On March 4, 2019 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that Rubraca (rucaparib) is now available by prescription in Germany as monotherapy for the maintenance treatment of adults with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy (Press release, Clovis Oncology, MAR 4, 2019, View Source [SID1234533922]). In addition, Rubraca is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

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On January 24, 2019, the European Commission (EC) expanded rucaparib’s indication beyond its initial marketing authorization in Europe for the treatment of advanced ovarian cancer in selected patients granted in May 2018. With this label expansion, rucaparib is now approved as maintenance treatment for eligible patients regardless of their BRCA-mutation status. Rucaparib is the first PARP inhibitor licensed for an ovarian cancer treatment indication in the EU and is now the first to be available for both treatment and maintenance treatment among eligible patients.

"I have been treating women with relapsed ovarian cancer under the Rucaparib Access Program and I am confident that rucaparib represents an important treatment option for women here in Germany," "said Professor Jalid Sehouli, Gynecologic Oncologist and head of the Charité European Competence Center for Ovarian Cancer at the University of Berlin. "There has been a significant need for additional treatment options for women with relapsed ovarian cancer, and rucaparib’s approval in the maintenance setting provides another option for these patients."

"With this milestone approval in Germany, we are one step closer to ensuring that Rubraca is available to all eligible women who may potentially benefit," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "Rubraca has shown further tumor shrinkage as well as prolonged progression-free survival in this maintenance setting, therefore Rubraca represents an important step forward for women with advanced ovarian cancer, regardless of their BRCA status."

The EC authorization is based on data from the phase 3 ARIEL3 clinical trial, which found that rucaparib significantly improved progression-free survival in all ovarian cancer patient populations studied.i

The ARIEL3 trial was a double-blind, placebo-controlled clinical trial of rucaparib that enrolled 564 women with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer in complete or partial response to platinum-based chemotherapy. Patients were randomized (2:1) to receive rucaparib tablets 600mg twice daily (n=375) or placebo (n=189). i

ARIEL3 successfully achieved its primary endpoint of extending investigator-assessed progression-free survival (PFS) versus placebo in all patients treated (intention-to-treat [ITT]), population, regardless of BRCA status (median 10.8 mos vs 5.4 mos); the key secondary endpoint of extending PFS as assessed by independent radiological review (IRR) was also achieved (median 13.7 mos vs 5.4 mos). ii

In a prespecified exploratory analysis of patients in the ITT population with measurable disease at baseline showed a tumor response was reported in 18 percent of patients (n=26) on rucaparib compared to eight percent of patients (n=5) on placebo, including seven percent (n=10) in the rucaparib group who achieved a complete remission. i

The overall safety profile of rucaparib is based on data from 937 patients with ovarian cancer treated with rucaparib monotherapy in clinical trials. Adverse reactions occurring in ≥20% of patients were nausea, fatigue/asthenia, vomiting, anemia, abdominal pain, dysgeusia, alanine aminotransferase (ALT) elevations, aspartate aminotransferase (AST) elevations, decreased appetite, diarrhea, thrombocytopenia and creatinine elevations. The majority of adverse reactions were mild to moderate (Grade 1 or 2). ii

Grade ≥3 adverse reactions occurring in >5% of patients were anemia (23%), ALT elevations (10%), fatigue/asthenia (10%), neutropenia (8%), thrombocytopenia (6%), and nausea (5%). The only serious adverse reaction occurring in > 2% of patients was anemia (5%). ii

Adverse reactions that most commonly led to dose reduction or interruption were anemia (20%), fatigue/asthenia (18%), nausea (16%), thrombocytopenia (15%), and AST/ALT elevations (10%). Adverse reactions leading to permanent discontinuation occurred in 10% of patients, with thrombocytopenia, nausea, anemia, and fatigue/asthenia being the most frequent adverse reactions leading to permanent discontinuation.ii

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About Ovarian Cancer in Europe and Germany

In 2018, ovarian cancer was the sixth most common cancer among women in Europe, with an estimated 68,000 women diagnosed and the fifth leading cause of cancer deaths among women, with an estimated 45,000 deaths annually. After initial therapy, many women’s disease will still recur, and approximately 70% of patients with ovarian cancer will relapse within the first three years following initial treatment. Germany has the highest incidence of new cases and deaths caused by ovarian cancer in Europe. The World Health Organization estimates that in 2018 there were approximately 6,800 new cases of ovarian cancer and 5,400 ovarian cancer-related deaths in the country.

About Rubraca (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian, metastatic castration-resistant prostate, and bladder cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Clovis holds worldwide rights for Rubraca. Rubraca is an unlicensed medical product outside of the U.S. and the EU.

Rubraca (rucaparib) EU Authorized Use and Important Safety Information

Rucaparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Rucaparib is indicated as monotherapy treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA-mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Summary warnings and precautions: Haematological toxicity: Patients should not start rucaparib until they have recovered from haematological toxicities caused by previous chemotherapy (≤ CTCAE Grade 1). Complete blood count testing prior to starting treatment with rucaparib and monthly thereafter is advised. Rucaparib should be interrupted or dose reduced, and blood counts monitored weekly until recovery for the management of low blood counts. Myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML): If MDS/AML is suspected, the patient should be referred to a haematologist for further investigation. If MDS/AML is confirmed, rucaparib should be discontinued. Photosensitivity: Patients should avoid spending time in direct sunlight as they may burn more easily. When outdoors, patients should wear protective clothing and sunscreen with SPF of 50 or greater. Gastrointestinal toxicities: Low grade (CTCAE Grade 1 or 2) nausea and vomiting may be managed with dose reduction or interruption. Additionally, antiemetics may be considered for treatment or prophylaxis.

Click here to access the current Summary of Product Characteristics. Healthcare professionals should report any suspected adverse reactions via their national reporting systems.

On March 4, 2019 Castle Biosciences, Inc., a skin cancer diagnostics company providing personalized genomic information to improve cancer management decisions, reported three presentations at the 2019 American Academy of Dermatology (AAD) Annual Meeting held in Washington, DC from March 1-5 (Press release, Castle Biosciences, MAR 4, 2019, View Source [SID1234533938]).

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A meta-analysis of four DecisionDx-Melanoma studies including 1,479 patients titled, "Meta-Analysis of the Prognostic 31-Gene Expression Profile Test in 1479 Melanoma Cases," was presented during the Late-Breaking Research: Basic Science/Cutaneous Oncology/Pathology session. The study demonstrates that the DecisionDx-Melanoma test is an independent, significant predictor of recurrence and metastatic risk in a meta-analysis of four study cohorts.

DecisionDx-Melanoma Meta-Analysis

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 meta-analysis was 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 Class 1A (lowest risk) and Class 2B (highest risk) test result. Three published studies and one newly reported cohort including a total of 1,479 non-overlapping patients with Stage I-III melanoma were included in the analysis.

Key Study Findings:

The meta-analysis demonstrates that the DecisionDx-Melanoma test accurately identifies cutaneous melanoma patients who are at greater risk of metastasis with an effect that is consistent across multiple studies reaching the highest Strength of Recommendation Taxonomy (SORT) level for a prognostic biomarker (Level 1A evidence).
The DecisionDx-Melanoma test was found to be a consistent, independent and significant predictor of recurrence and metastatic risk in a meta-analysis of four study cohorts.
The DecisionDx-Melanoma risk assessment is independent from other clinical factors (age, Breslow tumor thickness, ulceration and node status).
Patients with Class 2B tumors are 2.83 times more likely to experience a recurrence than patients with Class 1A tumors (p<0.0001). Likewise, 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.
"This study is important because it demonstrates the strong and consistent effect of the DecisionDx-Melanoma test as a significant, independent predictor of recurrence and metastasis in patients with Stage I-III melanoma," said lead author Bradley Greenhaw, M.D., Dermatology Center of North Mississippi, Tupelo, Mississippi. "Across these four unique study cohorts, this meta-analysis shows that the highest level of evidence supports the use of the DecisionDx-Melanoma gene expression profile test to inform patient management decisions."

The SORT system is used by the 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). Using SORT ranking, a systematic review or meta-analysis of good quality studies or a prospective study with good follow-up represents the highest level of evidence (Level 1), and recommendations based on consistent, good quality evidence are deemed strongest (Strength of Recommendation: A).

Additional Castle Biosciences Data

DecisionDx-Melanoma Value in Stage IB-IIA Melanoma

A second study titled, "Improved Risk Assessment through Incorporation of a Prognostic 31-gene Expression Profile Test for AJCC Stage IB-IIA Cutaneous Melanoma," (Abstract 10597), which highlights the test’s accuracy in patients with Stage IB-IIA melanoma was presented as a poster at the AAD 2019 Annual Meeting.

Risk assessment is critical for guiding patient care decisions and treatment of cutaneous melanoma, especially for patients with Stage IB-IIA cutaneous melanoma who are considered for sentinel lymph node biopsy and adjuvant clinical trials. This study of 214 patients with Stage IB-IIA cutaneous melanoma from a previously published multicenter cohort with long-term outcomes assessed the use of AJCC staging combined with results from the DecisionDx-Melanoma test to improve recurrence risk prediction.

Key Study Findings:

Using AJCC staging alone, patients with Stage IB melanoma have an estimated 5-year melanoma specific survival (MSS) rate of 97%. Among these patients, those with a Class 1A (lowest risk) DecisionDx-Melanoma test result had an MSS rate of 98.6%, a risk equivalent to AJCC Stage IA. However, patients in this group who had a Class 2B (highest risk) test result had an 87.5% 5-year MSS rate. These risk estimates are lower than AJCC Stage IIIA disease.
Patients with Stage IIA cutaneous melanoma had an estimated 5-year MSS rate of 94% using AJCC staging alone. Patients in that group who had a Class 1A DecisionDx-Melanoma test result had an MSS rate of >99% (equivalent to Stage IA). Patients with a Class 2B test result had a 5-year MSS rate of 85.7%, similar to risk estimates for AJCC Stage IIIB.
As a group, Stage IB-IIA patients with a Class 1A result had significantly higher MSS, DMFS and RFS rates of 98.8%, 92.0% and 87.4% than those for patients with a Class 2B result (86.7%, 69.4% and 52%; p<0.01).
"Accurate risk assessment is important for clinical decision-making, especially for patients with Stage IB and IIA cutaneous melanoma who may be candidates for sentinel lymph node biopsy and adjuvant therapy clinical trials," commented study co-author Darrell S. Rigel, M.D., M.S., Clinical Professor at New York University School of Medicine. "These results show that use of the DecisionDx-Melanoma test further stratified patients into lower and higher risk groups following AJCC staging, supporting its value in developing individualized patient management plans and potentially future adjuvant therapy trials."

Update on cSCC Test Development

An update on the development of a cutaneous squamous cell carcinoma (cSCC) test was also presented at the AAD 2019 meeting as a poster (with oral discussion) titled, "Microarray Analysis to Identify Genes Associated with a High-Risk of Metastasis in Cutaneous Squamous Cell Carcinoma Tumors," (Abstract 10630). Many patients with cSCC will have a favorable prognosis, but a substantial number of them will experience metastasis or develop recurrences and die from their disease. The goal of this development program is to identify and validate a test that improves upon existing staging systems by identifying patients who have a relatively high risk for recurrence and enable more informed clinical management decisions.

As part of a larger archival development study, microarray analysis was performed on 80 recurrent and non-recurrent cases to identify novel genes associated with disease outcomes. Predictive modeling was performed to select and prioritize genes based on preliminary accuracy metrics for recurrence prediction. A subset of selected genes demonstrated positive correlation between microarray and qPCR analysis, suggesting feasibility in a clinical assay. Gene expression from microarray-identified targets will now be analyzed together with targets previously identified from the literature in order to optimize a prognostic signature.

Collaborative site recruitment and clinical trial activities for the cSCC test development program are actively continuing.

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 over 2,900 patients. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in three multicenter studies that have included 690 patients and have demonstrated consistent results. Performance has also been confirmed in five prospective studies including over 780 patients. The consistent high performance and accuracy demonstrated in these studies, which combined have included over 1,470 patients, provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies that included over 1,400 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in multicenter and single-center studies. More information about the test and disease can be found at www.SkinMelanoma.com.

About Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is one of the most common cancers. Approximately 200,000 patients are diagnosed with cSCC with high-risk features. Most patients have a favorable prognosis, but a subset of patients will develop metastasis and up to 15,000 patients each year die from their disease. As current staging parameters have a low positive predictive value, many more patients are considered high risk than actually develop metastatic disease. Conversely, many patients that develop metastatic disease are misidentified as low risk. This leads to over and undertreatment of a substantial number of cSCC patients. To address this clinical need, Castle Biosciences is developing a gene expression profile test to improve upon current staging systems and identify patients with cSCC at high risk for metastasis or recurrence, enabling more informed clinical decisions regarding adjuvant therapy and other management options.

On March 4, 2019 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported final results from the efficacy and safety data analysis of the prospective, randomized, single-blinded, controlled Phase 2b independent investigator-sponsored clinical trial of the combination of trastuzumab (Herceptin) +/- nelipepimut-S (NeuVax, NPS) targeting HER2 low-expressing breast cancer patient cohorts, including triple-negative breast cancer (TNBC) patients, which were presented at the 2019 ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium in San Francisco, CA (Press release, Sellas Life Sciences, MAR 4, 2019, View Source [SID1234533923]).

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The comprehensive findings are based on the final analysis of the full data-set from the clinical trial, and at a median follow-up of 25.7 months from the time of randomization. In the clinical trial, 275 patients were randomized to either placebo with granulocyte-macrophage colony-stimulating factor (GM-CSF) (n=139) or NPS with GM-CSF (n=136), while all received trastuzumab every 3 weeks for one year. No safety-related statistically significant differences were seen between the treatment and control arms in the rate of grade 1-3 adverse events of either local or systemic nature, while no grade 4/5 toxicities were observed in either arm. Also, there was no statistically significant difference between the treatment arms in the cardiac ejection fraction measured at baseline, as well as at four additional time-points up to 24 months post-randomization.

In the intent-to-treat (ITT) population (all HER2 low-expressing breast cancer patients; n=275), and over the 24-month post-randomization follow-up period, the disease-free survival (DFS) landmark rate was in favor of the combination (NPS plus trastuzumab) arm (89.8%) versus trastuzumab alone (83.8%), as shown in the graph below:

In the 97-patient TNBC cohort, the DFS landmark rate at 24 months for patients treated with NPS plus trastuzumab (n=53) was 92.6% compared to 70.2% for those treated with trastuzumab alone (n=44), a clinically and statistically significant improvement, as shown in the graph below:

In the TNBC cohort, there was a statistically significant reduction of 71.9% (p=0.01) in the frequency of clinically detected recurrences in those patients treated with the combination (NPS plus trastuzumab) versus trastuzumab alone.

"This final analysis of the study database establishes a clinically meaningful and statistically significant prolongation in DFS, a validated surrogate marker of overall survival for TNBC – by both hazard ratios and 24-month event rates – and a meaningful decrease in the frequency of relapses identified by standard clinical follow-up in favor of NPS plus trastuzumab given in the adjuvant setting in TNBC patients," commented Elizabeth A. Mittendorf, MD, PhD, Rob and Karen Hale Distinguished Chair in Surgical Oncology, Director of Research, Breast Surgical Oncology Brigham and Women’s Hospital, Director, Breast Immuno-Oncology Program Dana-Farber/Brigham and Women’s Cancer Center, and the Principal Investigator of the Phase 2b study.

Nicholas J. Sarlis, MD, PhD, Executive Vice President and Chief Medical Officer of SELLAS, further commented that "These definitive results provide us with an enhanced understanding of the clinical effect and safety profile of the combination therapy in this trial, with positive efficacy outcomes being essentially confined to TNBC patients, and continue to encourage us and support our ongoing discussions with the U.S. Food and Drug Administration on the most appropriate registration-enabling development path for NPS in TNBC."

The abstract text can be accessed at: View Source

Herceptin is a registered trademark of Genentech, Inc. and is not a trademark of SELLAS. The manufacturer of this brand is not affiliated with and does not endorse SELLAS or its products

On March 4, 2019 Seres Therapeutics, Inc. (NASDAQ:MCRB) reported that management will host a conference call and live audio webcast on March 6, 2019 at 8:30 a.m. ET to discuss fourth quarter and full year 2018 results and provide a general business update (Press release, Seres Therapeutics, MAR 4, 2019, View Source [SID1234533939]).

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To access the conference call, please dial 844-277-9450 (domestic) or 336-525-7139 (international) and reference the conference ID number 6566237. To join the live webcast, please visit the "Investors and Media" section of the Seres website at www.serestherapeutics.com.

A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for approximately 21 days.

On March 4, 2019 Immunomic Therapeutics, Inc. reported that a poster will be presented by Immunomic scientists at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 to be held in Atlanta, Georgia from March 29-April 3, 2019 (Press release, Immunomic Therapeutics, MAR 4, 2019, View Source [SID1234533924]).

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The poster will be presented during the meeting in a late-breaking poster session with preclinical data relating to Immunomic’s investigational DNA vaccine, ITI-7000.

Presentation details are as follows:

Poster Title: DNA vaccine co-expressing Her2/ErbB2 antigen, fused with LAMP, elicits strong antitumor effects in vivo by increasing tumor infiltration with CD8+ T cells
Session Category: Immunology
Session Title: Late-Breaking Research: Immunology 2
Session Date and Time: Tuesday, April 2, 2019 8:00 AM- 12:00 PM
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 42

About UNITE

ITI’s investigational UNITE platform, or UNiversal Intracellular Targeted Expression, is thought to work by encoding the Lysosomal Associated Membrane Protein, an endogenous protein in humans. In this way, ITI’s vaccines (DNA or RNA) have the potential to utilize the body’s natural biochemistry to develop a broad immune response including antibody production, cytokine release and critical immunological memory. This approach could put UNITE technology at the crossroads of immunotherapies in a number of illnesses, including cancer, allergy and infectious diseases. UNITE is currently being employed in Phase II clinical trials as a cancer immunotherapy. ITI is also collaborating with academic centers and biotechnology companies to study the use of UNITE in cancer types of high mortality, including cases where there are limited treatment options like glioblastoma and acute myeloid leukemia. ITI believes that these early clinical studies may provide a proof of concept for UNITE therapy in cancer, and if successful, set the stage for future studies, including combinations in these tumor types and others. Preclinical data is currently being developed to explore whether LAMP nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses to tumor types that otherwise do not provoke an immune response.