On September 12, 2022 REVEAL GENOMICS, S.L., a Barcelona-based biotechnology start-up seeking to revolutionize precision oncology through biomarker innovation, reported another validation of HER2DX️, the world’s first specialized genomic test for HER2+ breast cancer (Press release, REVEAL GENOMICS, SEP 12, 2022, View Source [SID1234619479]).

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Her2dx
Her2dx
Prof. Valentina Guarneri from the University of Padova presented the data at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 held in Paris, France. The data obtained from the analysis of tumor samples from the PerELISA phase II clinical trial showed that the HER2DX️ pCR-score and the HER2DX️ ERBB2-score predicted the probability of a patient responding to the triple-drug combination of trastuzumab, pertuzumab and letrozole, when given before surgery (i.e., the neoadjuvant setting). These findings in patients with newly diagnosed HER2+/hormone receptor positive (HER2+/HR+) breast cancer can help identify better who might benefit from dual HER2 blockade with trastuzumab and pertuzumab.

"This is the first study to show the ability of HER2DX️ to predict response to trastuzumab and pertuzumab in the absence of chemotherapy. The performance of the test in PerELISA is remarkable and supports the predictive value of the test in the neoadjuvant setting", said Prof. Guarneri.

Dr. Aleix Prat, CSO of REVEAL GENOMICS️, added: "The ability of HER2DX️ to predict response to trastuzumab-based neoadjuvant therapies has now been demonstrated in more than 590 patients across 5 studies. Our commitment is to keep providing patients and physicians with the highest level of test evidence to help them make the right treatment decision".

HER2DX️ in the PerELISA trial

The PerELISA trial led by Prof. Valentina Guarneri and Prof. Pierfranco Conte, investigators from the University of Padova, evaluated the efficacy of a chemotherapy-free neoadjuvant regimen of trastuzumab and pertuzumab in 64 patients with HER2+/HR+ breast cancer. The results of the trial were published in 2019 in Annals of Oncology.

Patients recruited in PerELISA were first treated with 2-weeks of letrozole monotherapy and a tumor biopsy was performed. A relative decrease of Ki67 of more than 20% was observed in 44 (69%) patients; these patients continued in the trial and received trastuzumab, pertuzumab and letrozole for 5 cycles, after which surgery was performed. The overall response to this non-chemotherapy-based regimen, measured as the rate of pathological complete response (pCR), was observed in approximately 1 out of 5 patients.

HER2DX️ was evaluated in pre-treatment baseline tumor samples from 55 patients. HER2DX️ pCR score fairly accurately predicted the probability of responding to 2-weeks of letrozole monotherapy (AUC=0.780). In addition, in 40 patients who responded to letrozole and received 5 cycles of trastuzumab, pertuzumab and letrozole, HER2DX️ pCR score and HER2DX️ ERBB2-score predicted the probability of response with a good level of accuracy (AUC=0.80 and 0.90, respectively). The rates of pCR in HER2DX️ pCR-high, -medium and -low groups were 100%, 46% and 8%, respectively. The rates of pCR in HER2DX️ ERBB2-high, -medium and -low groups were 53%, 8% and 0%, respectively.

Results obtained in this new study endorse the value of HER2DX️ in predicting response to anti-HER2-based treatments before surgery and supports the prospective incorporation of HER2DX️ in dedicated trials focused on HER2+ breast cancer.

About HER2DX️

HER2DX️ is the world’s first diagnostic test formulated specifically for HER2+ breast cancer. Marketed by REVEAL GENOMICS️ since January 2022, the HER2DX is a standardized 27-gene expression test for patients with early-stage HER2+ breast cancer.

HER2DX️ is a prognostic and predictive assay based on clinical and genomic data. The test integrates clinical information (i.e., tumor size and nodal status) with biological information tracking immune response, luminal differentiation, tumor cell proliferation, and expression of the HER2 17q12-21 chromosomal amplicon, including the ERBB2 gene.

HER2DX️ predicts:

Risk of relapse score (high vs. low): the risk of recurrence in patients with newly diagnosed HER2+ breast cancer.
pCR likelihood score (high vs. medium vs. low): the likelihood of a patient responding to anti-HER2-based treatment before surgery.
ERBB2 score (high vs. medium vs. low): the quantitative expression of ERBB2 mRNA across HER2-negative, HER2-low and HER2+ breast cancer.
About HER2+ breast cancer

HER2+ breast cancer accounts for 20% of all diagnosed breast tumors. This represents more than 390,000 new cases diagnosed worldwide every year, meaning that, on average, 3 women are diagnosed with HER2+ breast cancer every 4 minutes. HER2+ breast cancer is clinically and biologically heterogeneous, and standard clinical-pathological assessment has proven insufficient in capturing this heterogeneity. Understanding this biological heterogeneity is key to identifying the prognosis of each patient and the benefit from systemic therapies that target HER2.

About this research collaboration

This study was led by investigators of the Translational Genomics and Targeted Therapeutics (TGTT) group at the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS, Barcelona, Spain) and the University of Padova (Italy). The HER2DX️ Research Use Only (RUO) test was performed at the TGTT laboratory.

On September 12, 2022 NeoImmuneTech, Inc. (NIT), a T cell-focused therapeutics company, reported data that suggests that NT-I7 plus pembrolizumab combination treatment enhances infiltration of PD-1+ T cells in cold tumors, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Paris, France, September 9-13, 2022 (Press release, NeoImmuneTech, SEP 12, 2022, View Source [SID1234619478]).

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While initial results from the phase 2a study NIT-110 had showed that subjects responding to NT-I7 plus pembrolizumab had enhanced lymphocyte infiltration, NeoImmuneTech conducted a new biomarker analysis of the immune-associated changes in the tumor microenvironment (TME) after NT-I7 plus pembrolizumab. The overall goal was to continue to understand how the combination of the long-acting human IL-7 and a checkpoint inhibitor (CPI) can induce a stronger immune response, since CPIs alone are usually considered ineffective in cold tumors with low T cell infiltration.

New data presented in a poster[1] at ESMO (Free ESMO Whitepaper) Congress 2022 suggest that the combination of NT-I7 and pembrolizumab induces infiltration of CD8 T cells into the tumor microenvironment in more than 80% of analyzed samples. The infiltration of CD8 T cells showed an increase of over 5-fold in over 50% of on-treatment samples after only one dose of NT-I7. Treatment with NT-I7 and pembrolizumab increased the immunogenicity of the TME. The analysis also revealed that treatment-induced reduction of the tumor volume was associated with the magnitude of CD8 T cell infiltration.

Dr. Se Hwan Yang, Ph.D., President and Chief Executive Officer of NeoImmuneTech said: "We continue to gather evidence to demonstrate that the combination of NT-I7 and pembrolizumab has promising clinical efficacy in very cold and immunosuppressive indications. Our latest data presented at ESMO (Free ESMO Whitepaper) indicate that the enhanced tumor-specific CD8 T cell infiltration into the tumor microenvironment may trigger enhanced clinical efficacy. This represents an encouraging path to potentially provide one day more therapeutic options to patients with cold tumors where CPIs are usually ineffective."

About NT-I7 (efineptakin alfa) (rhIL-7-hyFc)

NT-I7 (efineptakin alfa) is the only clinical-stage long-acting human IL-7 and is being developed in oncologic and immunologic indications, where T cell amplification and increased functionality may provide clinical benefit. IL-7 is a fundamental cytokine for naïve and memory T cell development and sustaining immune response to chronic antigens (as in cancer) or foreign antigens (as in infectious diseases). NT-I7 exhibits favorable PK/PD and safety profiles, making it an ideal combination partner. NT-I7 is being studied in multiple clinical trials in solid tumors and as vaccine adjuvant. Studies are being planned for testing in hematologic malignancies, additional solid tumors and other immunology-focused indications.

On September 12, 2022 Cytovia Therapeutics, Inc., a biopharmaceutical company empowering natural killer (NK) cells to fight cancer through stem cell engineering and multispecific antibodies, reported that it is presenting new preclinical data for its GPC3 Flex-NK cell engager antibody in combination with natural killer cells at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper)’s annual congress in Paris, France on September 12th, 2022 (Press release, Cytovia Therapeutics, SEP 12, 2022, View Source [SID1234619477]).

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The poster is available on both Cytovia and ESMO (Free ESMO Whitepaper)’s websites and will be displayed from 9AM-5PM CET and presented from 12PM-1PM CET on Monday, September 12th, 2022 (Poster Session 13, Hall 4, Abstract 756P).

Background: GPC3 is an oncofetal antigen that is highly expressed in HCC while it is hardly expressed in adult normal tissues except placenta. CYT-303 is a multifunctional bispecific NK cell engager built on our Flex-NKTM scaffold, which engages NK cells through NKp46 and targets GPC3 expressed on tumor cells.

Conclusions:

CYT-303 showed dose-dependent HCC tumor growth inhibition in PBNK and iNK cell injected HCC tumor models.
Dose-dependent increases in CYT-303 concentrations in tumor and blood were observed in the PBNK injected HCC tumor model showing the potential for CYT-303 to penetrate solid tumors.
CYT-303 treated animals showed significant decreases in blood PBNKs suggesting CYT-303 may facilitate trafficking of these cells from blood to the tumor.
Bell shaped dose-response observed with CYT-303 monotherapy in the PBNK injected HCC tumor model is consistent with CYT-303 in vitro studies showing similar dose-responses for PBNK and HCC tumor binding and tumor cytolysis.
The linear dose-response observed with CYT-303 combination therapy with iNK cells in the HCC tumor model is consistent with the in vitro linear dose-response observed with iNK combination for cytolysis of HCC tumors.
CYT-303 treatment resulted in reductions in blood AFP levels in both the PBNK and iNK injected HCC tumor models showing the utility of this biomarker for CYT-303 clinical studies.
These CYT-303 preclinical proof-of-concept studies support clinical development of CYT-303 in HCC.

On September 12, 2022 Delfi Diagnostics, a pioneering developer of a new class of high-performance, accessible liquid biopsy tests for early cancer detection and monitoring, reported that has been selected as the liquid lung cancer biopsy partner in Europe’s multi-national, randomized, prospective lung cancer screening trial known as 4-IN-THE-LUNG-RUN, or 4ITLR (Press release, Delfi Diagnostics, SEP 12, 2022, View Source [SID1234619476]).

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Through 4ITLR, European investigators are studying how often – every year, or every other year – individuals should get screened if their initial CT scan is negative. Delfi’s technology is paired to the study objectives by measuring whether Delfi can identify individuals in Europe’s screen-eligible population who are most likely to benefit from a CT scan. The collaboration, initiated and facilitated through a partnership between the Netherlands Cancer Institute ((NKI), with Dr. D. van den Broek as PI) and the institute for DiagNostic Accuracy (iDNA), includes Delfi analyzing the first 9,000 subjects enrolled through the trial in the Netherlands and France (Gustave Roussy) – generating data that can support Delfi’s research and subsequent implementation within the European Union.

"One of the goals of our study is to examine how a liquid biopsy test might improve screening in a manner that is cost-effective," said prof. Matthijs Oudkerk, MD, PhD, Chief Scientific Officer at iDNA and leading the Radiology and AI readings of 4ITLR. "We are eager to explore how a low-cost liquid biopsy platform could help us screen more high-risk Europeans."

Based on the results of the NELSON trial, the European Union is expected to initiate a European lung cancer screening program for individuals at risk due to their smoking and age.

"We know that LDCT screening is effective in reducing lung cancer mortality," said Peter B. Bach, Delfi Diagnostics Chief Medical Officer. "This study should lay the groundwork for widespread, cost efficient screening of those at risk in Europe. Delfi is honored to be part of it."

Lung cancer kills more than 380,000 Europeans each year, and more than half of all new lung cancer diagnoses in Europe occur at stage IV, when 5-year survival rates can be as low as 2 percent. But screening older heavy smokers with low-dose CT could save up to 80,000 lives in Europe per year.

On September 12, 2022 Shasqi, a clinical-stage biotechnology company developing oncology therapeutics with its proprietary Click Activated Protodrugs Against Cancer (CAPAC ) platform reported it has opened the Phase 2 of their Phase 1/2a clinical study to further assess SQ3370 in anthracycline- naïve patients (Press release, Shasqi, SEP 12, 2022, View Source [SID1234619475]). The Phase 2 study follows the company’s presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, held September 9-13, 2022, evaluating the safety, tolerability, maximum tolerated dose, and recommended Phase 2 dose for SQ3370 in patients with locally advanced and/or metastatic solid tumors (NCT04106492).

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"We are encouraged by the promising results from our Phase 1 study and preclinical data which indicate that click chemistry in humans has the potential to revolutionize cancer care by expanding the therapeutic index of anti-cancer therapies such as doxorubicin," said José M. Mejía Oneto, M.D., Ph.D., Founder and CEO of Shasqi. "We look forward to further exploring the safety and efficacy of our lead candidate SQ3370 at unprecedented dose levels in the Phase 2 study."

The Phase 1 clinical data were presented as a poster during the congress:

Abstract Title: Phase 1 Clinical & Immunologic Data of SQ3370 in Advanced Solid Tumors
Presentation Number: 1499P
Poster Session Title: Phase 1 Clinical & Immunologic Data of SQ3370 in Advanced Solid Tumors
Link to full poster details here.
Key Phase 1 study findings include:

SQ3370 was well tolerated among 27 DLT evaluable patients receiving up to 12x (1x equals 75mg/m2/cycle of Dox molar equivalents); maximum tolerated dose has not been reached
Among patients treated with a least one cycle of SQ3370, no protocol defined dose-limiting toxicities, including anthracycline myelosuppression and gastrointestinal (GI) toxicity, were observed and no treatment emergent adverse events (TEAEs) that led to death were considered related to SQ3370; the most frequent Grade ≥3 TEAE was anemia
The highest doses tested of SQ3370 led to immune activation in soft tissue sarcomas which are considered immunologically cold tumors, validating preclinical findings of SQ3370 previously published:
Increased cytotoxic T-cell activity observed at higher dose levels of SQ3370 indicate immune activation and a trend toward increase in tumor cell death in heavily pretreated patients
Immune activation has the potential to improve systemic activity of intra-tumoral administration of SQ3370 which will be explored in Phase 2
"Early data has shown that click chemistry allows for the release of doxorubicin at the tumor site to generate anti-tumor responses. Phase 1 results showing that SQ3370 is well-tolerated among a heavily pretreated patient population further validate this clinical approach and the importance of investigating SQ3370 as a potential treatment option in patients with anthracycline-sensitive- and other solid tumors," said Sant P. Chawla, M.D., FRACP, Principal Investigator, and Head, Sarcoma Oncology Center in Santa Monica, California."

Shasqi is excited to open the Phase 2 study of SQ3370 in anthracycline-naïve patients with advanced soft tissue sarcomas, relapsed or recurrent squamous-cell head and neck cancer, platinum refractory ovarian cancer recurrent and/or metastatic uterine carcinoma, or uterine sarcoma. For more information, visit www.shasqi.com