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.

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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.

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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.

On February 15, 2022 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for precision oncology, reported a strategic collaboration with the Moores Cancer Center at University of California San Diego Health, a National Cancer Institute-designated Comprehensive Cancer Center, to support clinical diagnostic testing in patients with advanced solid tumors and hematological malignancies (Press release, Personalis, FEB 15, 2022, View Source [SID1234608140]). The collaboration will bring Personalis’ leading comprehensive genomic tumor profiling test to UC San Diego health care professionals and their cancer patients to help guide FDA-approved therapy decisions, as well as clinical trial treatment options.

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"We are excited to collaborate with Moores Cancer Center to provide a comprehensive tumor immunogenomic profiling test to guide cancer patient treatment. This collaboration reaffirms our commitment to accelerate access to diagnostic testing for patients with advanced cancer, as well as to work with investigators to develop novel composite biomarkers to improve patient outcomes in the future," said Richard Chen, M.D., Chief Medical Officer and SVP of R&D of Personalis.

The Personalis test is one of the most advanced tumor profiling tests available today, providing full exome and transcriptome information across all human genes, and offering clinically important information to help identify appropriate therapies and clinical trials for individual cancer patients. The comprehensiveness of the test, and its unique ability to simultaneously characterize both tumor and immune genomics, will deliver better options for current cancer patients, while enabling UC San Diego and Personalis to work together on developing advanced composite biomarkers and on clinical research that may improve care in the future.

In addition to advanced biomarker work, the collaboration will include research studies for high sensitivity minimal residual disease (MRD) and cancer recurrence detection with a newly launched liquid biopsy assay. The Personalis liquid biopsy assay is designed to achieve MRD sensitivity down to the 1 part-per-million range, an approximately 10- to 100-fold improvement over other available technologies. This is expected to enable earlier detection across a broader variety of cancers and stages, including typically challenging early-stage cancers.

On February 15, 2022 Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global, clinical-stage biotechnology company developing and manufacturing novel therapies, reported that on Friday, February 11, 2022, the company was informed by the U.S Food and Drug Administration (FDA) via e-mail communication that its Phase 1 clinical trial for LB1901 has been placed on clinical hold (Press release, Legend Biotech, FEB 15, 2022, View Source [SID1234608139]). LB1901 is the company’s investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy targeting malignant CD4+ T-cells for the treatment of adults with relapsed or refractory T-cell lymphoma (TCL). The FDA indicated they will provide an official clinical hold letter to Legend Biotech by March 11, 2022.

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To date, one patient has been dosed in the clinical trial. Before receiving the FDA’s clinical hold communication, Legend Biotech had, in accordance with the protocol, paused the clinical trial due to low CD4+ T-cell counts in the patient’s peripheral blood and notified the FDA. The patient has not experienced drug-related serious adverse events (SAEs) and is being monitored in accordance with the protocol.

On February 15, 2022 Ipsen (Euronext: IPN; ADR: IPSEY) reported that two-year (25.4 months minimum; 32.9 months median) follow-up results from analyses of the Phase III CheckMate -9ER trial, which demonstrated sustained survival and response rate benefits (abstract #350)1, as well as health-related quality of life (HRQoL) improvements (abstract 323)2, with the combination of Cabometyx (cabozantinib) and Opdivo (nivolumab) versus sunitinib in the first-line treatment of advanced renal cell carcinoma (aRCC) (Press release, Ipsen, FEB 15, 2022, View Source;9ER-Trial [SID1234608138]). These updated results will be featured in two poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) from February 17 to 19, 2022.

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Dr. Cristina Suárez, M.D. PhD, Medical Oncologist at the Vall d´Hebron University Hospital, Barcelona, Spain and a lead investigator on the Phase III CheckMate -9ER trial said, "I am delighted to see the extent of the efficacy benefits demonstrated with the combination of Cabometyx and Opdivo in the CheckMate -9ER trial. These new data showcase the possibilities we can offer patients for their advanced disease, presenting the opportunity to significantly reduce their risk of death, and for some patients, achieve a complete response, whilst maintaining quality of life. There has been a dramatic evolution in the treatment landscape across lines of therapy for people living with renal cell carcinoma over recent years; this is an exciting time to be a treating physician in this area."

With a median follow-up of 32.9 months (25.4 months minimum), Cabometyx in combination with Opdivo continued to show superiority across efficacy endpoints of overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR), including increased complete response (CR) rates compared to sunitinib.1 For the secondary endpoint of median OS, the combination demonstrated a maintained clinically meaningful improvement (37.7 months vs. 34.3 months), with a 30% reduction in the risk of death (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.55 to 0.90) compared to sunitinib.1 PFS benefits, the primary endpoint of the study, were also maintained, with the combination continuing to double median PFS vs. sunitinib (16.6 months vs. 8.3 months, respectively; HR: 0.56; 95% CI: 0.46 to 0.68).1 Additionally, both superior ORR and DCR benefits were shown to be sustained with increased follow-up for the combination versus sunitinib; ORR 55.7% vs 28.4% and DCR 88.2% vs 69.3%. Moreover, among patients treated with the combination, 12.4% had a complete response vs 5.2% for sunitinib.1 In a further exploratory analysis of depth of response in target lesions by organ site, a higher percentage of patients experienced tumor shrinkage benefits with Cabometyx in combination with Opdivo vs. sunitinib across all organ sites assessed (kidney, liver, lung, lymph node and bone).1

The safety profile identified in the CheckMate -9ER trial was consistent with that previously observed for Cabometyx and Opdivo. 97.2% of patients treated with the combination experienced a treatment-related adverse event (TRAE) of any grade, compared to 93.1% of patients treated with sunitinib.1 Overall, 10.6% discontinued Opdivo only, 9.1% discontinued Cabometyx only, and 7.5% discontinued both Cabometyx and Opdivo (simultaneously or sequentially).1

In a separate analysis, with 32.9 months median follow-up, patients continued to report clinically meaningful HRQoL benefits with Cabometyx in combination with Opdivo compared to sunitinib.2 These exploratory outcomes were measured using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19) which assessed quality of life (QoL) associated specifically to kidney cancer as well as EQ-5D-3L instruments which assessed QoL more generally. HRQoL scores from these instruments were found to be improved or maintained over time amongst patients treated with the combination, while reductions in scores were observed with sunitinib. Additionally, those who received the combination were 48% less likely to be notably bothered by treatment side effects than patients in the sunitinib arm.2 These updated data follow the publication of 23.5 month median follow-up HRQoL data in The Lancet Oncology, published on 12 January 2022.3

Steven Hildemann, M.D. PhD, Executive Vice President, Chief Medical Officer, Head of Global Medical Affairs and Global Patient Safety, Ipsen said, "These new data from the CheckMate -9ER trial build on the previously demonstrated sustained efficacy benefits of the combination of Cabometyx and Opdivo, across patient risk groups. We are delighted to see that these extended survival benefits are further supported by a continued maintenance of health-related quality of life. Evaluating the patient perspective has been an integral element of the CheckMate -9ER trial analyses, ensuring that data are representative of the patient population and their priorities. With this growing body of evidence for the combination of Cabometyx and Opdivo, we are confident of the potential for these data to be realized in real world settings worldwide."

Ipsen thanks the patients and investigators involved in the CheckMate -9ER clinical trial.

ENDS

About renal cell carcinoma (RCC)
There were over 400,000 new cases of kidney cancer diagnosed worldwide in 2020.4 Of these, RCC is the most common type of kidney cancer, accounting for approximately 90% of cases.5,6 It is almost twice as common in men, and male patients account for over two thirds of deaths.4 If detected in the early stages, the five-year survival rate is high, but for people living with advanced or late-stage metastatic RCC, the survival rate is much lower, around 12%, with no identified cure for this disease.7,8

About the CheckMate -9ER trial
CheckMate -9ER was an open-label, randomized, multi-national Phase III trial evaluating people living with previously untreated advanced or metastatic RCC. A total of 651 patients (23% favorable risk, 58% intermediate risk, 20% poor risk; 25% PD-L1 ≥1%) were randomized to Cabometyx plus Opdivo (n= 323) versus sunitinib (n= 328). The primary endpoint is progression-free survival (PFS). The secondary endpoints include overall survival (OS) and objective response rate (ORR). The primary efficacy analysis compared the doublet combination versus sunitinib in all randomized patients. The trial was sponsored by Bristol Myers Squibb and Ono Pharmaceutical Co and co-funded by Exelixis, Ipsen and Takeda Pharmaceutical Company Limited.

About Cabometyx (cabozantinib)
In the U.S., Cabometyx tablets are approved for the treatment of patients with advanced renal cell carcinoma (RCC); for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib; for patients with advanced RCC as a first-line treatment in combination with nivolumab; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic DTC that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible. Outside the U.S., Cabometyx is currently approved in 60 countries, including in the European Union, Great Britain, Norway, Iceland, Australia, New Zealand, Switzerland, South Korea, Canada, Brazil, Taiwan, Hong Kong, Singapore, Macau, Jordan, Lebanon, the Russian Federation, Ukraine, Turkey, the United Arabic Emirates (U.A.E.), Saudi Arabia, Serbia, Israel, Mexico, Chile, Peru, Panama, Guatemala, the Dominican Republic, Ecuador, Thailand, Malaysia, Colombia and Egypt for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy; in the European Union, Great Britain, Norway, Iceland, Canada, Australia, New Zealand, Brazil, Taiwan, Hong Kong, Singapore, Lebanon, Jordan, the Russian Federation, Ukraine, Turkey, the U.A.E., Saudi Arabia, Israel, Serbia, Mexico, Chile, Peru, Panama, Guatemala, the Dominican Republic, Ecuador, Thailand, Egypt and Malaysia for previously untreated intermediate- or poor-risk advanced RCC; and in the European Union, Great Britain, Norway, Iceland, Canada, Australia, Switzerland, Saudi Arabia, Serbia, Israel, Taiwan, Hong Kong, South Korea, Singapore, Jordan, the Russian Federation, Ukraine, Turkey, Lebanon, the U.A.E., Peru, Panama, Guatemala, Chile, the Dominican Republic, Ecuador, Thailand, Brazil, New Zealand, Egypt and Malaysia for HCC in adults who have previously been treated with sorafenib. Cabometyx is also approved in combination with nivolumab as first-line treatment for people living with advanced RCC, in the European Union, Great Britain, Norway, Iceland, Switzerland, Taiwan, Singapore, the U.A.E., Australia, Chile, Israel and the Russian Federation.

The detailed recommendations for the use of Cabometyx are described in the Summary of Product Characteristics (EU SmPC) and in the U.S. Prescribing Information (USPI).

Ipsen has exclusive rights for the commercialization of Cabometyx outside the U.S. and Japan. Cabometyx is marketed by Exelixis, Inc. in the U.S. and by Takeda Pharmaceutical Company Limited in Japan. Cabometyx is a registered trademark of Exelixis, Inc.