On February 26, 2024 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) reported an update on the positive results of OSE-279 in the Phase 1/2 clinical evaluation in advanced solid tumors at the 2024 ESMO (Free ESMO Whitepaper) Targeted Anticancer Therapies Congress (ESMO TAT) held in Paris, France (February 26 – 28, Abstract #368; FPN 30P) (Press release, OSE Immunotherapeutics, FEB 26, 2024, View Source [SID1234640481]).

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Silvia Comis, Head of Clinical Development and Regulatory Affairs of OSE Immunotherapeutics, comments: "We are very pleased to share this positive update on the preliminary efficacy and safety results from a Phase 1/2 study assessing the therapeutic potential of our proprietary high affinity anti-PD1 monoclonal antibody OSE-279 in advanced solid tumors. These new results and additional signal of efficacy with a high anti-tumor response rate in difficult-to-treat patients, highlight the value of OSE-279 as a potential strong anti-PD1 therapy and encourage further clinical development in the future in pre-identified cancer niche indications, with still high unmet medical needs. In parallel to OSE-279 monotherapy development, new cohort testing combinations with other OSE drug candidates, including cancer vaccine, are being explored."

The ESMO (Free ESMO Whitepaper)-TAT communication reported on the positive results from the Phase 1/2 clinical trial (NCT05751798) evaluating OSE-279 monotherapy in patients with advanced solid tumors, with no therapeutic option available.

The updated data show a good pharmacokinetic/pharmacodynamic (PK/PD) and manageable safety profile in line with previous anti-PD1 development and with a high signal of efficacy in the first 20 patients representing 13 different tumor types. Four confirmed ongoing partial responses (PR) with 600 mg every six weeks (q6w), with a response rate of 36%, were reported in patients with anal squamous cell carcinoma, undifferentiated pleomorphic sarcoma, oncocytic thyroid cancer, and alveolar soft part sarcoma. One still ongoing confirmed PR (81% reduction of target lesions) has been observed in a patient with hepatocellular carcinoma after one single dose of OSE-279 300 mg. Five stable diseases (SD) were reported at multiple dose levels. Treatment is ongoing in seven patients. Pharmacokinetic (PK) showed dose-proportionality and favorable exposure. Receptor occupancy (RO) was maintained. At 600 mg q6w, no dose-limiting toxicities (DLTs) were reported in 10 patients. Further to the recommendation of a Phase 2 dose (RP2D) of 300 mg q3w, the dose of 600 mg q6w has been selected as the second RP2D.

OSE-279 is a high affinity humanized anti-PD1 monoclonal antibody blocking both PD-L1 and PD-L2, the ligands of PD1 overexpressed by tumor cells and tumor microenvironment. Overexpression of PD-L1 and PD-L2 on tumor and myeloid cells in the tumor microenvironment is a mechanism of tumor immune escape.

Given the advantages of owning a proprietary and protected high affinity anti-PD1 antagonist antibody, OSE Immunotherapeutics has developed a global intellectual property strategy protecting OSE-279 until at least 2039. This has been achieved through recent grants of patents in the U.S., various European countries, China, Japan, Korea, Australia, and Mexico to date. These patents protect the original antibody sequences of OSE-279 associated with its innovative biological and manufacturing properties.

The first-in-human open label Phase 1/2 dose escalation and expansion study, initiated in December 2022, aims to determine the Maximum Tolerated Dose (MTD) and/or the RP2D of OSE-279 as a monotherapy in advanced solid tumors with two possible administration regimens. Secondary objectives include assessment of OSE-279’s antitumor activity, evaluation of the safety profile, pharmacokinetic and receptor occupancy or pharmacodynamic profile (NCT05751798).

On February 26, 2024 Bayer reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for BAY 2927088 for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have received a prior systemic therapy (Press release, Bayer, FEB 26, 2024, View Source [SID1234640480]). BAY 2927088 is an oral, reversible tyrosine kinase inhibitor (TKI) that potently inhibits mutant human epidermal growth factor receptors 2 (HER2), including HER2 exon 20 insertions and HER2 point mutations, as well as epidermal growth factor receptors (EGFR), with high selectivity for mutant vs wild-type EGFR.1,2

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Lung cancer is the leading cause of cancer-related deaths worldwide.3 NSCLC is the most common type of lung cancer, accounting for more than 85% of cases.4 Activating HER2 mutations are found in 2% to 4% of advanced NSCLC.5 Currently there are no available therapies that have received full approval in the U.S. for patients with NSCLC in the metastatic or advanced setting harboring HER2 activating mutations.

The Breakthrough Therapy designation is supported by preliminary clinical evidence from the Phase I, open-label, multicenter first-in-human study (NCT05099172) evaluating the safety, pharmacokinetics and preliminary efficacy of BAY 2927088 in adult patients with advanced NSCLC harboring HER2 or EGFR.

"Early clinical evidence suggests that BAY 2927088, our investigational novel oral tyrosine kinase inhibitor, has the potential to benefit patients with NSCLC harboring a HER2 mutation that have progressed on a prior systemic therapy and currently have no other approved treatment available," said Dominik Ruettinger, M.D., Ph.D., Head of Research and Early Development for Oncology at Bayer’s Pharmaceuticals Division. "This Breakthrough Therapy designation is a significant milestone in our relentless efforts to develop innovative therapies for the treatment of lung cancer characterized by specific genomic markers. We will continue working closely with the FDA to advance BAY 2927088 through the clinic and look forward to providing these patients with lung cancer and their physicians with a targeted, effective treatment option."

The FDA’s Breakthrough Therapy designation is intended to expedite the development and review of drug candidates that treat serious or life-threatening diseases or conditions, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies.6

BAY 2927088 was derived from Bayer’s long-standing strategic research alliance with the Broad Institute of MIT and Harvard in Cambridge, MA, USA.

On February 26, 2024 Bayer reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for BAY 2927088 for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have received a prior systemic therapy (Press release, Bayer, FEB 26, 2024, View Source [SID1234640480]). BAY 2927088 is an oral, reversible tyrosine kinase inhibitor (TKI) that potently inhibits mutant human epidermal growth factor receptors 2 (HER2), including HER2 exon 20 insertions and HER2 point mutations, as well as epidermal growth factor receptors (EGFR), with high selectivity for mutant vs wild-type EGFR.1,2

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Lung cancer is the leading cause of cancer-related deaths worldwide.3 NSCLC is the most common type of lung cancer, accounting for more than 85% of cases.4 Activating HER2 mutations are found in 2% to 4% of advanced NSCLC.5 Currently there are no available therapies that have received full approval in the U.S. for patients with NSCLC in the metastatic or advanced setting harboring HER2 activating mutations.

The Breakthrough Therapy designation is supported by preliminary clinical evidence from the Phase I, open-label, multicenter first-in-human study (NCT05099172) evaluating the safety, pharmacokinetics and preliminary efficacy of BAY 2927088 in adult patients with advanced NSCLC harboring HER2 or EGFR.

"Early clinical evidence suggests that BAY 2927088, our investigational novel oral tyrosine kinase inhibitor, has the potential to benefit patients with NSCLC harboring a HER2 mutation that have progressed on a prior systemic therapy and currently have no other approved treatment available," said Dominik Ruettinger, M.D., Ph.D., Head of Research and Early Development for Oncology at Bayer’s Pharmaceuticals Division. "This Breakthrough Therapy designation is a significant milestone in our relentless efforts to develop innovative therapies for the treatment of lung cancer characterized by specific genomic markers. We will continue working closely with the FDA to advance BAY 2927088 through the clinic and look forward to providing these patients with lung cancer and their physicians with a targeted, effective treatment option."

The FDA’s Breakthrough Therapy designation is intended to expedite the development and review of drug candidates that treat serious or life-threatening diseases or conditions, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies.6

BAY 2927088 was derived from Bayer’s long-standing strategic research alliance with the Broad Institute of MIT and Harvard in Cambridge, MA, USA.

On February 26, 2024 Biodesix, Inc. (Nasdaq: BDSX), a leading diagnostic solutions company with a focus in lung disease, reported that Scott Hutton, Chief Executive Officer of Biodesix, will present and host in-person 1×1 investor meetings at the TD Cowen 44th Annual Health Care Conference, which will be held from March 4-6, 2024 (Press release, Biodesix, FEB 26, 2024, View Source [SID1234640479]).

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TD Cowen 44th Annual Health Care Conference
Presentation Date: Monday, March 4, 2024
Presentation Time: 10:30 AM ET
Location: Marriot Copley Place, Boston, MA

The presentation will be webcast live and available for replay under "News & Events" in the Investors section of Biodesix’s website at Biodesix.com.

On February 26, 2024 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported the publication of a study in Cancers demonstrating that DecisionDx-Melanoma provided significantly better risk stratification than American Joint Committee on Cancer 8th Edition (AJCC8) staging in patients with stage I cutaneous melanoma (CM) (Press release, Castle Biosciences, FEB 26, 2024, View Source [SID1234640478]). This study reports the results of two large stage I cohorts, including 5,651 patients from the National Cancer Institute’s SEER Program Registries (analyzing survival) and 1,261 patients from a combined cohort (analyzing recurrence and survival), and suggests that incorporating the DecisionDx-Melanoma test into clinical practice may help clinicians and patients obtain more precise information about a patient’s prognosis to inform more personalized, risk-aligned treatment and surveillance management plans.

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"Relying on staging alone to determine a melanoma patient’s prognosis misses patients with aggressive tumor biology who may be at higher risk of recurrence, metastasis or death from their disease," said Sebastian Podlipnik, M.D., Ph.D., lead study author and dermatologist at the Hospital Clínic de Barcelona, Universitat de Barcelona, in Spain. "As supported by the data in this study, incorporating DecisionDx-Melanoma test results into clinical decision-making can help identify which patients with lower stage tumors may be at higher risk of disease progression and could benefit from more aggressive follow-up schedules and treatment plans to identify recurrence earlier when it has generally been shown to have better treatment outcomes."

Traditionally, treatment pathways for CM have been based upon clinicopathologic AJCC8 staging, which provides population-based risk of progression estimates. Stage I CM tumors are considered low risk; however, since stage I encompasses a large group of patients diagnosed, many melanoma-specific deaths are seen in patients initially diagnosed with stage I disease. Thus, there is a clinical gap in the low-risk treatment pathway for stage I patients. DecisionDx-Melanoma was developed and validated to provide a tumor-specific risk of recurrence, independent of the current risk factors used in AJCC8 staging, specifically tumor thickness and ulceration. The test classifies patients as having a low risk (Class 1A), intermediate risk (Class 1B/2A) or high risk (Class 2B) of tumor recurrence, metastasis and melanoma-specific mortality based on the patient’s tumor biology. As a result of this risk-stratification information, DecisionDx-Melanoma is used clinically to help inform patient-specific treatment pathway decisions.

The new study in Cancers provides further information that DecisionDx-Melanoma testing could enable more precise risk stratification in stage I melanomas than provided by traditional staging to better inform risk-appropriate clinical management. This multi-center study analyzed data from nearly 7,000 patients with stage I CM to assess their five-year recurrence-free survival (RFS) and melanoma-specific survival (MSS) using the DecisionDx-Melanoma test. There were two cohorts of patients: a pooled cohort from previous studies (combined cohort, n=1,261) and a second, large, real-world cohort of unselected patients who received the DecisionDx-Melanoma test as part of their clinical care (patients diagnosed with CM between 2013–2018 who were linked to outcomes data from the National Cancer Institute’s SEER Program registries, n=5,651). The combined cohort was evaluated for RFS and MSS, and the SEER cohort was evaluated for MSS.

In both cohorts, DecisionDx-Melanoma provided greater separation between patients with high- and low-risk test results than seen between AJCC8 stage IA and IB, demonstrating the ability of the test to provide improved risk stratification over staging.

Combined cohort

Separation of risk

RFS stratification

DecisionDx-Melanoma test results

Class 1A (low risk) (97.3%) vs. Class 2B (high risk) (77.3%); p < 0.001

AJCC8 staging

Stage IA (97.5%) vs. IB (89.3%); p < 0.001

SEER cohort

Separation of risk

MSS

stratification

DecisionDx-Melanoma test results

Class 1A (low risk) (98.0%) vs. Class 2B (high risk) (92.3%); p < 0.001

AJCC8 staging

Stage IA (97.6%) vs. stage IB (97.9%); p < 0.001

In the combined cohort, multivariable analysis showed that a DecisionDx-Melanoma Class 2B test result was the strongest predictor of recurrence in stage I CM (HR = 5.16, p < 0.001); similarly, in the SEER cohort, multivariable analysis indicated that a high-risk test result was the only significant predictor of melanoma-specific mortality in stage I patients (HR = 9.23, p < 0.001).

The data in this study support the use of DecisionDx-Melanoma to help guide improved, risk-aligned care in patients considered low risk by staging (i.e., patients with stage I CM tumors) but who have aggressive molecular tumor biology and may be missed using only staging criteria for prognosis.

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile risk stratification test. It is designed to inform two clinical questions in the management of cutaneous melanoma: a patient’s individual risk of sentinel lymph node (SLN) positivity and a patient’s personal risk of melanoma recurrence and/or metastasis. By integrating tumor biology with clinical and pathologic factors using a validated proprietary algorithm, DecisionDx-Melanoma is designed to provide a comprehensive and clinically actionable result to guide risk-aligned patient care. DecisionDx-Melanoma has been shown to be associated with improved patient survival and has been studied in more than 10,000 patient samples. DecisionDx-Melanoma’s clinical value is supported by 50 peer-reviewed and published studies, providing confidence in disease management plans that incorporate the test’s results. Through Sept. 30, 2023, DecisionDx-Melanoma has been ordered more than 146,000 times for patients diagnosed with cutaneous melanoma.