On September 16, 2024 Exact Sciences Corp. (NASDAQ: EXAS), a leading provider of cancer screening and diagnostic tests, reported performance data for its blood-based colorectal cancer (CRC) screening test (Press release, Exact Sciences, SEP 16, 2024, View Source [SID1234646650]). Results show sensitivities of 88.3% for CRC and 31.2% for advanced precancerous lesions at specificity of 90.1% for negative samples confirmed by colonoscopy. Results were presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in an oral presentation titled, "Organ-specific performance of a multi-analyte, multi-cancer early detection (MCED) blood test in a prospectively-collected cohort."

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"The Exact Sciences team is constantly innovating to help close the screening gap," said Kevin Conroy, chairman and CEO, Exact Sciences. "The insights that led to this innovation reflect our understanding of the biology of cancer and the power of our scientific capabilities. We took a unique scientific approach to developing this test by combining a novel panel of markers. This led to data that improve upon what we previously thought was possible with a blood-based colorectal cancer screening test."

To optimize the final test algorithm, Exact Sciences designed a study to simulate the screening population in the United States and better predict real-world, prospective performance of a novel test. The study consisted of more than 3,000 blood samples, including approximately 2,900 blinded, prospectively collected samples from the pivotal BLUE-C study. This analysis was prespecified with the U.S. Food and Drug Administration (FDA) and the samples will be excluded from the final clinical validation. The study also included more than 90 advanced precancerous lesions, the majority of which were prospectively collected, and 60 case-collected colorectal cancer samples. In the pivotal BLUE-C study results, performance degradation is expected for advanced precancerous lesion sensitivity and overall CRC sensitivity.

Results of this study show the potential of a novel, highly discriminate blood-based panel of methylated DNA markers and an impactful, new marker class to detect advanced precancerous lesions and cancers at an attractive cost profile. The company will implement the innovative marker class on a new testing platform and complete additional analytical studies to support an FDA submission.

"A blood-based colorectal cancer screening test that can detect advanced precancerous lesions at a level comparable to the FIT test would be a breakthrough in this field," said Paul Limburg, MD, MPH, AGAF, chief medical officer for Screening, Exact Sciences. "Results from this large, well-designed study show progress toward that goal and move us one step closer toward providing average-risk patients with another non-invasive screening option."

BLUE-C results for Exact Sciences’ blood-based CRC screening test are now expected in the first half of 2025. Exact Sciences plans to use these results to support an FDA submission and approval and to make the blood-based CRC screening test available broadly. If approved, the blood-based CRC screening test could provide another testing option for 60 million unscreened people 1 in the United States. It would be supported by Exact Sciences’ commercial infrastructure and ExactNexus technology platform, making electronic ordering and resulting seamless for more than 350 health systems.

The company also presented data from its multi-cancer early detection (MCED) blood test, assessing organ-specific performance of methylation and protein biomarkers in a prospectively collected cohort of samples from its ASCEND 2 study. The analysis indicated an overall sensitivity of 54.8% with 98.5% specificity in cancers without standard-of-care screening options (excluding lung) and 63.7% in the six most aggressive cancers with the shortest survival rates (esophagus, liver, lung, ovarian, pancreatic, and stomach). These findings highlight the potential clinical value of using multiple biomarkers to detect various cancer types, including the most aggressive and those without recommended screening options.

On September 16, 2024 Evaxion Biotech A/S (NASDAQ: EVAX) ("Evaxion"), a clinical-stage TechBio company specializing in developing AI-Immunology powered vaccines, reported positive one-year data from the ongoing phase 2 trial with its lead asset EVX-01, an AI-designed personalized cancer vaccine (Press release, Evaxion Biotech, SEP 16, 2024, View Source [SID1234646649]).

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"We are thrilled to present this groundbreaking data, which underscores the significant therapeutic potential of EVX-01. Among several promising individual data points, the 69% Overall Response Rate (ORR) is particularly impressive and encouraging. Building on an already strong data package for EVX-01, these new findings strengthen our confidence that we can meaningfully improve treatment options for advanced melanoma," says Birgitte Rønø, CSO of Evaxion.

"The clinical findings are another validation of our AI-Immunology platform as a leading AI technology for fast and effective vaccine target discovery and design and clearly positions us as a leader in the field of AI immunology. The observed reduction in tumors in 15 out of 16 patients is offering great hope for patients with melanoma. We are looking very much forward to engaging with stakeholders to present the compelling clinical profile of EVX-01 as a transformative personalized cancer vaccine," says Christian Kanstrup, CEO of Evaxion.

The data stems from a one-year interim analysis of the ongoing phase 2 trial investigating EVX-01 in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with advanced melanoma (skin cancer). The data was presented during the weekend at a poster session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 in Barcelona, Spain.

Unique profile of EVX-01 supported by both clinical efficacy and immune data
The data demonstrates 69% ORR, reduction in tumor target lesions in 15 out of 16 patients, an immunogenicity rate of 79%, and a positive correlation between Evaxion’s AI-Immunology platform predictions and immune responses induced by the individual neoantigens in the EVX-01 vaccine (p=0.00013). Neoantigens are newly formed antigens generated from cancer-specific mutations. As a neoantigen vaccine, EVX-01 aims at triggering the patient’s immune system to target these specific antigens and thereby eradicate the cancer cells.

The 69% ORR is calculated based on 11 out of 16 patients in the trial having objective clinical responses. This rate may increase as more data are collected but will not decrease. Final results are expected in the third quarter of 2025.

Further to the encouraging clinical data, the immunogenicity data from the trial are also impressive, demonstrating that 79% of EVX-01’s neoantigens triggered a targeted immune response. This immunogenicity rate stands out as unprecedented compared to historical observations and compares very favorably to what is seen with other approaches. It also underlines and validates the precision of the AI-Immunology platform in identifying neoantigens which leads to detectable signals in patients.

The new data also confirms the strong predictive capabilities of AI-Immunology with a positive correlation between its predictions and the neoantigen immune response detected in the patients with a p-value of p=0.00013. In other words, the data confirms that the neoantigens identified by the platform as the most relevant vaccine targets are also the ones that trigger specific immune responses in patients.

Significant commercial potential
The global burden from melanoma is estimated to increase to 510,000 new cases and 96,000 deaths by 2040 (Arnold et al., JAMA Dermatology 2022), and the global market for melanoma treatments is estimated to grow to $7.4 billion by 2029 (GlobalData).

Considering the prevalence of the disease and the size of the market, the development of EVX-01 as a novel potential melanoma treatment holds a significant commercial potential for Evaxion. As EVX-01 is also thought to have the potential to treat several other solid tumor cancers, the total commercial opportunity could be further enhanced by expanding into other indications.

Webinar on September 18

Evaxion will be hosting an online webinar featuring key opinion leader and the trial’s principal investigator, Professor Georgina V. Long, on September 18, 2024, at 19.00 CEST/13.00 EDT. The webinar can be attended through registration via this link.

In the webinar, Professor Long will present the data from the one-year interim analysis and discuss challenges in the medical treatment of advanced melanoma. In the end, a Q&A session will be held, and participants are encouraged to present questions.

About EVX-01

EVX-01 is a personalized peptide-based cancer vaccine intended for first-line treatment of multiple advanced solid cancers. It is Evaxion’s lead clinical asset.

EVX-01 is a personalized therapy designed with our AI-Immunology platform and is tailored to target the unique tumor profile and immune characteristics of each patient. It engages the patient’s immune system to fight off cancer by mounting a targeted response against tumors.

In the completed Phase 1/2a clinical trial (NCT03715985), assessing EVX-01 in combination with a PD-1 inhibitor, eight of twelve metastatic melanoma patients (67%) had objective clinical responses with two complete and six partial responses.

In addition, vaccine-induced T cells were detected in all patients and a significant correlation between clinical response and the AI-Immunology predictions was observed, underlining the predictive power of the platform.

About EVX-01 phase 2 clinical trial

The Phase 2 clinical study (NCT05309421) is a self-sponsored open-label, single-arm, multi-center trial carried out in collaboration with leading principal investigators and research centers from Italy and Australia. The trial aims to evaluate the efficacy and safety of EVX-01 vaccination in combination with MSD’s anti-PD1 therapy KEYTRUDA (pembrolizumab) in treatment-naive patients with metastatic or unresectable malignant stage III or IV melanoma. KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Merck Sharp & Dohme LLC supplies KEYTRUDA (pembrolizumab) for the trial.

On September 16, 2024 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on liver-directed cancer therapies, reported the presentation of new subgroup analysis data from the FOCUS Phase 3 trial of HEPZATO KIT (melphalan/Hepatic Delivery System (HDS)) in patients with metastatic uveal melanoma (mUM) (Press release, Delcath Systems, SEP 16, 2024, View Source [SID1234646648]). The data were presented by Dr. Matthew Wheater from University Hospital Southampton at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Barcelona.

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The FOCUS trial was a pivotal Phase 3 study designed to evaluate the efficacy and safety of HEPZATO KIT in patients with unresectable hepatic metastases from mUM. The primary endpoint of the study was objective response rate (ORR), with secondary endpoints including progression-free survival (PFS) and overall survival (OS). The trial enrolled 102 patients, of whom 91 received treatment. The full results of the FOCUS trial were published on May 4, 2024, in the Annals of Surgical Oncology.

The subgroup analysis evaluated patients with and without extrahepatic disease, treatment-naive versus previously treated patients, and those with low (1-25%) versus high (26-50%) liver tumor burden. There were no significant differences in OS, ORR, or PFS between patients with and without extrahepatic lesions or based on prior therapy. While ORR and PFS remained consistent regardless of liver tumor burden, more extensive liver involvement was associated with worse OS outcomes.

Objective tumor responses were observed throughout the entire treatment period; the earliest following completion of the first treatment cycle, and the latest following treatment cycle 6. This result supports the strategy to continue treatment until best response is achieved. Rates of serious adverse events (SAEs) and Grade 3/4 adverse events (AEs) remained consistent, indicating an absence of cumulative toxicity. These findings underscore the favorable benefit-risk profile of HEPZATO KIT in this patient population, offering a meaningful option for patients who typically have limited treatment options.

Dr. Wheater commented, "The lack of significant differences in outcomes between patients with and without extrahepatic disease is encouraging, particularly for a liver-directed therapy like Melphalan/HDS. Additionally, the fact that responses were observed through all six treatment cycles supports the strategy of continuing treatment beyond two cycles in patients with stable disease."

On September 16, 2024 Cytovation ASA, a clinical stage oncology company focused on the development of its first-in-class bifunctional immunotherapy CY-101 (CyPep-1) reported that it will deliver a poster presentation at ESMO (Free ESMO Whitepaper) 2024 entitled "Safety and activity of CY-101 in patients with advanced solid tumors: the Phase I/IIa CICILIA trial (Press release, Cytovation, SEP 16, 2024, View Source;utm_medium=rss&utm_campaign=cytovation-to-present-full-safety-and-efficacy-data-from-the-cicilia-phase-i-iia-trial-evaluating-cy-101-in-solid-tumors-at-esmo-2024 [SID1234646647])." Data from this study, evaluating intratumoral (IT) administration of CY-101 monotherapy and in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with heavily pretreated advanced solid tumors, show that CY-101 is well tolerated at the recommended Phase 2 dose (RP2D) of 20 mg. Furthermore, these data demonstrate early signs of antitumor activity, especially in tumors with dysregulated Wnt/β-catenin signaling.

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CY-101 is a synthetic peptide with a dual mode of action that both inhibits the oncogenic Wnt/β-catenin pathway by activating Axin2 and has a pore-forming membranolytic effect on cancer cells that exposes antigens and triggers a systemic tumor-specific immune response. Interim results from CICILIA were reported in 2023 (link to press release here) confirming that all trial endpoints were met, with CY-101 demonstrating a consistent safety profile across tumor types and strong early signals of efficacy.

Data from the ESMO (Free ESMO Whitepaper) poster show that no dose-limiting toxicities were observed in the dose- escalation part of the study with the RP2D defined at 20 mg. Analyses of paired tumor biopsies demonstrated induction of cancer cell death in >70% across tumor types at the RP2D, translating to a clinical benefit in several different cancer types. Notably, among six patients with adrenocortical carcinoma (ACC) receiving CY-101 monotherapy, a disease control rate of 50% (n = 3/6) was observed, with durable responses (> 6 months) in two patients. Both patients expressed β-catenin and had somatic mutations in the Wnt/β-catenin pathway.

Separately, the US Food and Drug Administration (FDA) has granted Orphan Drug Designation to CY-101 monotherapy for the treatment of ACC. Orphan Drug Designation is granted to investigational therapies that are intended for the treatment, diagnosis or prevention of rare diseases or conditions that affect fewer than 200,000 people in the US. Orphan Drug Designation provides several benefits to drug developers, including certain development cost benefits in the US, increased FDA interaction and eligibility for seven-year market exclusivity following approval.

"We believe CY-101 is a potentially important new treatment option that offers a truly differentiated approach to targeting Wnt/β-catenin driven cancers, an oncogenic pathway dysregulated in more than 20% of cancers," said Lars Prestergarden, CEO of Cytovation. "Our early data clearly confirm that CY-101 warrants further investigation in larger studies, and we are very pleased to receive Orphan Drug Designation for CY-101 in ACC. We look forward to advancing towards our planned Phase 2 trial in ACC with registrational intent."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merk & Co., Inc., Rahway, NJ, USA.

On September 16, 2024 Checkpoint Therapeutics, Inc. ("Checkpoint") (Nasdaq: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported the presentation of longer-term data from its pivotal trial of cosibelimab, its anti-programmed death ligand-1 ("PD-L1") antibody, in locally advanced and metastatic cutaneous squamous cell carcinoma ("cSCC") during the European Society for Medical Oncology ("ESMO") Congress 2024, which is taking place in Barcelona, Spain, from September 13 to 17, 2024 (Press release, Checkpoint Therapeutics, SEP 16, 2024, View Source [SID1234646646]).

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Poster Presentation Title: Cosibelimab in Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Longer-term Efficacy and Safety Results from Pivotal Study

"These longer-term results for cosibelimab presented at the ESMO (Free ESMO Whitepaper) Congress demonstrate a deepening of response over time, with higher objective response and complete response rates than initially observed at the primary analyses, and continue to expand the evidence supporting the efficacy and safety of cosibelimab as a potential new treatment for advanced cSCC," said James Oliviero, President and Chief Executive Officer of Checkpoint. "We look forward to our upcoming December 28, 2024, Prescription Drug User Fee Act ("PDUFA") goal date for our Biologics License Application for cosibelimab, and believe, if approved, cosibelimab’s dual mechanisms of action and safety profile may position the product, over time, as the preferred immunotherapy of U.S. oncologists."

Data highlights include:

Efficacy

With 16 months of additional follow-up since the primary analysis, cosibelimab demonstrated increasing objective response rates ("ORRs") and complete response rates per independent central review in 109 patients with advanced cSCC.
ORRs of 54.8% and 50.0% achieved in locally advanced and metastatic cSCC, with median follow-up durations of 24.1 and 29.3 months, respectively.
Results demonstrate a deepening of response over time, with complete response rates of 25.8% and 12.8% in locally advanced and metastatic cSCC, respectively.
Clinically meaningful durations of response ("DOR") were observed, with median DORs not yet reached in either group.
Safety

Overall, in 192 advanced cSCC patients treated with cosibelimab, a manageable safety profile was observed, with notable low rates of treatment-emergent adverse events ("TEAEs"), severe immune-related adverse events ("irAEs"), and treatment discontinuations.
3.6% of patients experienced an irAE assessed as grade 3, with no observed grade ≥4 irAEs.
No events of grade ≥3 pneumonitis, colitis, hepatitis, nephritis, or endocrinopathies.
Treatment discontinuation due to TEAEs, regardless of attribution, was observed in 12 patients (6.3%); the most common reason was COVID-19/COVID-19 pneumonia (1.6%).
A copy of the poster can be found on the Publications page of the Checkpoint Therapeutics website.

In December 2023, the U.S. Food and Drug Administration ("FDA") issued a complete response letter ("CRL") for the cosibelimab Biologics License Application ("BLA") for the treatment of patients with metastatic or locally advanced cSCC who are not candidates or curative surgery or radiation. The CRL only cited findings that arose during a multi-sponsor inspection of Checkpoint’s third-party contract manufacturing organization ("CMO") as approvability issues to address in a resubmission. In July 2024, Checkpoint announced it had completed a resubmission of the BLA to the FDA for cosibelimab to potentially address the approvability issues cited in the CRL. The resubmission was accepted by the FDA as a complete response and the FDA has set a PDUFA goal date of December 28, 2024.

About Cutaneous Squamous Cell Carcinoma (cSCC)
Cutaneous Squamous Cell Carcinoma is the second most common type of skin cancer in the United States, with an estimated annual incidence of approximately 1.8 million cases according to the Skin Cancer Foundation. Important risk factors for cSCC include chronic ultraviolet exposure and immunosuppressive conditions. While most cases are localized tumors amenable to curative resection, approximately 40,000 cases will become advanced, and an estimated 15,000 people will die from this disease each year. In addition to being a life-threatening disease, cSCC causes significant functional morbidities and cosmetic deformities based on tumors commonly arising in the head and neck region and invading blood vessels, nerves and vital organs such as the eye or ear. The immune-suppressed population represents a challenging target in the treatment of advanced cSCC, as they present with a more aggressive disease and with a higher risk of developing immune-related toxicities from checkpoint inhibitor treatment.

About Cosibelimab
Cosibelimab is a potential differentiated, high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to PD-L1 and blocks the PD-L1 interaction with the programmed death receptor-1 ("PD-1") and B7.1 receptors. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained high tumor target occupancy of PD-L1 to reactivate an antitumor immune response and the additional potential benefit of a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity ("ADCC") for potential enhanced efficacy.