilitates ease of large-scale manufacturing and distribution for broad-based patient access."

About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA)

rhPSMA compounds consist of a radiohybrid ("rh") Prostate-Specific Membrane Antigen-targeted receptor ligand which attaches to and is internalized by prostate cancer cells and they may be radiolabeled with 18F for PET imaging, or with isotopes such as 177Lu or 225Ac for therapeutic use – creating a true theranostic technology. The radiohybrid technology and rhPSMA originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA imaging technology from Scintomics GmbH in 2018, followed by acquisition of exclusive rights to therapeutic applications in 2020. Blue Earth Diagnostics has two Phase 3 clinical studies evaluating the safety and diagnostic performance of 18F-rhPSMA-7.3 PET imaging in prostate cancer: ("SPOTLIGHT," NCT04186845), in men with recurrent disease and ("LIGHTHOUSE," NCT04186819), in men with newly diagnosed prostate cancer. Currently, rhPSMA compounds have not received regulatory approval.