On May 26, 2021 TransThera Biosciences Co. Ltd. ( "TransThera" ), a clinical stage biotechnology company dedicated to developing innovative therapeutics across oncology, cardiovascular, and inflammatory diseases with major unmet medical needs globally and in China, reported that it has entered into a collaboration agreement with Roche to explore the combination of TT-00420 and atezolizumab for the treatment of patients in China with gastrointestinal ("GI") tract cancers (Press release, TransThera Biosciences, MAY 26, 2021, View Source [SID1234580649]). The Investigational New Drug application of the combination therapy has been recently approved by China National Medical Products Administration (NMPA).

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GI tract cancers represent one of the most challenging unmet medical needs in China. A lack of effective therapy calls for an emergent need for novel drug development. TT-00420, a unique small molecule kinase inhibitor, has demonstrated preliminary clinical benefits in Cholangiocarcinoma patients and other GI cancer patients in Phase I study. In addition to its targeted therapy attribute, TT-00420 also showed synergistic effect to modulate tumor microenvironment, rendering it a potential partner to checkpoint inhibitors for hard-to-treat solid tumors. Taken together, compelling pre-clinical and clinical data warrant the clinical development of TT-00420 in combination with atezolizumab.

"We are grateful to partner with Roche to tackle the challenge of GI tract cancers affecting people in China. GI cancers represent a huge unmet medical need and we are very excited about the potential of TT-00420 in this field. We are hoping to provide better options for GI cancer patients through the collaboration with Roche in the future", commented by Dr. Peng Peng, Vice President of TransThera in charge of the oncology pipeline development.

About TT-00420

TT-00420 is a highly innovative clinical stage spectrum-selective kinase inhibitor that exerts anti-tumor effects by targeting tumor cells and improving the tumor microenvironment. A large number of preclinical studies have found that TT-00420 has an excellent inhibitory effect on triple-negative breast cancer, cholangiocarcinoma and other malignant tumors. In September 2018, TT-00420 was approved by the US FDA for the first human clinical trial; in February 2019, it was approved by China’s NMPA for human clinical trials; and on November 7 of the same year, TT-00420 was granted the "Orphan Drug Designation" status (ODD) by FDA for the treatment of cholangiocarcinoma. On November 28, 2020, it was again approved by the US FDA targeting the clinical trial of new indication for cholangiocarcinoma. In March 2021, TransThera announced the completion of a phase I dose escalation clinical trial in China and the United States.

On May 26, 2021 Natera, Inc. (NASDAQ: NTRA), a pioneer and global leader in cell-free DNA testing, reported it will present new clinical data on its personalized and tumor-informed molecular residual disease (MRD) assay, Signatera, at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, taking place June 4-8, 2021 (Press release, Natera, MAY 26, 2021, View Source [SID1234580648]). Two additional studies were presented at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting that took place April 9-14, 2021.

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At ASCO (Free ASCO Whitepaper), Natera will present four posters highlighting the use of Signatera in new indications including multiple myeloma. It will also unveil new colorectal cancer data from the CIRCULATE-Japan trial, the largest prospective MRD study to date.

"We are proud to share this wealth of new data with the larger oncology community," said Alexey Aleshin, M.D., Natera’s vice president of medical affairs, oncology. "The quality and quantity of these real-world data is a testament to the power of Signatera’s tumor-informed and personalized technology and to Natera’s commitment to pushing the boundaries of our understanding of MRD."

Details about the ASCO (Free ASCO Whitepaper) abstracts are as follows:

Abstract #8029 | Poster Presentation | Presenter: Binod Dhakal, M.D.

Personalized ctDNA analysis to detect minimal residual disease and identify patients at high risk of relapse with multiple myeloma

A retrospective study on the feasibility of using Signatera for MRD assessment in multiple myeloma. Archival bone marrow aspirates and formalin-fixed, paraffin-embedded (FFPE) slides from 28 patients taken at the time of diagnosis were used to design the custom MRD assay for that individual. Patients were serially monitored for a median of 92.4 months after autologous stem cell transplantation (AHCT). Despite the low quality of the samples, the MRD-positive patients had a significantly higher rate of relapse and poorer recurrence-free survival than those who had no detectable MRD after AHCT (HR 5.6, 95% CI: 1.8 – 17, p= 0.0003).

"The variability in sampling of bone marrow aspirates often provides an inaccurate estimate of marrow MRD. Further, serial monitoring of MRD status using bone aspiration is challenging due to the invasive nature of the procedure," said Dr. Binod Dhakal, associate professor of medicine, the Medical College of Wisconsin, and first author of the study. "We are encouraged by the data from this study as it shows that a sensitive ctDNA test can provide a non-invasive alternative that captures the spatial heterogeneity of multiple myeloma."

Abstract #3608 | Poster Presentation | Presenter: Hiroki Yukami, M.D.

Minimal residual disease by circulating tumor DNA analysis for colorectal cancer patients receiving radical surgery: An initial report from CIRCULATE-Japan

CIRCULATE-Japan is the largest prospective MRD study to date. Initial analysis from the first 400 early-stage (stage II-III) or relapsed colorectal cancer (CRC) patients in this observational study shows that Signatera’s tumor-informed approach has a pre-surgical detection rate of >94% across stage I-III CRC patients, and a post-surgical relapse detection rate of 92% with longitudinal sampling. These detection rates compare favorably to longitudinal results from tissue-naive approaches. Additionally, the failure rate of patient samples using Signatera was very low at <3%.

Abstract #3540 | Poster Presentation | Presenter: Tenna V. Henriksen, M.S.

Serial circulating tumor DNA analysis for assessment of recurrence risk, benefit of adjuvant therapy, growth rate and early relapse detection in patients with stage III colorectal cancer

This study serially monitors 168 stage III CRC patients using Signatera for 36 months after surgery, during and after adjuvant chemotherapy, and during surveillance. It demonstrates, for the first time, that the quantitative measurement of ctDNA levels provided by Signatera can be used to assess the growth rates of metachronous metastases. Patients may be classified as having either a slow- or fast-growing tumor based on the rate of increase of ctDNA. Those with fast-growing tumors (137% increase per month) had significantly poorer overall survival compared to those with slow-growing tumors (27% increase per month), underscoring the clinical utility of ctDNA quantitation in the management of stage III CRC.

Abstract #4103 | Poster Presentation | Presenter: Pashtoon Kasi, M.D., M.S.

Tumor-informed assessment of circulating tumor DNA and its incorporation into practice for patients with hepatobiliary cancers

This exploratory study establishes the feasibility of using a tumor-informed MRD test in a heterogeneous cohort of 113 patients with hepatocellular carcinoma, cholangiocarcinoma and gallbladder cancer. Detection rates pre- and post-surgery, during treatment, and surveillance, are reported and shown to correlate with disease stage.

Details about the AACR (Free AACR Whitepaper) abstracts are as follows:

Abstract #552 | Poster Presentation | Presenter: Jocelyn Chapman, M.D.

Circulating tumor DNA predicts disease recurrence in ovarian cancer patients

This study demonstrates the prognostic value of ctDNA in 70 patients with stage I-IV epithelial ovarian cancer (EOC), in comparison to blood biomarker CA-125. The presence of ctDNA was observed to be a strong predictor of relapse (p<0.0001), while CA-125 was not significantly associated with relapse-free survival (p=0.09). ctDNA detection preceded radiological relapse by a median of 10 months (p<0.05), while CA-125 had a lead time of approximately one month.

Abstract #569 | Poster Presentation | Presenter: Antony Tin, Ph.D.

Correlation of variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors

This poster compares two common measures of tumor burden in cfDNA — variant allele frequency (VAF) and mean tumor molecules (MTM) per mL of plasma. 13,218 plasma samples from 6,265 patients with a wide range of cancer types were analyzed, and discordances between trends in VAF and MTM per mL were observed in 8.8% of samples. These samples were derived from patients who had high total levels of cfDNA due to increased cell death from ongoing treatment. In these scenarios, MTM per mL, which accounts for total cfDNA levels, was found to be more reflective of clinical truth, as confirmed by imaging.

About Signatera
Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for both clinical and research use, and has been granted three Breakthrough Device Designations by the FDA for multiple cancer types and indications. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. This maximizes accuracy for detecting the presence or absence of residual disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood. Signatera is intended to detect and quantify how much cancer is left in the body, to detect recurrence earlier and to help optimize treatment decisions.

The Signatera test performance has been clinically validated in multiple cancer types including colorectal, non-small cell lung, breast, and bladder cancers. Signatera has been developed and its performance characteristics determined by Natera, the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified.

On May 26, 2021 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that its senior management team will provide a company overview and business and financial updates at the Jefferies Virtual Healthcare Conference on Wednesday, June 2, 2021, at 1:00 p.m. ET / 6:00 p.m. IST (Press release, Jazz Pharmaceuticals, MAY 26, 2021, View Source [SID1234580647]).

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Interested parties may access the live webcast via the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com. A replay of the webcast will be archived on the website for at least one week.

On May 26, 2021 Foresee Pharmaceuticals (6576.TWO), ("Foresee") reported that the U.S. Food and Drug Administration (FDA) has approved the New Drug Application (NDA) for CAMCEVI 42 mg, a ready-to-use 6-month subcutaneous depot formulation of leuprolide mesylate, as a treatment of advanced prostate cancer (Press release, Foresee Pharmaceuticals, MAY 26, 2021, View Source [SID1234580646]).

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"The approval of CAMCEVI 42 mg is a significant step toward our mission in improving the standard of care and the lives of patients," said Dr. Ben Chien, founder and Chairman of Foresee. "It also demonstrates the success of Foresee’s pioneering Stabilized Injectable Formulation (SIF) technology. We want to thank the tireless work from the team and all stakeholders, which has made this approval possible.

The FDA approval was based on a successful Phase 3 study in 137 Advanced Prostate Carcinoma patients, where treatment with CAMCEVI 42 mg injection every 6 months was demonstrated to be effective, safe and well tolerated (most common adverse events listed below in ISI). The primary efficacy end point was the percentage of subjects with suppression of serum testosterone (≤50 ng/dl) by day 28 and from day 28 to day 336 in the intent-to-treat (ITT) population. The primary efficacy endpoint was successfully achieved in 97% of subjects, with mean testosterone concentration suppressed below castrate levels to 17.6 ng/dL on day 28.

CAMCEVI 42 mg injection is exclusively licensed to Accord BioPharma in the U.S. for commercialization. "Camcevi 42mg is an important addition to of the rapidly expanding Accord Biopharma oncology portfolio and provides clinicians an important option for the treatment of advanced prostate cancer," Said Chrys Kokino, U.S. President Accord BioPharma specialty products.

Important Safety Information for the U.S.

CAMCEVI 42 mg subcutaneous injection is a gonadotropin-releasing hormone (GnRH) agonist indicated for the treatment of adult patients with advanced prostate cancer. CAMCEVI is contraindicated in patients with hypersensitivity to GnRH, GnRH agonist analogs, or the components of CAMCEVI.

Patients may develop tumor flare during the first few weeks of treatment, which is a transient worsening of bone pain, uretral obstruction, spinal cord compression, or the occurrence of additional signs and symptoms of prostate cancer. Monitor patients closely and manage symptoms.

Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Blood glucose levels should be monitored and managed according to current clinical practice.

Increased risk of myocardial infarction, sudden cardiac death, and stroke has been reported in men receiving GnRH agonists. Patients should be monitored for cardiovascular disease and according to current clinical practice.

Androgen deprivation therapy may prolong the QT interval. Consider periodic monitoring of electrocardiograms and electrolytes.

Convulsions have been reported in patients receiving GnRH agonists, like CAMCEVI. Patients experiencing convulsions should be managed according to the current clinical practice.

Based on findings in animal studies and mechanism of action, CAMCEVI may cause fetal harm.

The most common (≥10%) adverse reactions were hot flush, hypertension, injection site reactions, upper respiratory tract infections, musculoskeletal pain, fatigue, and pain in extremity.

Please see the full prescribing information for CAMCEVI 42 mg for more information.

On May 26, 2021 Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and other indications, reported that the U.S. Food and Drug Administration (FDA) has accepted for priority review the Biologics License Application (BLA) submitted by Janssen Biotech, Inc. (Janssen) for ciltacabtagene autoleucel (cilta-cel), an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy (Press release, Legend Biotech, MAY 26, 2021, View Source [SID1234580645]). The Prescription Drug User Fee Act (PDUFA) target action date has been set for November 29, 2021.

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Priority review is usually granted to investigational therapies which, if approved, may offer significant improvements in the treatment, prevention or diagnosis of a serious condition. 1 Cilta-cel previously received Breakthrough Therapy Designation in December 2019, which is intended to expedite the development and review time for a potential new medicine. 2

"Cilta-cel has shown great promise in the treatment of patients with heavily pretreated multiple myeloma according to study findings reported to date. Today’s priority review designation marks another significant milestone for this cell therapy," said Ying Huang, PhD, CEO and CFO of Legend Biotech. "We look forward to our continued collaborative efforts with Janssen and in working with the FDA to bring this transformative therapy to patients who are in need of new treatment options."

The regulatory submission for cilta-cel is based on results from the pivotal Phase 1b/2 CARTITUDE-1 study which evaluated the efficacy and safety of cilta-cel in the treatment of patients with relapsed and/or refractory multiple myeloma. Updated longer term follow up data will be featured at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #8005) and European Hematology Association (EHA) (Free EHA Whitepaper)’s (EHA) (Free EHA Whitepaper) Virtual Congress (Abstract #EP964) next month.

About CARTITUDE-1

CARTITUDE-1 (NCT03548207) is a Phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of cilta-cel in adults with relapsed and/or refractory with multiple myeloma who have received at least 3 prior lines of therapy or are double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), received a PI, an IMiD, and anti-CD38 antibody and documented disease progression within 12 months of starting the most recent therapy.3 The primary objective of the Phase 1b portion of the study was to characterize the safety and confirm the recommended Phase 2 dose of cilta-cel, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). The Phase 2 portion further evaluated the efficacy of cilta-cel with overall response rate as the primary endpoint.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.4 Although treatment may result in remission, unfortunately, patients will most likely relapse.5 Relapsed myeloma is when the disease has returned after a period of initial, partial or complete remission and does not meet the definition of being refractory.6 Refractory multiple myeloma is when a patient’s disease is non-responsive or progresses within 60 days of their last therapy.7,8 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.9 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and few treatment options available.10

About Cilta-cel

Cilta-cel is an investigational chimeric antigen receptor T cell (CAR-T) therapy that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed or refractory multiple myeloma and in earlier lines of treatment. The design consists of a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies. In December 2017, Legend Biotech, Inc. entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. to develop and commercialize cilta-cel. In addition to a Breakthrough Therapy Designation granted in the U.S. in December 2019, cilta-cel received a PRIority MEdicines (PRiME) designation from the European Commission in April 2019, and a BTD in China in August 2020. Orphan Drug Designations were also granted for cilta-cel by the U.S. FDA in February 2019, and by the European Commission in February 2020. A Biologics License Application seeking approval of cilta-cel has been accepted by the U.S. FDA and a Marketing Authorisation Application has been accepted by the European Medicines Agency.