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Exact Sciences to Present Late-Breaking Data from ASCEND-2 Study Validating Its Investigational Multi-Cancer Early Detection Test at AACR Annual Meeting 2024

On April 8, 2024 Exact Sciences Corp. (NASDAQ: EXAS), a leading provider of cancer screening and diagnostic tests, reported that it will present late-breaking data from the first analysis of the ASCEND-2 study demonstrating the compelling performance of its investigational multi-biomarker class, multi-cancer early detection (MCED) blood test (Press release, Exact Sciences, APR 8, 2024, View Source [SID1234641865]). These results validate the sensitivity and specificity of the company’s multi-biomarker class approach across a broad range of cancer types, including the most aggressive cancers and cancers with no current standard of care for screening. ASCEND-2 is a large, multi-center, prospective, case-control study of over 11,000 clinically characterized participants from a racially, ethnically, and geographically diverse cohort representative of the U.S. population. These data will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, April 5-10 in San Diego, California.1

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"Cancer is the second-leading cause of death in the U.S., and while early detection is associated with longer survival, two-thirds of deaths are caused by cancers that lack standard screening tests. MCED tests have the potential to revolutionize cancer screening by enabling us to spot more cancers and intervene earlier," said Tom Beer, MD, Chief Medical Officer, Multi-Cancer Early Detection, Exact Sciences.2-4 "This analysis from ASCEND-2 confirms that our multi-biomarker class approach to MCED test design may deliver benefits beyond what is currently achievable. The sensitivity and specificity achieved in the detection of the most aggressive cancers and those cancers with no current standard of care provide the confidence to move forward to a real-world evidence study."

Exact Sciences will also present new outcomes data from DETECT-A, the first large prospective study of an earlier multi-biomarker class MCED test that enrolled more than 10,000 participants with more than four years of follow-up.5

The abstracts featured at AACR (Free AACR Whitepaper) 2024 are as follows:

Title: Performance of a multi-analyte, multi-cancer early detection (MCED) blood test in a prospectively collected cohort
Presenter: Diehl, F
Session: Monday, April 8, 9:00 a.m. – 12:30 p.m. PDT (Session LBPO.CL01)
Poster number: LB100/11
Location: Section 51
Key findings: First analysis of the refined multi-biomarker class MCED test achieved an overall sensitivity of 50.9% with 98.5% specificity and 56.8% sensitivity when breast and prostate cancer were excluded from the analysis. Sensitivity was 54.8% for cancers without standard-of-care screening for average-risk populations and 63.7% in the most aggressive cancers with the shortest 5-year survival rate (pancreas, esophagus, liver, lung and bronchus, stomach, and ovary).

Title: Case report: DETECT-A participants with pre-malignant conditions
Presenter: Rego, SP
Session: Monday, April 8, 9:00 a.m. – 12:30 p.m. PDT (Session PO.CL01.16)
Poster number: 2449/14
Location: Section 41
Key findings: Results showed that in the rare instance when MCED testing detected pre-cancerous conditions in the DETECT-A study, surgical interventions prevented cancer development, and all patients were cancer-free at follow-up.

About the ASCEND-2 study

The ASCEND-2 (Ascertaining Serial Cancer patients to Enable New Diagnostic 2) study is a large, multi-center, prospective, case-control study of clinically characterized participants. Key goals of the study are to develop the algorithm and identify the biomarkers to inform the final design of the Cancerguard test, Exact Sciences’ investigational, multi-biomarker class blood-based MCED test. ASCEND-2 has enrolled over 11,000 participants across 151 sites within the U.S. and Europe. The study population includes male and female subjects 50 years and over with known cancer, suspicion of cancer, and controls without cancer. ASCEND-2 selected cancer types in an incidence-targeted manner, including rare and common cancers and evenly distributed stages. By enrolling racially, ethnically, and geographically diverse participants, the study enables MCED test development with a widely representative cohort.

About the DETECT-A study

The DETECT-A (Detecting cancers Early Through Elective mutation-based blood Collection and Testing) study was the first-ever large, prospective, interventional study to use a blood test to detect multiple types of cancer in a real-world setting. The DETECT-A study enrolled more than 10,000 women with no history of cancer to determine if a blood test in combination with standard-of-care screenings could detect cancers before signs and symptoms appeared. The CancerSEEK test, the MCED test studied in DETECT-A, was the forerunner to the Cancerguard test, the MCED test currently in development at Exact Sciences.

About the Cancerguard test

The Cancerguard test, currently in development, is designed to detect multiple cancers in their earliest stages from a single blood draw. Building upon decades of research, Exact Sciences intends to harness the additive sensitivity of multiple biomarker classes to detect more cancers in earlier stages. The Cancerguard test will utilize a streamlined and standardized imaging-based diagnostic pathway, which may result in fewer follow-up procedures. The test is being developed to provide high specificity to help minimize false positives while detecting multiple cancers, including those with the biggest toll on human health. The Cancerguard test is currently under development. These features describe current development goals. The Cancerguard test has not been cleared or approved by the U.S. Food and Drug Administration or any other national regulatory authority. To learn more, visit View Source

Elevation Oncology Presents Preclinical Proof-of-Concept Data for HER3-ADC Program at AACR Annual Meeting 2024

On April 8, 2024 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported new preclinical data demonstrating proof-of-concept for its differentiated HER3-ADC program (Press release, Elevation Oncology, APR 8, 2024, View Source;utm_medium=rss&utm_campaign=elevation-oncology-presents-preclinical-proof-of-concept-data-for-her3-adc-program-at-aacr-annual-meeting-2024 [SID1234641864]). The data will be presented in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, being held April 5-10 in San Diego, California.

"We are pleased to share the first preclinical proof-of-concept data for our HER3-ADC program, reinforcing our commitment to advancing a portfolio of differentiated ADC-based therapies that may deliver better outcomes for patients," said David Dornan, Ph.D., Chief Scientific Officer of Elevation Oncology. "With our HER3-ADC program, we set out to design a differentiated ADC which selectively binds to HER3 and is internalized to potentially attack HER3-expressing cancerous cells while minimizing systemic exposure. Preclinical data with our proof-of-concept HER3-ADC shows HER3-dependent cell killing and robust anti-tumor activity in vivo where HER3 is expressed at high levels. We look forward to nominating a development candidate from our HER3 program later this year and, subsequently, advancing our program closer to the clinic."

HER3 is a clinically validated oncology and antibody-drug conjugate (ADC) target, which is overexpressed in a range of solid tumors, including breast cancer, EGFR-mutant non-small cell lung cancer and pancreatic cancer, and is often associated with poor clinical outcomes. Elevation Oncology’s HER3-ADC program conjugated seribantumab, its anti-HER3 monoclonal antibody, with a cleavable valine-citrulline linker and monomethyl auristatin E (MMAE) payload to yield HER3-ADC1, a proof-of-concept molecule with an average drug-antibody ratio (DAR) of 4.

In a poster titled, "Therapeutic potential of a HER3 antibody-drug conjugate for the treatment of HER3-expressing cancers," Elevation Oncology scientists presented in vitro and in vivo data of a seribantumab-based ADC for patients with HER3-expressing cancers. The data showed:

HER3-ADC1 binding to cancer cells, endocytosis, MMAE release and inhibition of proliferation were dependent on HER3 expression.
In cytotoxicity assays, HER3-ADC1 displayed HER3-dependent cell killing and outperformed a benchmark HER3-ADC with a deruxtecan payload, which is currently in clinical development.
In a patient derived xenograft (PDX) model of pancreatic cancer with high HER3 expression, HER3-ADC1 induced tumor regression, whereas an isotype-MMAE control and a benchmark HER3-ADC with a deruxtecan payload had only a modest effect.
The poster presentation is now available in the "Publications" section of Elevation Oncology’s website: View Source

CytomX Therapeutics Announces First Patient Dosed with CX-2051, a Conditionally Activated EpCAM-Directed ADC, in a Phase 1 Study in Patients with Advanced Solid Tumors

On April 8, 2024 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated, localized biologics, reported the first patient has been dosed in a Phase 1 dose escalation study (NCT06265688) of CX-2051 in patients with advanced solid tumors (Press release, CytomX Therapeutics, APR 8, 2024, View Source [SID1234641863]). CX-2051 is a masked PROBODY antibody drug conjugate (ADC) directed toward epithelial cell adhesion molecule (EpCAM), a cell-surface target that is highly expressed across many cancer types including colorectal, gastric, endometrial, and ovarian cancers. The cytotoxic payload utilized in CX-2051 is a derivative of camptothecin, a topoisomerase-1 inhibitor, a class of drug that has shown potent clinical anti-cancer activity and demonstrated significant clinical benefit as an approved ADC in multiple cancers. The CX-2051 Phase 1 dose escalation is designed to efficiently test the safety and preliminary anti-tumor activity of CX-2051, to provide initial clinical proof of concept to inform a potential decision to move into dose expansions in 2025.

"EpCAM is a high potential ADC target present at high levels on many solid cancers. CX-2051 has been optimized using our tailored masking strategies and possesses a potent cytotoxic payload ideally suited to specific EpCAM positive tumor types, including colorectal cancer. The successful initiation of the Phase 1 dose escalation study for CX-2051 is an important clinical milestone for CytomX as we continue to advance our multi-modality PROBODY therapeutic pipeline to address areas of significant unmet medical need," said Wayne Chu, M.D., chief medical officer of CytomX Therapeutics.

Corcept Completes Enrollment in Pivotal Phase 3 ROSELLA Trial of Relacorilant in Patients With Platinum-Resistant Ovarian Cancer

On April 8, 2024 Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic and neurologic disorders by modulating the effects of the hormone cortisol, reported completion of enrollment in ROSELLA, a pivotal Phase 3 trial of its proprietary selective cortisol modulator relacorilant combined with nab-paclitaxel in patients with recurrent, platinum-resistant ovarian cancer (Press release, Corcept Therapeutics, APR 8, 2024, https://ir.corcept.com/news-releases/news-release-details/corcept-completes-enrollment-pivotal-phase-3-rosella-trial [SID1234641862]).

"Fully enrolling ROSELLA takes us a big step closer to addressing the unmet medical need of women with platinum-resistant ovarian cancer," said Bill Guyer, PharmD, Corcept’s Chief Development Officer. "Relacorilant has the potential to become the standard of care for patients with this devastating disease. We expect progression-free survival data, ROSELLA’s primary endpoint, by the end of this year."

The ROSELLA trial has the same design as Corcept’s positive Phase 2 study, in which patients who received relacorilant intermittently – the day before, the day of and the day after they received nab-paclitaxel – exhibited improvements in progression-free survival, duration of response and overall survival compared to patients who received nab-paclitaxel alone, without an increased side effect burden. These results were published in the Journal of Clinical Oncology in June 2023.

The ROSELLA trial enrolled 381 women at sites in the United States, Europe, South Korea, Brazil, Argentina, Canada and Australia. Patients were randomized 1:1 to receive either relacorilant dosed intermittently with nab-paclitaxel or nab-paclitaxel monotherapy. ROSELLA’s primary endpoint is progression-free survival. Overall survival is a key secondary endpoint.

About Platinum-Resistant Ovarian Cancer
Ovarian cancer is the fifth most common cause of cancer death in women. Patients whose disease returns less than six months after receiving platinum-containing therapy have "platinum-resistant" disease. There are few treatment options and median overall survival following recurrence is 12 months or less with single-agent chemotherapy.1 In the United States, approximately 20,000 women with platinum-resistant disease are candidates to start a new therapy each year.

About Relacorilant
Relacorilant is a selective cortisol modulator that binds to the glucocorticoid receptor (GR), but does not bind to the body’s other hormone receptors. Corcept is studying relacorilant in a variety of serious disorders, including ovarian, adrenal and prostate cancer and Cushing’s syndrome. Relacorilant is proprietary to Corcept and is protected by composition of matter, method of use and other patents.

Coherus Presents Preclinical Data for CHS-1000, a Novel Anti-ILT4 Antibody, at the 2024 AACR Annual Meeting

On April 8, 2024 Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), reported preclinical data for its immuno-oncology pipeline candidate, CHS-1000, a novel ILT4 monoclonal antibody, at the 2024 AACR (Free AACR Whitepaper) Annual Meeting being held in San Diego, California (Press release, Coherus Biosciences, APR 8, 2024, View Source [SID1234641861]). Data presented show CHS-1000 is a potent monoclonal antibody that binds selectively to human ILT4 (also known as LILRB2) with high affinity, efficiently blocking interaction with its ligands and reversing immunosuppressive functions, leading to activation of human dendritic cells and T cells and promoting polarization of macrophages to an inflammatory M1 phenotype.

"Myeloid cell-mediated immunosuppression in the tumor microenvironment is a major contributor to tumor immune invasion and PD-1 resistance. The data presented in this poster demonstrate the potential for CHS-1000 to reverse myeloid suppression and activate an inflammatory immune response. Reprogramming myeloid cells in the tumor microenvironment holds promise as a new immuno-therapy approach with the aim to overcome resistance to I-O therapy and potentially provide benefit to more cancer patients," said Theresa LaVallee, Ph.D., Chief Development Officer at Coherus. "CHS-1000 is our first internally discovered development candidate, and we are excited to be filing the IND this quarter. We plan to advance CHS-1000 into the clinic both as a single agent and in combination with LOQTORZI."

These data will be presented today in a poster session, and the poster will be available for download at the time of the presentation:

Abstract: 1364/15
Title: Characterization of CHS-1000, an Fc-modified anti-ILT4 monoclonal antibody for reprogramming suppressive myeloid cells in solid tumors
Presenting author: Narendiran Rajasekaran, Ph.D.
Session PO.IM01.02 – Immune Checkpoints and Inhibitory Molecules 1
Date and Time: Monday, April 8, 2024, 9:00 a.m. – 12:30 p.m. Pacific Daylight Time

Poster data are summarized as follows:

CHS-1000 binds specifically and selectively to human ILT4 (LILRB2) with high affinity and showed no cross-reactivity to other LILRB family members.
CHS-1000 efficiently blocks the interaction of ILT4 with its ligands, HLA-A and HLA-G, and reverses ILT4-mediated immunosuppressive functions, leading to activation of M1 macrophages, dendritic cells, and T cells and increases in pro-inflammatory cytokine secretion in in vitro assays.
CHS-1000 is Fc silent and lacks effector function activity in in vitro assays consistent with the engineered modification of the Fc region of the antibody. It also has IgG1‑like PK parameters in human FcRn transgenic mice.
ILT4 and CD163, a marker of suppressive (M2) macrophages, are highly expressed in a broad range of solid tumors.

About CHS-1000

Discovered and developed by Coherus, CHS-1000 is a novel humanized Fc-modified IgG1 monoclonal antibody specifically targeting ILT4 (LILRB2). CHS-1000 is designed to overcome myeloid cell-mediated immunosuppression and resistance in the tumor microenvironment. In preclinical studies, CHS-1000 promotes repolarization of suppressive M2 macrophages to a pro-inflammatory M1 phenotype and enhances activation of dendritic cells and T cells in vitro. Coherus plans to file an investigational new drug (IND) application in Q2 2024 and begin clinical studies later this year.