On April 1, 2020 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to AFM13, its lead CD30- and CD16A-binding innate cell engager, for the treatment of patients with T-cell lymphoma (Press release, Affimed, APR 1, 2020, View Source [SID1234556107]). The granted designation includes peripheral T cell lymphoma (pTCL), a subtype of T-cell lymphoma. AFM13 is being investigated as a monotherapy for the treatment of relapsed or refractory CD30-positive pTCL in a Phase 2 registration-directed study.

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 FDA may grant orphan designation to drugs and biologics intended to treat a rare disease or condition affecting fewer than 200,000 persons in the U.S. The designation qualifies a company for certain benefits, including financial incentives to support clinical development and the potential for seven years of market exclusivity in the U.S. upon regulatory approval.

About AFM13
AFM13 is a first-in-class tetravalent, bispecific innate cell engager that specifically binds to CD30 on tumor cells and to CD16A on NK cells. AFM13 is being developed in peripheral T cell lymphoma (pTCL) and in other CD30-positive lymphomas. AFM13 has shown a favorable safety profile and signs of therapeutic efficacy as a monotherapy in CD30-positive non-Hodgkin lymphoma with cutaneous manifestation. In addition, data from a combination study of AFM13 with Merck’s anti-PD-1 antibody Keytruda (pembrolizumab) in Hodgkin lymphoma (HL) supports proof of principle for the combination of NK cell engagement with checkpoint inhibition. AFM13 has been granted orphan drug designation by the U.S. Food and Drug Administration for HL.

On April 1, 2020 Sysmex reported The "Prospective Study to Assess the Feasibility and Clinical Utility of Comprehensive Genomic Profiling at the Time of Initial Treatment in Patients with Solid Tumors" (the "Study"), which uses the OncoGuide NCC Oncopanel System1 (the "System", generic name: mutation analysis set for cancer genome profiling) developed through collaboration between the National Cancer Center (Location: Tokyo, Japan; President: Hitoshi Nakagama) and Sysmex Corporation (HQ: Kobe, Japan; Chairman and CEO: Hisashi Ietsugu), has been applied as Advanced Medical Care2 on April 1, 2020 (Press release, Sysmex, APR 1, 2020, View Source [SID1234556072]). The start date of this test will be announced on the website as soon as preparations at the National Cancer Center are completed. (View Source)

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 System analyzes genetic alterations in cancer-specific genes in patients with solid tumors and provides the cancer genomic profile of the tumor to help determine the treatment strategy, including accurate diagnosis and the selection of anti-cancer drugs. Currently, the System is covered by the National Health Insurance (NHI) in patients who have already undergone the standard treatment. Personalized genomic medicine based on cancer genomic profiling from an early phase at the time of initial treatment could provide the patients with more opportunities for appropriate treatment, including matched therapy. However, the feasibility and clinical utility of the System at the time of initial treatment remains unclear.

On April 1, 2020, the "Prospective Study to Assess the Feasibility and Clinical Utility of Comprehensive Genomic Profiling at the Time of Initial Treatment in Patients with Solid Tumors" has been applied as Advanced Medical Care. The National Cancer Center will announce the start date of this test at the National Cancer Center Hospital on its website as soon as the National Cancer Center is ready. (View Source).

The Study will include patients with six types of advanced or recurrent solid tumors, which could be treated with medication, including non-small-cell lung cancer, gastric cancer, colon cancer, breast cancer, pancreatic cancer, and biliary tract cancer (a total of 200 cases). We will evaluate whether personalized genomic medicine based on cancer genome profiling by the System at the time of initial treatment results in more opportunities of matched therapies compared to after standard treatment.

All collected samples will be analyzed at the Innovation Genome Center (Kawasaki Office) of RIKEN GENESIS Co., Ltd. (HQ: Tokyo, Japan; President and CEO: Naoto Kondo), a Sysmex subsidiary which provides lab assay services for gene analysis.

The National Cancer Center, Sysmex and RIKEN GENESIS will contribute to the implementation and development of personalized genomic medicine in Japan by providing high-value testing and diagnostic technologies for cancer patients.

Product Overview

Generic name: Gene mutation analysis set (for use in cancer genome profiling)

Name: OncoGuide NCC Oncopanel System (medical equipment production sales authorization number: 23000BZX00398000)

Target institutions: Medical institutions that have in place diagnostic systems appropriate for cancer genome profiling Target market: Japan

References

Press release dated December 25, 2018: "Sysmex Receives Manufacturing and Marketing Approval to Use the OncoGuide NCC Oncopanel System in Cancer Genome Profiling" View Source

Press release dated May 31, 2019: "The OncoGuide NCC Oncopanel System Receives Insurance Coverage for Use in Cancer Genome Profiling" View Source

Terminology
1 OncoGuide NCC Oncopanel System:
On December 25, 2018, Sysmex received manufacturing and marketing approval for the System as Japan’s first system for cancer genome profiling. This was also the first such system to be covered under the NHI, as of June 1, 2019.
The NHI coverage for D006-19 cancer genome profiling using the System includes patients with solid tumors for which no standard treatment exists and patients with solid tumors confirmed to have advanced locally or metastasized (including patients for which treatment is expected to conclude). Coverage is limited to cases in which the attending physician determines the potential for applying chemotherapy following this testing is high based on chemotherapy guidelines from related societies and the patient’s general status and organ function. The objective of Advanced Medical Care is to assess utility at the time of initial treatment.

2 Advanced Medical Care:
Refers to advanced healthcare technologies that have been approved by Japan’s Minister of Health, Labour and Welfare but are not yet covered by healthcare insurance. Based on a Fundamental Accord in December 2004 between the Minister of Health, Labour and Welfare; the Cabinet Officer Minister of State in Charge of Special Missions (regulatory reform, industrial revitalization); the minister in charge of administrative reform; and the Minister in charge of Special Zones for Structural Reform and Regional revitalization, this system was approved in combination with healthcare insurance coverage from the perspective of ensuring the safety of patients in Japan, preventing patient burdens from increasing, expanding patient choices, and increasing convenience.

On April 1, 2020 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, oncology therapeutics company developing onvansertib for the treatment of various cancers including colorectal, prostate and leukemia, reported that its Phase 1b/2 clinical trial of onvansertib in combination with standard-of-care FOLFIRI/Avastin (bevacizumab) for second-line treatment of patients with KRAS-mutated mCRC, will be featured in a presentation at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held from May 29 – June 2 (Press release, Trovagene, APR 1, 2020, View Source [SID1234556073]).

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!

There is a significant, unmet medical need to develop a safe and effective second-line treatment option for patients with KRAS-mutated mCRC. Currently available treatments have limited efficacy with only a 4% response rate and a median of 5.5 months progression-free survival (PFS). Other compounds currently in clinical development that target KRAS-mutated cancers have shown minimal activity in mCRC.

Data presented at the ASCO (Free ASCO Whitepaper)-GI meeting in late January showed the effectiveness of onvansertib against all prevalent KRAS mutations associated with mCRC by quantitative decreases in the plasma KRAS mutation levels in treated patients within the first cycle of treatment. Subsequent radiographic scans performed at 8 and 16 weeks confirmed efficacy by measurable shrinkage of tumors in all patients.

"We are excited to have our abstract accepted for presentation at the prestigious ASCO (Free ASCO Whitepaper) annual meeting," said Dr. Thomas Adams, Chief Executive Officer and Chairman of Trovagene. "Despite more than 30 years of intensive efforts, anti-KRAS therapies have remained elusive, and currently there are no drugs effectively targeting a broad spectrum of KRAS mutations. We believe onvansertib has the potential to provide a substantially improved treatment option for second-line treatment of patients with KRAS-mutated mCRC."

About the Phase 1b/2 Trial of Onvansertib in Metastatic KRAS-mutated Colorectal Cancer

The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second‑Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation (NCT03829410), will evaluate the safety and efficacy of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab). Up to 44 patients, with a confirmed KRAS mutation, metastatic and unresectable disease, who have failed or are intolerant of treatment with FOLFOX (fluoropyrimidine and oxaliplatin) with or without Avastin (bevacizumab), will be enrolled. The trial is being conducted at two prestigious cancer centers: USC Norris Comprehensive Cancer Center and The Mayo Cancer Center.

About Onvansertib

Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is over-expressed in multiple cancers including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a 24-hour half-life with only mild-to-moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Trovagene believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer.

Trovagene has three ongoing clinical trials of onvansertib: A Phase 2 trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga (NCT03414034); a Phase 1b/2 Study of onvansertib in combination with FOLFIRI and Avastin for second-line treatment in patients with mCRC with a KRAS mutation (NCT03829410); and a Phase 1b/2 clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML (NCT03303339). Onvansertib has been granted orphan drug designation by the FDA in the U.S. and by the EC in the European Union for the treatment of patients with AML.

Trovagene licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array (recently acquired by Pfizer), Ignyta (acquired by Roche) and Genentech.

On April 1, 2020 OSE Immunotherapeutics (ISIN: FR0012127173; Mnémo: OSE) reported that the primary endpoint was met in the predefined Step-1 analysis of its Phase 3 clinical trial of investigational product Tedopi, called Atalante 1, in HLAA2 positive non-small cell lung cancer (NSCLC) patients after failure from immune checkpoint inhibitors (PD-1/PD-L1) (Press release, OSE Immunotherapeutics, APR 1, 2020, View Source [SID1234556093]).

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!

Considering the population of the treated patients in both trial arms randomized at least 12 months before the time of the Step-1 analysis (N=99), the primary objective of Step-1 of the Atalante 1 trial planned in the protocol was met:

In the Phase 3 Step-1 analysis, the statistically positive preliminary results show at least 12-month survival for 29 patients out of 63 patients in the Tedopi arm, corresponding to a 12-month survival rate of 46% with the lower limit (33%) of the 95% confidence interval* [33%-59%], above the pre-specified futility boundary of 25%.

The observed rate of 46% is also above the assumption of a survival rate of 40% specified for the alternative efficacy hypothesis in the protocol.

In the chemotherapy control arm the results show at least 12-month survival for 13 patients out of 36 patients, corresponding to a 12-month survival rate of 36%.

Alexis Peyroles, CEO of OSE Immunotherapeutics, said: "We are very pleased with these positive results for Tedopi in Step-1 and with a 10% absolute difference in 12-month survival rate versus chemotherapy in NSCLC patients after failure of checkpoint inhibitor treated in Atalante 1 Step-1 trial. This outcome confirms the therapeutic value of our neoepitope product in a patient population for whom there are no registered product today and who needs new therapeutic options. Based on these positive results, we are now eager to engage in discussions with regulatory authorities to evaluate Tedopi’s current clinical results and agree upon the best options for further development to maximize on the product’s positive data in terms of benefit/risk ratio. In parallel, given the significant value added by positive Step-1 results, we continue exploring potential partnership opportunities for Tedopi."

As explained in the recent press release from March 26, 2020, the Company together with the Independent Data Monitoring Committee (IDMC) and the Steering Committee of the trial have reviewed the potential impact of the COVID-19 outbreak on the Atalante 1 trial. As of today, there is ongoing concern that trial data may be markedly impacted given the current worldwide COVID19 pandemic and the increased risk for patients with NSCLC as COVID-19 can cause serious pulmonary complications in this immunocompromised patient population. In addition, recommendations from several medical societies include voluntary holds on recruitment of new patients in oncology trials for the time being, due to patient safety concerns.

Consequently, following the recommendation from both IDMC and Steering Committee of Atalante 1, OSE Immunotherapeutics voluntarily decided to terminate patient screening and accrual in the initially planned and now cancelled Step-2. Further analysis of the positive Step-1 data will commence while engaging with regulatory agencies on the best development path forward for the product given the significant unmet medical need in the NSCLC patient population post-checkpoint inhibitor therapy failure.

*The 95% confidence interval (CI) is a range of values which has a 95% chance of containing the true value of the estimated parameter. With less rigor, it can be said that the CI represents the range of values within which it is 95% certain to find the true value sought. It provides a visualization of the uncertainty of the estimate.

On April 1, 2020 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the publication of a systematic review and meta-analysis of four study cohorts demonstrating that the DecisionDx-Melanoma test is an independent, significant predictor of recurrence and metastatic risk in patients with invasive cutaneous melanoma (Press release, Castle Biosciences, APR 1, 2020, View Source [SID1234556074]).

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 article titled, "Molecular risk prediction in cutaneous melanoma: a meta-analysis of the 31-gene expression profile prognostic test in 1,479 patients," appeared in the Journal of the American Academy of Dermatology (JAAD).

"This systematic review and meta-analysis are important because they further demonstrate the strength and consistency of the DecisionDx-Melanoma test as a significant, independent predictor of recurrence and metastasis in patients with Stage I-III melanoma, across these unique study cohorts," said lead author Bradley Greenhaw, M.D., Dermatology Center of North Mississippi, Tupelo, Mississippi. "The meta-analysis shows the value of using the DecisionDx-Melanoma gene expression profile test in combination with American Joint Committee on Cancer (AJCC) staging to optimize melanoma prognostication."

Systematic Review and Meta-Analysis Background:

This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)1.

Multiple published archival and prospective studies have described the prognostic capability, performance and clinical utility of the DecisionDx-Melanoma test to assess recurrence risk and inform patient management decisions on sentinel lymph node recommendations, follow up, surveillance imaging and referrals for patients with cutaneous melanoma.

This systematic review and meta-analysis were performed to evaluate the cumulative prognostic effect of the test across multiple cohorts with a focus on differences in recurrence and distant metastasis between patients with a DecisionDx-Melanoma Class 1A (lowest risk) and Class 2B (highest risk) test result. Four study cohorts, which included a total of 1,479 non-overlapping patients with Stage I-III melanoma, were included in the analysis.

Systematic Review and Meta-Analysis Results:

The DecisionDx-Melanoma test was found to be a consistent, independent and significant predictor of recurrence and metastatic risk in the meta-analysis across four study cohorts, achieving the highest Strength of Recommendation Taxonomy (SORT) level for a prognostic biomarker (Level 1 evidence).
The DecisionDx-Melanoma risk assessment is independent from other clinical factors (age, Breslow tumor thickness, ulceration and node status) and improves upon risk assessment performed with staging factors alone.
For melanoma recurrence, multivariate analysis showed that patients with DecisionDx-Melanoma Class 2B tumors are 2.90 times more likely (Hazard Ratio) to experience a recurrence than patients with Class 1A tumors (p<0.0001).
For distant metastasis, patients with Class 2B tumors are 2.75 times more likely to experience a distant metastasis than patients with Class 1A tumors (p<0.0001).
Despite differences in populations and study design, heterogeneity among the four studies was not significant.
The SORT system is used by the American Academy of Dermatology (AAD) and other organizations to evaluate the quality, quantity and consistency of evidence supporting tests such as DecisionDx-Melanoma. The SORT scale evaluates both the quality of the evidence (Level 1, 2 or 3) and strength of the recommendation (A, B or C).

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1600 patients. Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies that included more than 3,000 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Since its commercial launch in 2015, through December 31, 2019, DecisionDx-Melanoma has been ordered 51,967 times for use in patients with cutaneous melanoma.

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