On January 13, 2022 Castle Biosciences, Inc. (Nasdaq: CSTL), a leader in transforming disease management and improving patient outcomes through innovative diagnostics, reported the publication of clinical performance study data demonstrating that DecisionDx-SCC provides significant and independent prognostic value for stratifying metastasis risk in patients with cutaneous squamous cell carcinoma (SCC) with one or more risk factors (high risk) (Press release, Castle Biosciences, JAN 13, 2022, View Source [SID1234605469]). The study, titled "Enhanced Metastatic Risk Assessment in Cutaneous Squamous Cell Carcinoma with the 40-Gene Expression Profile Test," is available online in Future Oncology.

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!

"As the criteria for high-risk SCC is broad, it can be challenging for clinicians to appropriately manage a patient’s disease using only their clinicopathologic risk factors," said the study’s first author, Sherrif Ibrahim, M.D., Ph.D., dermatologist and Mohs surgeon at Rochester Dermatologic Surgery, Victor, New York, and associate professor, Department of Dermatology at University of Rochester Medical Center, Rochester, New York. "DecisionDx-SCC is designed to provide powerful prognostic information regarding a patient’s risk of metastasis, based on the biology of the individual patient’s tumor. As a physician, I rely on this information to help me make informed and personalized decisions in the management and follow-up care of patients with SCC."

Study background:

The annual incidence of SCC is high (approximately 2 million diagnosed cases/year in the U.S.) and continues to grow, resulting in a substantial number of patients with poor outcomes.
An estimated 200,000 patients per year with SCC are broadly classified as having high-risk disease, based on clinicopathologic factors associated with increased likelihood of poor outcomes; while these and other factors are used to stratify patient risk, low accuracy, histopathologic discordance and lack of standardized reporting limit clinical utility of this clinicopathologic factor-based approach.
DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of metastasis in patients with SCC with one or more risk factors.
The test result, in which patients are stratified into a Class 1 (low), 2A (moderate) or 2B (high) risk category, predicts individual metastatic risk to inform risk-appropriate management decisions.
Study methods and findings:

A retrospective cohort of 420 cases of primary SCC tumors with known patient outcomes underwent testing with DecisionDx-SCC; test results were assessed using Kaplan-Meier and Cox regression analyses with traditional clinicopathologic factor-based assessment, including National Comprehensive Cancer Network (NCCN) classification, and current staging methods, including Brigham and Women’s Hospital (BWH) and American Joint Committee on Cancer Eighth Edition (AJCC8) staging.
DecisionDx-SCC stratified the clinical validation cohort for metastatic risk: 212 cases received a Class 1 result (low risk), 185 cases received a Class 2A result (moderate risk) and 23 cases received a Class 2B result (high risk), with metastasis rates of 6.6%, 20.0% and 52.2%, respectively. Kaplan-Meier analyses demonstrated statistically significant differences in three-year metastasis-free survival (MFS) rates for the overall cohort; 93.9%, 80.5% and 47.8% for Class 1, Class 2A and Class 2B, respectively (log-rank, p<0.001). MFS rates were also significantly different across Class 1, Class 2A and Class 2B for subsets of the cohort with one risk factor and >2 risk factors.
DecisionDx-SCC further stratified risk within high-risk and very high-risk subgroups classified according to the current NCCN guidelines: for the high-risk subgroup, MFS rates were 95.9%, 84.3% and 62.5% for Class 1, Class 2A and Class 2B, respectively (p=0.0001); for the very high-risk subgroup, MFS rates were 89.6%, 75.9% and 40.0% for Class 1, Class 2A and Class 2B, respectively (p<0.001).
When compared to the accuracy metrics for AJCC8 and BWH T staging, the positive predictive value of a DecisionDx-SCC Class 2B result (high risk) was 52.2% compared to 30.0% and 39.9% for high-stage AJCC8 (T3/T4) and BWH (T2b/T3), respectively, while maintaining similar negative predictive value (87.2% compared to 88.5% and 87.9%, respectively).
The specificity of a DecisionDx-SCC Class 2B result (96.9%) and the sensitivity of a Class 2 result (77.8%) were significantly greater than the corresponding metrics for high-stage BWH and AJCC8. Together, these metrics demonstrated that DecisionDx-SCC identified tumors at high risk for metastasis with improved accuracy compared to BWH and AJCC8 tumor staging, while distinctly stratifying these cases from those with Class 1 tumors which have risk levels similar to the general SCC patient population.
The addition of DecisionDx-SCC results to binary T stage status identified subpopulations ranging from 5.7% to 71.4% (BWH) and 5.6% to 83.3% (AJCC8), compared to 12.1% to 33.9% (BWH) and 11.5% to 30.0% (AJCC8) for binary staging alone, which demonstrated that risk assessment was refined by combining DecisionDx-SCC results with tumor staging.
Overall, the data demonstrated that:
DecisionDx-SCC enhanced clinicopathologic risk factor-based assessment and identified a group of SCC patients within a high-risk cohort with metastasis rates similar to the general SCC population (Class 1 result with one risk factor).
Patients identified by DecisionDx-SCC as having the highest risk for metastasis (Class 2B) consistently had metastasis rates ≥50%, regardless of having one or two or more risk factors.
Combining DecisionDx-SCC with clinicopathologic factor-based risk assessment, regardless of whether it is based on risk factor count or T stage, further stratified risk for metastasis in SCC patients and improved the accuracy of risk predictions to better inform risk-appropriate patient management decisions.
About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1 (low), 2A (moderate) or 2B (high) risk category, predicts individual metastatic risk to inform risk-appropriate management.

Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

More information about the test and disease can be found at www.CastleTestInfo.com.

On January 13, 2022 Tempus, a leader in artificial intelligence and precision medicine, reported the commencement of an open label phase II study, in collaboration with GlaxoSmithKline (GSK) to evaluate the efficacy and safety of ZEJULA (niraparib), a poly (ADP-ribose) polymerase (PARP) inhibitor used for patients with advanced or metastatic solid tumors and a germline or somatic PALB2 mutation (Press release, Tempus, JAN 13, 2022, View Source [SID1234605468]). The study, titled "Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors" (the PAVO study, NCT05169437) is sponsored by Tempus and opened for enrollment on January 7, 2022.

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!

Patients with PALB2 mutations have been shown to be at an increased risk of being diagnosed with breast and pancreatic cancers1. Recent studies demonstrate that patients with metastatic breast and pancreatic cancers with germline PALB2 mutations have benefited from treatment with PARP inhibitors2. ZEJULA is an oral, once-daily PARP inhibitor approved by the FDA in 2017 for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. Phase 3 clinical trials are underway to evaluate the efficacy and safety of niraparib alone or in combination in additional solid tumors, including breast and lung cancers.

The PAVO study applies an innovative, data-driven approach designed to accelerate and streamline study timelines, and the signal-seeking process for niraparib. Additionally, Tempus leveraged its multi-modal dataset to expedite the protocol development and intelligent site selection in under 60 days.

The PAVO study is designed to enroll solid tumor patients with germline or somatic PALB2 mutations. Tempus is leveraging its TIME Trial Program, a just-in-time network of providers, to support rapid patient identification, site activation, and clinical trial enrollment. Under the study protocol, every patient sequenced through Tempus’ genomic sequencing platform will be pre-screened for PALB2 somatic and germline mutations.

"For this collaboration, our data produced insights led to the design of a new trial that we can expedite through our robust diagnostic and just-in-time trial network," said Dr. Kimberly Blackwell, Chief Medical Officer at Tempus. "We look forward to working together to evaluate niraparib’s potential for other populations who could benefit from this treatment."

1Hofstatter, Erin W, et al. "PALB2 Mutations in Familial Breast and Pancreatic Cancer." Familial Cancer, U.S. National Library of Medicine, June 2011, View Source

2Reiss KA;Mick R;O’Hara MH;Teitelbaum U;Karasic TB;Schneider C;Cowden S;Southwell T;Romeo J;Izgur N;Hannan ZM;Tondon R;Nathanson K;Vonderheide RH;Wattenberg MM;Beatty G;Domchek SM; "Phase II Study of Maintenance Rucaparib in Patients with Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in BRCA1, BRCA2, or palb2." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), U.S. National Library of Medicine, View Source

On January 13, 2022 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, and Helmholtz Munich (Helmholtz Zentrum München), reported a cooperation agreement for the clinical development of a radiopharmaceutical therapy candidate to treat malignant brain tumor glioblastoma (Press release, ITM Isotopen Technologien Munchen, JAN 13, 2022, View Source [SID1234605467]). ITM and Helmholtz Munich will collaborate to support an upcoming dose-escalation Phase I clinical trial with LuCaFab (ITM-31). LuCaFab is a CA XII-specific antibody Fab fragment targeting molecule, developed by Helmholtz Munich, radiolabeled with ITM’s medical radioisotope no-carrier-added lutetium-177 (n.c.a. 177Lu, EndolucinBeta). The planned multicenter investigator-initiated trial (IIT) will be led by the Westfälische Wilhelms-Universität Münster (University of Münster, Germany).

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!

Under the terms of the agreement, which formalizes an ongoing collaboration between ITM and Helmholtz Munich, ITM supports the logistics and supply of the clinical trial material and provides funding for the trial, which is designed for the treatment of up to 15 patients. ITM holds the exclusive option, which may be executed at any time, to license the compound, related worldwide patents and know-how for the manufacturing, use and application of LuCaFab from Helmholtz Munich under already agreed upon terms. The option also allows ITM to access and use trial data for research and commercial activities.

Steffen Schuster, CEO of ITM comments: "We are pleased to continue our collaboration with Helmholtz Munich and to further advance ITM’s clinical pipeline. Glioblastoma is among the most malignant and most difficult to treat cancers. A precise radionuclide therapy targeting an antigen highly expressed in glioblastoma, such as CAXII, may inhibit tumor growth after surgical removal. We are dedicated to clinically explore this opportunity for these patients who have such a high unmet medical need."

Reinhard Zeidler, Project Leader at Helmholtz Munich: "We believe that the combination of our tumor-specific targeting molecule and ITM’s medical radioisotope offers a new opportunity to improve the treatment of glioblastoma. After first encouraging studies with other radioisotopes in brain tumors, we expect ITM’s radioisotope lutetium-177 to have particularly favorable medicinal properties. Therefore, we look forward to initiating our collaborative clinical trial with the Departments of Neurosurgery and Nuclear Medicine at the University of Münster."

About Glioblastoma Multiforme

Glioblastoma is one of the most malignant types of primary brain tumors. It is a rare tumor, with about 3-5 new cases per 100,000 individuals per year.1 Even though surgery, chemotherapy, and radiotherapy have advanced over the last decade, resulting in a gradual improvement in the survival and quality of life of glioblastoma patients, the prognosis remains very poor.2 Glioblastoma is a complex tumor which is very difficult to treat. Surgery is rarely curative as the tumor cells infiltrate the surrounding tissue and the blood-brain barrier places a limitation on medical therapies. Even with macroscopic removal of the tumor and subsequent treatment with external beam radiation and chemotherapy, there is a risk that individual tumor cells will remain in the tissue and begin to grow again (relapse). More than 90% of tumor recurrences occur in the immediate vicinity of the primary tumor. Therefore, the treatment of the tissue surrounding the tumor is of great importance.

About LuCaFab (ITM-31)

Glioma cells can selectively express certain surface antigenic proteins such as carbonic anhydrase XII (CAXII), which are not found on healthy brain cells. Targeted molecules which specifically bind to the proteins can be produced to attack these antigens. This approach falls under the category of Targeted Radionuclide Therapy (TRT), an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing radiation exposure to normal tissue. Targeted radiopharmaceuticals are created by linking a therapeutic radioisotope to a targeting molecule that can precisely recognize tumor cells and bind to tumor-specific entities such as receptors expressed on the cell surface. The radioisotope accumulates at the tumor site and decays, releasing a therapeutic amount of ionizing radiation, thereby destroying tumor tissue. Helmholtz Munich has developed a new antibody binding fragment (Fab) against the CAXII antigen, which has been optimized for the treatment of glioblastoma. ITM’s no-carrier-added lutetium-177 (n.c.a. 177Lu, EndolucinBeta) is coupled to the antibody in order to selectively target and irradiate tumor cells. The resulting compound, LuCaFab (ITM-31), is administered via intracavitary injection, meaning it is applied directly into the tumor cavity following the surgical removal of the tumor to attack residual cancerous cells that lead to recurrent disease. LuCaFab thus acts as a complementary, adjuvant therapy to the current standard of care approach to glioblastoma as it is designed to be applied after initial treatment to prevent future tumor growth.

On January 13, 2022 EDAP TMS SA (Nasdaq: EDAP) ("the Company"), the global leader in robotic energy-based therapies, reported the publication of positive pre-clinical results using intraoperative high intensity focused ultrasound (HIFU) ablation of the pancreas in the peer-reviewed journal Cancers (Press release, EDAP TMS, JAN 13, 2022, View Source [SID1234605466]).

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 paper, entitled, Intraoperative HIFU Ablation of the Pancreas Using a Toroidal Transducer in a Porcine Model. The First Step towards a Clinical Treatment of Locally Advanced Pancreatic Cancer, describes a pre-clinical study designed to assess the feasibility of using HIFU under Doppler guidance to treat the pancreatic parenchyma and tissues surrounding the superior mesenteric vessels in vivo, in an animal model.

Pancreatic adenocarcinoma is among the most aggressive of all cancers. Regardless of treatment, the overall 5-year survival rate for patients with locally advanced pancreatic adenocarcinoma ("LAPA") is less than 5%. A HIFU approach could help in the treatment of such pathology that is inaccessible by other known therapeutic methods. Apart from palliative chemotherapy, no other curative options have been proven effective for the treatment of LAPA.

During the study, HIFU treatments were performed using an intraoperative HIFU probe which caused irreversible tissue necrosis in only a few seconds by producing sufficiently strong heat in the focal area. This study is the first step toward the launch of a Phase I study to evaluate the safety and feasibility of such a HIFU approach in patients with LAPA and to further confirm these encouraging results.

"The possibility of treating the pancreas using HIFU holds great promise for the treatment of locally advanced pancreatic cancers. If clinically successful, chemotherapy followed by HIFU treatment could rapidly become a novel treatment option of LAPA," concluded the paper’s authors.

Marc Oczachowski, EDAP’s Chairman and Chief Executive Officer, said: "We are very excited with these pre-clinical results and the promise they demonstrate for HIFU as a viable treatment for pancreatic cancer and other severe pathologies with low overall survival rates and no effective treatment options. We are proud of the ongoing work of the EDAP research team, who, together with Inserm and Centre Leon Bérard, are advancing the development of HIFU to offer patients a potentially effective treatment alternative for these difficult to treat cancers."

The full text of the paper can be found here.

On January 13, 2022 Amplia Therapeutics Limited (ASX: ATX) ("Amplia", the "Company") reported a GMP* manufacturing run of its clinical-stage drug candidate AMP945 has been successfully completed (Press release, Amplia Therapeutics, JAN 13, 2022, View Source;[email protected] [SID1234605465]). This provides additional drug substance to support toxicology studies and Phase 2 clinical trials in pancreatic cancer and lung fibrosis which are scheduled to start during 2022.

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!

Amplia’s contract manufacturing organisation (CMO) has successfully completed the manufacture of a 2 kg GMP batch of AMP945 within budget and on time. Previously, the maximum batch size of AMP945 that had been manufactured was 1 kg, meaning that the Company has now demonstrated a doubling of the scale at which AMP945 can be manufactured under GMP conditions. During the recently completed manufacturing run, the Company also implemented improvements to the manufacturing process for AMP945 that will support its future clinical and commercial development. Of note, long-term stability testing data has shown that AMP945 can be stored for periods of more than 24 months without detectable deterioration, an outcome that further supports commercial development of AMP945.

Amplia’s CEO, Dr John Lambert commented that "The successful doubling of our manufacturing capacity for clinical-grade AMP945 and the implementation of manufacturing improvements are outstanding outcomes which have exceeded our initial expectations. As well as providing material for our near-term development programs, these improvements lay a strong foundation for the AMP945 data package that will be required for future regulatory applications and its commercial development."

The Phase 2 clinical trial of AMP945 in patients with pancreatic cancer remains on track to commence during the current quarter. In addition, the extended (3-month) toxicology studies required to support the Phase 2 clinical trial of AMP945 in patients with fibrotic lung disease are on schedule to commence in February 2022 as previously advised.

* GMP: Good Manufacturing Practice

This ASX announcement was approved and authorised for release by the CEO of Amplia Therapeutics.