On December 1, 2021 Labcorp (NYSE: LH), a leading global life sciences company, and ConcertAI, LLC (ConcertAI), a leader in enterprise artificial intelligence (AI) and real-world data (RWD) solutions for life science companies and health care providers, reported a collaboration to optimize precision oncology research (Press release, LabCorp, DEC 1, 2021, View Source [SID1234596375]). The companies will work together to launch clinical studies in ways that minimize the burden on physician practices, drive faster patient recruitment, maximize patient retention and ensure equitable access to research as a care option.

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Through this collaboration, Labcorp will leverage ConcertAI’s suite of software-as-a-service (SaaS) offerings for clinical trial design, protocol optimization, site selection and study execution. These solutions, when paired with Labcorp’s expertise in clinical development services and diagnostic testing, will optimize oncology clinical trial design and execution using RWD and AI.

"With Labcorp, we are building an advanced network, AI technologies and SaaS solutions to further advance the industry’s goals for diversity and digital enablement in clinical development services, especially in oncology," said Jeff Elton, Ph.D., CEO of ConcertAI. "As a leading RWD and SaaS AI solutions company for evidence generation, ConcertAI is committed to advancing precision oncology in partnership with industry leaders."

ConcertAI’s offerings will allow Labcorp Drug Development to access data to make more informed decisions about oncology clinical trials. This analytical toolset drives actionable insights that will lead to a better understanding of patient profiles and treatment pathways, ultimately yielding quicker and more effective clinical trials.

Clinical trials also increasingly require analysis of potential trial sites to identify and select locations containing patients with specific characteristics. Using data to help understand the availability of patients across a sampling of oncology cancer centers helps bring health care within reach for all and ensures that the design of a trial contains a diverse set of participants to measure drug safety and effectiveness in broadly representative populations. ConcertAI and Labcorp have structured a long-term collaboration to leverage data and analytics to find solutions to these difficult problems.

"Oncology is highly complex, with hundreds of molecular targets and factors across solid tumors and hematological malignancies, so the need is great for diversity in cancer trials," said Prasanth Reddy, M.D., MPH, FACP, senior vice president and head of oncology at Labcorp. "Labcorp Drug Development, which supports more than 50% of all oncology clinical trials globally, combined with ConcertAI’s high-depth data and AI technologies, is a powerful combination to optimize trial design, improve patient access, and increase efficiency of oncology trials to bring new therapeutic options to patients who need them most."

Improved screening, along with new diagnostics and treatments in cancer have been significant contributors to recent reductions in deaths and other adverse outcomes. Health care providers and pharmaceutical companies require support to bring additional, innovative treatment options to market. Pairing ConcertAI’s RWD and AI expertise with Labcorp Drug Development’s established site relationships and patient-centric approach will provide customers with a differentiated offering, generating actionable insights and improved trial execution—ultimately yielding trials that are more cost effective, more inclusive and more likely to succeed.

On December 1, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that the Company has initiated a Phase 2, single arm, open-label study of trilaciclib in patients with early-stage triple negative breast cancer (TNBC) designed to further investigate the role of trilaciclib in modulating the anti-tumor immune response (Press release, G1 Therapeutics, DEC 1, 2021, View Source [SID1234596317]). Pathologic complete response endpoints are also being evaluated in this trial. Initial results of this study are expected in the second half of 2022.

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"Data from our Phase 2 TNBC trial of trilaciclib in combination with chemotherapy showed clinically meaningful and substantial improvements in overall survival as well as enhanced measures of immune system function compared to chemotherapy alone," said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. "Those preliminary data support the important role trilaciclib may play in treating cancer by enhancing T cell activation and favorably altering the tumor microenvironment. This Phase 2 clinical study will support trilaciclib’s mechanistic effects potentially responsible for enhanced anti-tumor immune responses in patients and generate important data that will help guide our future development decisions across additional tumor types and new treatment combinations."

Patient recruitment in this trial is now underway. Approximately 30 patients will be enrolled in this Phase 2 multicenter, open-label, single-arm, neoadjuvant study. Up to three tumor tissue samples will be collected for assessment. Tumor tissue will be obtained at baseline prior to study drug administration. Patients will receive a single dose of monotherapy trilaciclib, followed by a tumor biopsy approximately one week later. Following the biopsy, patients will enter the treatment phase in which trilaciclib will be administered on Day 1 of each cycle of anthracycline/cyclophosphamide for four cycles followed by trilaciclib administered on Day 1 of each weekly cycle of taxane chemotherapy for 12 cycles. Immune checkpoint inhibitor and/or carboplatin may be added to therapy at the discretion of the investigator. Three to five weeks after the last dose of chemotherapy, patients will proceed to surgery at which time a third tumor tissue sample will be collected if the patient has residual disease.

Study treatment will continue as per protocol to completion or early discontinuation of chemotherapy, until unacceptable toxicity, Investigator’s decision to withdraw the patient from study treatment, consent withdrawal, or the end of the study, whichever occurs first.

The primary objective is to evaluate the immune-based mechanism of action of trilaciclib after a single-dose as measured by the change in the ratio of CD8+ tumor-infiltrating lymphocytes (TILs) to regulatory T cell (Tregs) in the tumor microenvironment. Key secondary and exploratory endpoints include:

Assessment of pathologic complete response (pCR) rate at the time of definitive surgery.
Evaluation of the safety and tolerability of trilaciclib in combination with standard neoadjuvant systemic therapies.
Tumor mRNA analyses and immunohistochemistry and peripheral blood immune profiling following trilaciclib.
Identification of molecular and cellular biomarkers in tumor or blood samples that may be indicative of clinical response/resistance, pharmacodynamic activity, and/or the mechanism of action of trilaciclib and other systemic treatments.
About Triple Negative Breast Cancer (TNBC)
According to the American Cancer Society, nearly 300,000 new cases of invasive breast cancer are diagnosed annually in the U.S. Triple-negative breast cancer makes up approximately 15-20% of such diagnosed breast cancers. TNBC is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. Because mTNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. Instead, treating mTNBC typically involves chemotherapy, radiation, and surgery. TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. In general, survival rates tend to be lower with mTNBC compared to other forms of breast cancer, and mTNBC is also more likely than some other types of breast cancer to return after it has been treated, especially in the first few years after treatment. It also tends to be higher grade than other types of breast cancer.

On November 1, 2021 Exact Sciences Corp. (NASDAQ: EXAS) reported that data from the Rx for Positive Node, Endocrine Responsive Breast Cancer, or RxPONDER, trial were published in The New England Journal of Medicine (Press release, Exact Sciences, DEC 1, 2021, View Source [SID1234596335]).i The study, led by the independent SWOG Cancer Research Network and sponsored by the National Cancer Institute (NCI), successfully defined the benefit of chemotherapy in early-stage, node-positive breast cancer patients with Oncotype DX Breast Recurrence Score results of 0 to 25. Initial results from RxPONDER were reported at the 2020 San Antonio Breast Cancer Symposium (SABCS). The findings have now been confirmed in this peer-reviewed publication.

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RxPONDER results show that guiding treatment w/ Oncotype DX test can spare chemo use in majority of postmenopausal women
In the study, postmenopausal women with 1 to 3 positive nodes and Recurrence Score results of 0 to 25 showed no benefit from chemotherapy after a median of five years of follow-up, meaning they can potentially avoid negative side effects of the treatment. Importantly, no chemotherapy benefit was observed regardless of the number of affected nodes, tumor grade or size. In premenopausal women with 1 to 3 positive nodes, a statistically significant chemotherapy benefit was observed.

Approximately one-third of patients diagnosed with hormone receptor (HR)-positive, HER2-negative early breast cancer have a tumor that has spread to their lymph nodes. The vast majority of these patients currently receive chemotherapyii even though approximately 85% of them have Recurrence Score results of 0 to 25.iii In addition, approximately two out of three early-stage breast cancer patients are postmenopausal.iv

"Our goal with RxPONDER was to better understand when to use adjuvant chemotherapy to enable personalized treatment instead of a one-size-fits-all approach," said study lead author Kevin Kalinsky, M.D., a long-time SWOG investigator and director of the Glenn Family Breast Center at the Winship Cancer Institute of Emory University. "These practice-changing results definitively show that postmenopausal women with this common form of breast cancer can be spared unnecessary chemotherapy and receive only hormone therapy, potentially saving tens of thousands of women the time, expense and harmful side effects that can be associated with chemotherapy. For the women diagnosed with breast cancer prior to menopause who may benefit from chemotherapy, the data help individualize the discussion of risk and benefit of chemotherapy."

Based on the RxPONDER results, the National Comprehensive Cancer Network (NCCN)v updated its guidelines for breast cancer and recognized the Oncotype DX Breast Recurrence Score test as the only test that can be used for prediction of chemotherapy benefit in early-stage breast cancer patients with 1 to 3 positive axillary lymph nodes, including micrometastases.vi The Oncotype DX test is now the only test classified as "preferred" with the highest level of evidence for node-negative and postmenopausal node-positive (1 to 3 positive nodes) patients. In addition, NCCN recommends considering the test to assess prognosis in premenopausal node-positive patients who are candidates for chemotherapy.

"The RxPONDER results, together with the foundational TAILORx resultsvii in node-negative, early-stage breast cancer, further elevate the test to a standard of care, supporting its inclusion in guidelines as well as its reimbursement and adoption on a global scale," said Rick Baehner, M.D., chief medical officer of Precision Oncology at Exact Sciences. "Now with the RxPONDER results, many more women worldwide may be able to receive hormone therapy alone, avoiding the negative side effects of chemotherapy without increasing the risk of cancer returning."

One of the largest clinical trials in node-positive, HR-positive, HER2-negative early breast cancer, RxPONDER enrolled more than 5,000 women with up to three positive nodes. The prospective, randomized Phase III study was conducted at 632 sites in nine countries – the United States, Canada, Mexico, Colombia, Ireland, France, Spain, South Korea and Saudi Arabia. Women with a Recurrence Score result of 0 to 25 were randomized to treatment with hormone therapy alone or chemotherapy followed by hormone therapy. Randomized patients were stratified based on their Recurrence Score result, menopausal status and type of lymph node surgery. Further analyses and additional patient follow up are planned by the SWOG investigators.

About the Oncotype DX and Oncotype MAP Portfolio of Tests
The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. In breast cancer, the Oncotype DX Breast Recurrence Score test is the only test that has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in invasive breast cancer. Additionally, the Oncotype DX Breast DCIS Score test predicts the likelihood of recurrence in a pre-invasive form of breast cancer called DCIS. For patients with advanced and metastatic cancer, the company offers the Oncotype MAP Pan-Cancer Tissue test, a rapid, comprehensive tumor profiling panel, which provides results in three to five business daysviii and allows physicians to understand a patient’s tumor profile and recommend actionable targeted therapies or clinical trials. With more than 1 million patients tested in more than 90 countries, the Oncotype DX tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about the Oncotype DX and Oncotype MAP tests, visit www.OncotypeIQ.com/

On December 1, 2021 LintonPharm Co., Ltd., a China-based clinical stage biopharmaceutical company focused on the development of T cell engaging bispecific antibodies for cancer immunotherapy, reported that the first patient has been dosed in the Company’s Phase 1/2 clinical trial program for catumaxomab (clinicaltrials.gov: NCT04799847), a monoclonal bispecific antibody being studied for the treatment of Non-Muscle-Invasive Bladder Cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG) (Press release, Lintonpharm, DEC 1, 2021, View Source [SID1234596354]).

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"The initiation of our Phase 1 trial of catumaxomab for the treatment of NMIBC is an important step in our clinical program evaluating catumaxomab as targeted therapy in a broad range of cancers", said Robert Li, PH.D., DABT, Co-founder and CEO of LintonPharm. "Patients with NMIBC BCG failure need new therapies due to the limitations of current treatments which bring poor prognosis, such as high rates of tumor recurrence, bladder dysfunction and lifelong intervention. Based on encouraging pre-clinical data and clinical experience with patients who’ve received catumaxomab in the past through the compassionate use program, we are hopeful that catumaxomab will be a very promising immunotherapy candidate for patients with NMIBC BCG failure."

A recent publication indicated clinical benefits of catumaxomab as compassionate use in patients with EpCAM-positive recurrent NMIBC. It is noted that catumaxomab was well tolerated and presented promising performance in tumor control [1]. Based on the data and the developmental potential, catumaxomab could provide a feasible, safe, and efficacious therapy for NMIBC patients, if approved.

Bladder cancer is the 10th most commonly diagnosed cancer worldwide, with approximately 573,000 new cases in 2020 and roughly 75 percent are diagnosed as NMIBC [2][3]. Currently, the mainstay treatments of NMIBC include transurethral resection, chemotherapy and intravesical BCG [3].

About Catumaxomab

Catumaxomab was approved by the European Medicines Agency in 2009 for the treatment of malignant ascites. This bispecific antibody binds to a transmembrane glycoprotein on the tumor cell–the epithelial cell adhesion molecule (EpCAM)–and CD3 on the T cell, and also recruits immune accessory cells through FcγR binding. Catumaxomab destroys tumor cells by engaging T cell and accessory cell mediated cytotoxicity and has the potential to induce long-term vaccinal effects which has been verified in animal models.

Recently, catumaxomab was authorized by regulatory authorities in China, Taiwan (China) and South Korea to conduct a global Phase 3 clinical trial for treating patients with advanced gastric cancer (clinicaltrials.gov: NCT04222114).

On December 1, 2021 Zetagen Therapeutics, a private, clinical-stage, biopharmaceutical company dedicated to driving breakthrough innovation in the treatment of metastatic bone cancers and osteologic interventions, reported it has received Breakthrough Device designation from the Centers for Devices and Radiological Health (CDRH) of the U.S. Food and Drug Administration (FDA) for its ZetaMet technology (Press release, Zetagen Therapeutics, DEC 1, 2021, View Source [SID1234596376]). Previously known as ZetaFuse, ZetaMet is a synthetic, small-molecule, inductive biologic technology being developed to target and resolve metastatic bone lesions while inhibiting future tumor growth and regenerating bone.

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"We are pleased to receive this important designation from the Agency and look forward to partnering with them," said Joe C. Loy, CEO of Zetagen Therapeutics. "Our researchers have discovered an entirely new pathway for an established molecule which, if proven successful in human clinical trials, could create a new treatment paradigm for the hundreds of thousands of patients living with cancers that involve metastatic bone lesions."

ZetaMet works through a mechanism of action (MOA) which is a novel and patented molecular pathway. The small molecule, precisely-dosed, delivered to the affected area through a proprietary drug-eluting carrier, stimulates stem cells, activating cells to grow healthy bone known as "osteoblasts", and inhibits cells associated with bone degradation called "osteoclasts". The combination technology has, thus far, in preclinical studies, demonstrated its ability to resolve existing metastatic bone lesions, inhibit pain and stimulate targeted bone regeneration.

Bone metastases are common among cancer patients and occur when cells from the primary cancerous tumor relocate to the bone. When these cancers relocate, they can cause changes to the bone, damaging it in a process called osteolysis. Osteolysis can cause small holes within the bone, weakening it and increasing the risk of breakage. These holes are called "lytic lesions." Among cancers which metastasize to bone, Breast and Prostate are most prevalent, amounting to approximately 70-percent of cases.1

ZetaMet has successfully passed its preclinical trials and is being prepared for its first human clinical trial in early 2022.