2021 – Page 835 – 1stOncology™: Cancer Intelligence Service

Natera Releases New Clinical Data at ESMO 2021 in Gastroesophageal Cancer and Uveal Melanoma

On September 17, 2021 Natera, Inc. (NASDAQ: NTRA), a leader in cell-free DNA testing, reported new data being presented by the company and its collaborators on the use of the Signatera personalized molecular residual disease (MRD) technology at the 2021 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, taking place September 16–21, 2021 (Press release, Natera, SEP 17, 2021, View Source [SID1234587911]).

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In three new studies, Natera will present the real-world clinical performance of Signatera in esophageal and gastric cancers, the power of ctDNA dynamics for assessing treatment response in uveal melanoma and the correlation of CHIP mutations with patient outcomes.

"Results from our study indicate that ctDNA is highly predictive of relapse in patients with gastroesophageal cancer," said Brandon Huffman, M.D., clinical oncology fellow at Dana Farber Cancer Institute and Massachusetts General Hospital Cancer Center, and first author of the study. "Most gastroesophageal cancers recur after definitive treatment, and patients with advanced disease have a poor overall prognosis. This study addresses a huge need for tools to better identify patients at risk of recurrence and to inform disease management."

"This data underscores the value of tumor-informed MRD assessment in GI cancers," said Alexey Aleshin, M.D., Natera’s VP of medical affairs, oncology. "It also highlights the potential for Signatera to improve upon radiographic imaging as a clinical endpoint, which can accelerate drug development and improve patient care."

Details about the presentations are as follows:

Performance of a tumor-informed circulating tumor DNA assay from over 260 patients with over 800 plasma time points in esophageal and gastric cancer
On-Demand ePoster: 1415P
Presenter: Griffin L. Budde, Natera, Inc.

This study used Signatera for the detection and quantification of ctDNA in a prospective real-world cohort of 886 plasma samples from 269 patients with gastroesophageal cancer. Serial time points were collected in a subset of patients to monitor ctDNA levels after curative intent therapy. Analysis showed tumor-informed ctDNA status is highly predictive of relapse in patients with stage I-IV disease, with ctDNA detected in 93.3% of samples at baseline.

Early reduction in ctDNA, regardless of best RECIST response, is associated with overall survival (OS) on tebentafusp in previously treated metastatic uveal melanoma (mUM) patients
Mini Oral Presentation: 1757O
Presenter: Alexander Shoushtari, M.D.
Date: Sunday, September 19, 2021, 13:40 CEST

Uveal melanoma is a rare type of melanoma of the eye, associated with frequent liver metastases. This study of 127 mUM patients used a custom ctDNA assay for the evaluation of tebentasfusp therapy. Baseline ctDNA levels significantly correlated with tumor burden, and by week 9, 70% of evaluable patients showed ctDNA reduction associated with greater mean tumor shrinkage. For tebentafusp, ctDNA reduction appeared more correlated with overall survival than RECIST response.

Association of clonal hematopoiesis of indeterminate potential with higher risk of disease progression
On-Demand ePoster: 1762P
Presenter: Derek Klarin, M.D.

Buffy coat samples derived from 2484 patients diagnosed with colorectal, breast, lung and other solid cancers were analyzed for the presence of CHIP mutations, which were detected in 16% of patients, with the majority having a single mutation. As expected, the frequency of CHIP increased with age and reached 20% in patients above 60 years, who were also more likely to have multiple CHIP variants compared to the younger patients. Although CHIP mutations are not tumor-derived and should not be used to monitor MRD burden, the presence of CHIP in MRD-positive cases was associated with poor patient outcomes and reduced time to recurrence.

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 Signatera’s 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.

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.

Lunit AI Applied to Clinical Trial for Drug Development for the First Time–Findings Presented at ESMO 2021

On September 17, 2021 Lunit reported that its AI for tissue analysis has been applied in a clinical trial for drug development, accurately predicting the patients’ response to immunotherapy (Press release, Lunit, SEP 17, 2021, View Source;findings-presented-at-esmo-2021-301379353.html [SID1234587910]). Including this major finding, the company presented three studies at European Society for Medical Oncology(ESMO) Congress 2021.

Lunit has been focusing on developing novel AI biomarkers that can be applied in cancer treatment. Since 2019, it has been validating the effectiveness of its AI-based tissue analysis platform ‘Lunit SCOPE’ that accurately predicts cancer patients’ response to immunotherapy.

The highlight of Lunit at ESMO (Free ESMO Whitepaper) 2021 is its announcement that Lunit SCOPE IO—one of Lunit SCOPE product lines—has been applied to a phase 1 clinical trial of a new drug for the first time. In a joint study with Y Biologics, a South Korean clinical-stage antibody biotech company, Lunit SCOPE IO accurately predicted immunotherapy response of all the patients who participated in the study.

"From 2019, Lunit has proven that response to immunotherapy varies depending on the spatial distribution of immune cells in cancer tissue, which has been the foundation for the AI platform ‘Lunit SCOPE IO’," said Chan-Young Ock, Chief Medical Officer of Lunit. "This study is the first case where Lunit SCOPE IO was applied to actual drug development clinical trials, and it is a meaningful study that demonstrated high potential for AI-powered biomarkers."

Lunit presented another study using Lunit SCOPE IO, validating the correlation between spatial information of tumor-infiltrating lymphocytes(TIL) and prognosis of colorectal cancer. The team analyzed 461 colorectal cancer data among TCGA data and showed that high TIL density in relation to tumor cells may improve prognostic power.

The company’s other major study was on Lunit SCOPE PD-L1, an AI-powered PD-L1 tumor proportion score(TPS) analyzer developed by Lunit. According to the study, assistance with Lunit SCOPE PD-L1 substantially improved pathologists’ consensus and found more patients who were eligible for immunotherapy.

"Although PD-L1 expression is the standard biomarker for advanced non-small cell lung cancer, manual evaluation of PD-L1 TPS by pathologists has practical limitations of interobserver bias and intensive labor," said Kyunghyun Paeng, Chief Product Officer of Lunit. "This study aimed to explore whether the AI-powered TPS analyzer could reduce the interobserver variation and increase the accuracy of analysis."

Three pathologists evaluated the PD-L1 TPS of 479 NSCLC data. Comparing the results of the analysis, the discordant rate in the subgroups of TPS <1% decreased from 32% to 10% when assisted with Lunit AI. Furthermore, 23 out of 81 were found to be eligible for immunotherapy even though they were evaluated to be TPS <1% by pathologists, meaning an additional 30% of patients could be treated with immunotherapy, who would otherwise have not been recommended for immunotherapy.

"We are now in the process of proving and creating the direction we want to achieve in the field of cancer treatment," said Brandon Suh, CEO of Lunit. "This year’s ESMO (Free ESMO Whitepaper) is particularly meaningful as one of our Lunit SCOPE products was used in a clinical trial for the first time and showed its predictable value. Our validation of AI-powered biomarkers for immunotherapy will be applied to many other drugs and larger clinical studies in the near future. In light of these positive results, Lunit SCOPE will be commercially made available by the end of this year."

Lunit Abstract Information at ESMO (Free ESMO Whitepaper) 2021

Virtual Meeting: E-Posters
September 16 – 21, 2021

Abstract 977P

Title: Interim results of phase I dose escalation study of YBL-006: A novel anti-PD-1 monoclonal antibody in advanced solid tumors

Abstract 398P

Title: AI-powered whole-slide image analysis of tumor-infiltrating lymphocytes for prediction of prognosis in colorectal cancer

Abstract 1805P

Title: Assistance with an artificial intelligence-powered PD-L1 analyzer reduces interobserver variation in pathologic reading of tumor proportion score in non-small cell lung cancer

Tyra Announces Closing of Initial Public Offering and Full Exercise of Underwriters’ Option to Purchase Additional Shares

On September 17, 2021 Tyra Biosciences, Inc. (Nasdaq: TYRA), a precision oncology company focused on developing purpose-built therapies to overcome tumor resistance and improve outcomes for patients with cancer, reported the closing of its initial public offering of 12,420,000 shares of common stock, which includes the exercise in full by the underwriters of their option to purchase 1,620,000 additional shares, at an initial public offering price of $16.00 per share (Press release, Tyra Biosciences, SEP 17, 2021, View Source [SID1234587909]). The aggregate gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Tyra, were $198,720,000 million. Tyra’s common stock is listed on the Nasdaq Global Select Market under the ticker symbol "TYRA."

BofA Securities, Jefferies and Cowen acted as joint book-running managers for the offering.

Registration statements relating to the offering have been filed with the Securities and Exchange Commission (SEC) and became effective on September 14, 2021. A prospectus relating to and describing the terms of the offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov. The offering was made only by means of a prospectus. Copies of the final prospectus may be obtained from BofA Securities, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, North Carolina 28255-0001, Attention: Prospectus Department, or by email at [email protected]; from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by email at [email protected] or by telephone at 877-821-7388; or from Cowen and Company, LLC, c/o Broadridge Financial Solutions, Attention: Prospectus Department, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (833) 297-2926, or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any offer or sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

Innovent Releases Interim Analysis Results of Sintilimab in Combination with Chemotherapy for the First-Line Treatment of Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma in the Phase 3 ORIENT-16 Study at ESMO Congress 2021

On September 17, 2021 Innovent Biologics, Inc. ("Innovent", HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, reported the interim analysis results of the Phase 3 ORIENT-16 study evaluating sintilimab in combination with chemotherapy compared to chemotherapy alone for the first-line treatment of advanced or metastatic gastric or gastroesophageal junction adenocarcinoma in an oral presentation at the ESMO (Free ESMO Whitepaper) (European Society for Medical Oncology) Congress 2021 (Abstract # LBA53) (Press release, Innovent Biologics, SEP 17, 2021, View Source [SID1234587908]).

As of the June 20, 2021 data cutoff date for the interim analysis, 650 patients have been enrolled. Sintilimab in combination with chemotherapy (oxaliplatin and capecitabine) demonstrated superior overall survival (OS) compared to placebo plus chemotherapy, with a 34.0% reduction in the risk of death (HR 0.660; 95%CI, 0.505-0.864; p=0.0023) and a 5.5-month improvement in median OS (18.4 months vs. 12.9 months) in patients with CPS ≥5, and 23.4% reduction in the risk of death and a 2.9-month improvement in mOS (15.2 months vs. 12.3 months) in all randomized patients (the ITT population). The OS benefits were consistent in all prespecified subgroup analyses. The safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified for the combination of sintilimab and chemotherapy.

The principal investigator of the ORIENT-16 study, Prof. Jianming Xu from the Fifth Medical Center of People’s Liberation Army General Hospital, stated, "ORIENT-16 is the first Phase 3 clinical trial in China to demonstrate an anti-PD-1 antibody in combination with chemotherapy significantly prolonged overall survival in the first-line treatment of advanced gastric cancer. Gastric cancer is one of the most common malignant tumor types globally and nearly half of all cases are diagnosed in China. The prognosis of advanced gastric cancer is very poor. The results of the ORIENT-16 study have the potential to bring a new treatment option to people with gastric cancer."

Dr. Zhou Hui, Senior Vice President of Innovent, stated, "While immunotherapy has greatly changed the treatment paradigm for many malignancies, it has not yet in gastric cancer. The treatment options for advanced gastric cancer are very limited and the ORIENT-16 study aimed to help address this unmet medical need. These results are very encouraging and confirmed the clinical value of sintilimab plus chemotherapy in the first-line treatment of advanced gastric cancer. We are grateful for all the contributions made by every investigator and patient in this study, and we hope that sintilimab can become a new treatment option for people with gastric cancer. Innovent planned to file a supplemental new drug application to the National Medical Products Administration (NMPA) in China based on the results of interim analysis. Up until now, sintilimab has demonstrated improved survival in the first-line treatment of five major types of cancer – nonsquamous non-small cell lung cancer, squamous non-small cell lung cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer."

About the ORIENT-16 Study

ORIENT-16 is a randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab in combination with chemotherapy (oxaliplatin and capecitabine), compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (ClinicalTrials.gov, NCT03745170). The primary endpoint was overall survival, in all randomized and in PD-L1 positive patients.

About Gastric Cancer

Gastric cancer is one of the most common malignant tumor types worldwide. According to GLOBOCAN estimates, there were approximately one million new cases and 769,000 new deaths of gastric cancer in 2020, making it the fifth most common cancer and third leading cause of cancer death globally. About half of all gastric cancer cases occurred in East Asia, mainly in China. The first-line treatment of advanced gastric cancer remains limited. Currently, the five-year survival rate of advanced or metastatic gastric cancer ranges from 5 to 20 percent, and the median overall survival is approximately one year.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for four indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has a regulatory submission under review in China for sintilimab for the second-line treatment of squamous non-small cell lung cancer.

Innovent also has three clinical studies of sintilimab that have met their primary endpoints:

In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
In combination with oxaliplatin and capecitabine for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma
The second-line treatment of esophageal squamous cell carcinoma
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

Innovent Releases Interim Analysis Results of Sintilimab plus Chemotherapy for the First-Line Treatment of Esophageal Squamous Cell Carcinoma in the Phase 3 ORIENT-15 Study at ESMO Congress 2021

On September 17, 2021 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, reported that the interim analysis results of the Phase 3 ORIENT-15 study evaluating sintilimab in combination with chemotherapy for the first-line treatment of esophageal squamous cell carcinoma (ESCC) were released today in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 (Abstract # LBA52) (Press release, Innovent Biologics, SEP 17, 2021, View Source [SID1234587907]).

All endpoints of ORIENT-15 were met at the interim analysis. As of the April 9, 2021 data cutoff, 659 patients were randomly assigned and received treatment. Sintilimab plus chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil [5-FU]) resulted in a superior median overall survival (mOS) over placebo plus chemotherapy in all randomized patients (the ITT population) (16.7 vs 12.5 months, respectively; HR 0.628; P<0.0001) and in PD-L1 positive patients (defined as combined positive score [CPS] ≥10) (17.2 vs 13.6 months, respectively; HR 0.638; P=0.0018). Sintilimab plus chemotherapy significantly improved median progression-free survival (mPFS) in all randomized patients (7.2 vs 5.7 months, respectively; HR 0.558; P<0.0001) and in PD-L1 positive patients (8.3 vs 6.4 months, respectively; HR 0.580; P<0.0001). The safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified for the combination of sintilimab and chemotherapy.

The principal investigator of the ORIENT-15 study, Prof. Shen Lin from Peking University Cancer Hospital and Institute, stated, "More than half of new and fatal cases of esophageal cancer in the world occur in China every year. Esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer in China, and squamous cell carcinoma is the predominant histologic type. The treatment options for locally advanced or metastatic ESCC are limited and represent a significant unmet clinical need. The ORIENT-15 results suggest that sintilimab in combination with chemotherapy may represent a first-line treatment option for patients with advanced or metastatic ESCC."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "We thank the investigators and study team for their joint effort and, most importantly, we would like to express our sincere gratitude to all the patients who participated in the ORIENT-15 study. We have submitted an application to the National Medical Products Administration (NMPA) of China in early September based on these results, and hope that sintilimab plus chemotherapy can become a first-line treatment option for ESCC patients in the near future ."

About the ORIENT-15 Study

ORIENT-15 is a global randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil [5-FU]), compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ClinicalTrials.gov, NCT03748134). At the time of interim analysis, a total of 659 eligible patients (of the planned 676 estimated participants) were enrolled and randomly assigned into the experimental group or control group in a 1:1 ratio. The primary endpoints were overall survival (OS) in all randomized patients and OS in PD-L1 positive (defined as CPS ≥10) patients.

About Esophageal Squamous Cell Carcinoma (ESCC)

Esophageal cancer (EC) is one of the most common malignant tumors worldwide that begins in the inner layer (mucosa) of the esophagus, which connects the throat to the stomach. Based on GLOBOCAN 2020 estimates, approximately 600,000 new cases of esophageal cancer are diagnosed and approximately 540,000 deaths result from the disease worldwide each year. Esophageal cancer is the seventh most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwide. More than half of new and fatal cases of esophageal cancer in the world occur in China. In China, it is estimated there were approximately 320,000 new cases of esophageal cancer diagnosed and approximately 300,000 deaths resulting from the disease in 2020. Esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer in China, where it has a five-year survival rate of only 30%. In the US, it is estimated there were approximately 18,000 new cases of esophageal cancer diagnosed and approximately 16,000 deaths resulting from the disease in 2020. The five-year survival rate of esophageal cancer is only 20% in the US.

The two main types of esophageal cancer are squamous cell carcinoma (SCC) and adenocarcinoma. In China, SCC is the predominant histologic type, accounting for more than 90% of all esophageal cancer. In western countries, SCC is approximately 25% of all esophageal cancer. In the past first-line standard systemic therapy was chemotherapy based on platinum drugs for unresectable locally advanced, recurrent or metastatic ESCC. Pembrolizumab has been approved as first-line treatment in combination with chemotherapy.