On May 23, 2024 OncoHost, a technology company transforming the approach to precision medicine for improved patient outcomes, reported that it has been accepted for a poster presentation at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held from May 31 to June 4, 2024, in Chicago, Illinois (Press release, OncoHost, MAY 23, 2024, View Source [SID1234643638]). The presentation will highlight the ability of the company’s PROphet platform to predict clinical benefit from immune checkpoint inhibitor (ICI)-based therapies across various cancer indications.

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"ICIs represent a key treatment modality for a growing number of cancer types, but a gap exists in the availability of predictive tests that can accurately identify patients likely to benefit from these therapies. Our PROphet platform offers a solution," said Ofer Sharon, MD, CEO at OncoHost. "This research highlights the adaptability of PROphet as we work to provide treatment guidance for multiple indications. I am proud of our team’s commitment to improving outcomes for cancer patients worldwide and the ongoing impact of our work in the oncology field."

PROphet is a novel and robust predictive computational model that analyzes and identifies proteomic profiles in pre-treatment blood plasma by combining bioinformatics, system biology, proteomic pattern recognition and machine learning. PROphetNSCLC, the first indication for which the platform was developed, predicts clinical benefit from first-line PD-1/PD-L1 inhibitor-based therapies in patients with metastatic non-small cell lung cancer (mNSCLC), offering guidance in choosing between ICI monotherapy and ICI-chemotherapy combination.

For this observational study, pre-treatment plasma samples and clinical data were collected from patients with metastatic melanoma and HPV-related cancers undergoing treatment with PD-1/PD-L1 inhibitor-based therapies. HPV-related cancers included anogenital squamous cell carcinoma, cervical carcinoma, and head and neck squamous cell carcinoma. The presentation will showcase the findings which demonstrate the potential of the PROphetNSCLC test in predicting ICI response for indications beyond just NSCLC, underscoring the promise of PROphet in advancing precision medicine.

The study was conducted in collaboration with Sidney Kimmel Medical College at Thomas Jefferson University, Yale School of Medicine, and the Center for Immuno-Oncology, Center for Cancer Research of the National Cancer Institute.

"We are excited to present our latest findings at ASCO (Free ASCO Whitepaper) 2024," said Itamar Sela, Ph.D., VP R&D at OncoHost and co-author of the study. "This study showcases the versatility of the PROphet platform in predicting benefit from immune-checkpoint inhibitors not only in NSCLC, but also in melanoma and HPV-related cancers. By leveraging the power of plasma-based proteomic analysis, PROphet offers a non-invasive and efficient method to guide treatment decisions and optimize patient care."

Poster Presentation Details
Session: Developmental Therapeutics—Immunotherapy
Abstract #: 2568
Poster Bd #: 47
Title: A plasma-based proteomic platform for predicting clinical benefit from immune checkpoint inhibitors in multiple cancers.
Presenter: Itamar Sela, Ph.D., VP R&D at OncoHost
Date/Time: 6/1/2024, 9:00 AM-12:00 PM CDT

The abstract is available on the ASCO (Free ASCO Whitepaper) website.

On May 23, 2024 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, reported that clinical and biomarker data from its ST101 Phase 2 study in GBM will be delivered during an oral presentation on June 1, 2024 at the upcoming 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Sapience Therapeutics, MAY 23, 2024, View Source [SID1234643637]).

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ST101 is a first-in-class antagonist of C/EBPβ, currently being evaluated in patients with recurrent and newly diagnosed GBM in the Phase 2 portion of an ongoing Phase 1-2 clinical study (NCT04478279).

Sapience’s Chief Medical Officer, Abi Vainstein-Haras, MD, stated, "We are encouraged by ST101’s clinical and biomarker data for patients with glioblastoma. This novel therapy has the potential to be a new treatment opportunity for this devastating disease, and we are honored to be presenting these promising results in an oral presentation at ASCO (Free ASCO Whitepaper) 2024. We are committed to bringing new hope to patients battling glioblastoma and look forward to advancing ST101 through clinical development."

Dr. Fabio M. Iwamoto, Division of Neuro-Oncology, New York-Presbyterian/Columbia University Irving Medical Center, and Principal Investigator of the ST101-101 clinical study added, "Current treatments for recurrent glioblastoma offer limited hope for patients. I’m enthusiastic about the potential of ST101. It represents a novel approach with the potential to extend survival, both as a standalone therapy and in combination with existing treatments. Importantly, ST101’s safety profile suggests it could be well-tolerated, potentially offering a significant benefit for patients battling this aggressive disease."

Oral presentation details and abstract highlights include:

Abstract Title: "Efficacy and biomarker analysis of phase 2 (P2) and window-of-opportunity (WoO) cohorts of patients with glioblastoma (GBM) treated with ST101, an inhibitor of the transcription factor C/EBPβ"
Abstract Number for Publication: 2011
Session Type and Title: Clinical Science Symposium – Advancing Trial Design: Illuminating Tumor Evolution in Central Nervous System Cancer
Date and Time: 6/1/2024, 3:00 PM-4:30 PM CDT
Presenting Author: Fabio M. Iwamoto, MD, Division of Neuro-Oncology, New York-Presbyterian/Columbia University Irving Medical Center

ST101 has the potential to be a well-tolerated treatment option for patients with GBM

Outcome data to be presented from multiple cohorts of GBM patients
Main study: monotherapy in recurrent GBM
Window-of-Opportunity Study: mono/combination-therapy in GBM
Biomarker data to be presented from Window-of-Opportunity study cohorts
ST101 crosses the BBB and penetrates tumor tissue as shown by IHC
Target (C/EBPβ) engagement and degradation shown by IHC
Modulation of the tumor immune microenvironment to promote anti-tumor activity
Data supports continued clinical development of ST101 as a backbone treatment in combination with standard of care and immune-oncology agents.
The slide presentation described here will be made available on the Sapience Therapeutics website following the conference.

About ST101
ST101, a first-in-class antagonist of C/EBPβ, is currently being evaluated in patients with newly diagnosed and recurrent GBM (ndGBM and rGBM) in the Phase 2 portion of an ongoing Phase 1-2 clinical study (NCT04478279). In an ongoing window-of-opportunity sub-study, ST101 is being evaluated as a monotherapy in rGBM and in combination with radiation and temozolomide in ndGBM, with patients receiving ST101 before and after surgical resection. ST101 has been granted Fast Track designation for rGBM from the U.S. FDA and orphan designations for glioma from the U.S. FDA and the European Commission.

On May 23, 2024 Aadi Bioscience, Inc. (NASDAQ: AADI), a commercial-stage precision oncology company focused on developing and commercializing therapies for cancers with alterations in the mTOR pathway, reported new nonclinical data demonstrating the significantly higher intratumoral drug concentration, stronger inhibition of mTOR targets and greater antitumor activity of nab-sirolimus compared to intravenous and oral mTOR inhibitors in a xenograft model (Press release, Aadi Bioscience, MAY 23, 2024, View Source [SID1234643636]). These data will be available as an abstract and published in the Journal of Clinical Oncology supplement to coincide with the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place May 31 – June 4, 2024.

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"Our goal at Aadi is to unlock the full power of mTOR inhibition by combining nanoparticle albumin bound (nab) technology with sirolimus to improve delivery, stability, solubility and targeting," said Loretta Itri, MD, Chief Medical Officer at Aadi. "With superior findings across key markers, these important nonclinical data add to our growing body of evidence that nab-sirolimus may overcome limitations of previous therapies, including both orally and intravenously delivered mTOR inhibitors, with the potential to play an important therapeutic role in difficult-to-treat cancers."

Abstract details and highlights include:

Title: Antitumor activity of nab-sirolimus versus mTOR inhibitors temsirolimus, sirolimus, and everolimus in A549 NSCLC xenografts
Lead Author: Shihe Hou
Abstract: View Source

Despite the broad importance of the mTORC1 pathway in cancer cell growth and survival, mTOR inhibitors (mTORis) temsirolimus, sirolimus and everolimus have limited clinical application in the cancer setting.
In A549 xenografts, nab-sirolimus resulted in significantly greater suppression of tumor growth compared with IV temsirolimus and oral sirolimus and everolimus.
Average intratumoral drug concentrations 24 hours after IV mTORi treatment were significantly higher with nab-sirolimus (420-539 ng/g) compared with temsirolimus (34.9 ng/g) and its active metabolite (13.2 ng/g); similarly, tumor uptake of nab-sirolimus greatly exceeded that of sirolimus and everolimus at steady-state.
We believe these results support further clinical evaluation of nab-sirolimus as a single agent or in combination with other therapeutic agents.
In addition, Aadi will present a trials-in-progress poster on its Phase 2 trial in advanced or recurrent endometrioid-type endometrial cancer (EEC), a difficult-to-treat mTOR-driven cancer. Endometrial cancer is the most common cancer of the female reproductive organs and one of the few cancers with increasing mortality. There are an estimated 10,000 cases of EEC diagnosed annually.

Poster details and abstract highlights include:

Title: A phase 2, open-label, single-arm, prospective, multicenter study of nab-sirolimus plus letrozole in advanced or recurrent endometrioid endometrial cancer
Presenting Author: Lauren Dockery, MD, MS
Session Title: Poster Session – Gynecologic Cancer
Abstract Number: TPS5640
Date/Time: Monday, June 3rd, 9:00 am – 12:00 pm

This is a Phase 2 open-label, multi-institutional study to evaluate the efficacy and safety of nab-sirolimus and letrozole in patients with advanced or recurrent endometrioid endometrial carcinoma, exploring the potential for this combination to produce additive anti-tumor activity in patients with EEC.
Dysregulation of mTOR signaling is implicated in the pathology of EEC, in which >80% harbor PTEN or PI3K/AKT/mTOR pathway alterations.
Prior clinical studies with mTOR inhibitors and letrozole in endometrial cancer patients have yielded promising results.
Alternative treatment options for patients with advanced or recurrent EEC remain necessary despite recent pivotal data demonstrating improved outcomes with immunotherapy plus chemotherapy.

On May 23, 2024 Rutgers Cancer Institute and RWJBarnabas Health reported that its Clinicians and scientists will lead sessions and present their latest discoveries from their innovative cancer research program at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held in Chicago (and online) from May 30-June 4 (Press release, Rutgers Cancer Institute of New Jersey, MAY 23, 2024, View Source [SID1234643635]). A total of 49 accepted abstracts and presentations will cover cutting-edge topics, including two oral sessions highlighting the National Surgical Quality Improvement Program (NSQIP) audit of enhanced recovery after surgery protocols for radical cystectomy, as well as social vulnerability and clinical trial enrollment’s role in the next frontier of health equity.

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"Our world-renowned integrated network of researchers and clinicians at Rutgers Cancer Institute and RWJBarnabas Health continues to innovate and investigate strategies that will achieve the best possible outcomes for our patients. This is reflected in the dynamic lineup of presentations featured at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, underscoring our team’s commitment and dedication," said Steven K. Libutti, MD, FACS, Director, Rutgers Cancer Institute and Senior Vice President, Oncology Services, RWJBarnabas Health. "As New Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center and the leading cancer program in the state, we are at the forefront of advancing cancer research and care to conquer a disease that impacts so many. We look forward to sharing our array of recent advancements and findings at this year’s meeting."

The research accepted for presentation at ASCO (Free ASCO Whitepaper) includes one late-breaking abstract, oral and poster sessions as well as publication-only abstracts highlighting data in numerous types of cancer, including breast, colorectal, lymphoma, and lung.

Highlights of the accepted abstracts include the following:

Findings from a study that assesses how social vulnerability impacts clinical trial enrollment and explores the interaction between race and social vulnerability among patients with one of the top five cancers – breast, prostate, lung, colorectal and pancreas. Findings confirm that neighborhood social vulnerability is a barrier to trial enrollment, even more so among Black patients.
Utilization of enhanced recovery after surgery (ERAS) protocols for radical cystectomy has been associated with improved postoperative recovery and shorter hospital stays. This study was designed to assess the impact of increasing compliance to ERAS components on postoperative outcomes in patients who underwent radical cystectomy. Researchers reviewed 3,708 patients from the National Surgical Quality Improvement Program database who underwent radical cystectomy from 2019 – 2021.
Updates from CTEP 10492, a Phase 1/1b study investigating the AKT inhibitor ipatasertib with chemoradiation to treat locally advanced head and neck squamous cell carcinoma (HNSCC). The primary objective of this study is to determine the maximum tolerated dose and recommended Phase 2 dose of ipatasertib in combination with definitive chemoradiation therapy (CRT) in locally advanced HNSCC based on dose-limiting toxicities. This phase 1/1b study will be the first to establish safety and preliminary efficacy of ipatasertib combined with standard of care definitive CRT for HNSCC.
Data from a Phase 3 clinical trial evaluates the efficacy and safety of odronextamab plus CHOP vs rituximab plus CHOP in previously untreated diffuse large B-cell lymphoma (DLBCL) patients. OLYMPIA-3 is a Phase 3, randomized, open-label, multicenter study of O-CHOP vs. R-CHOP in patients with previously untreated DLBCL and intermediate- or high-risk features. The primary endpoints of the study are the incidence of dose-limiting toxicities, and incidence and severity of treatment-emergent adverse events as well as progression-free survival by independent central review.
CIPHER (NCT05333874), a single institution pilot study, evaluated whether trend of circulating tumor DNA (ctDNA) testing during neoadjuvant therapy (NAT) can serve as an early indicator of treatment response and inform disease management in the adjuvant setting. The study included 35 patients with stage II-III triple negative and HER2+ breast cancer and longitudinal ctDNA testing performed during standard of care NAT.
The full list of presentations at this year’s 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting can be found here.

On May 23, 2024 Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a global clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, reported the results from the Phase I/IIa Cohort-G data for Osemitamab (TST001) plus Nivolumab and CAPOX as the first-line treatment of patients with advanced G/GEJ cancer (Press release, Transcenta, MAY 23, 2024, View Source [SID1234643634]). The study, which enrolled patients regardless of their CLDN18.2 and PD-L1 CPS expression, indicated encouraging efficacy data for the triple combination, especially in patients with high or medium (H/M) CLDN18.2 expression, regardless of their PD-L1 CPS value.

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The results showed that median progression-free survival (mPFS) reached 12.6 months in patients with H/M CLDN18.2 expression, any PD-L1 CPS, as well as in the 80% of patients with PD-L1 CPS<5. Using the group of patients with very low/no CLDN18.2 expression as surrogate control, the HR for the triple combination is 0.443 (95%CI, 0.205-0.958) in favor of the H/M expressors and in these patients, the confirmed overall response rate was 68%.

The majority (approximately 80%) of CLDN18.2 positive patients are PD-L1 CPS<5. Previous studies have found that the combination of Zolbetuximab+CAPOX in CLDN18.2 positive patients, regardless of the PD-L1 status, leads to an improvement in PFS from 6.80 to 8.21 months (HR = 0.687 (95% CI, 0.544-0.866) (Source: Shah, Manish A et al. Nature Medicine 2023 Aug 29 (8): 2133-2141). However, Nivolumab plus chemotherapy treatment in patients whose PD-L1 CPS is less than 5 produces very little benefit in PFS (median 7.5 vs 8.2 months with an HR of 0.93). (Source: Checkmate-649 study.) This Phase I/IIa Cohort-G data shows that the efficacy from the triple combo therapy of Osemitamab (TST001) plus Nivolumab and CAPOX compares very favorably with the historical data of Nivolumab plus CAPOX combination or Zolbetuximab plus CAPOX combination, including in patients with PD-L1 CPS<5.

The first-line Osemitamab (TST001) plus Nivolumab and CAPOX for advanced G/GEJ cancer results of Cohort G Phase I/IIa data will be featured as a poster presentation (Abstract # 4048) on June 1, 2024 at the ASCO (Free ASCO Whitepaper) 2024 Annual Meeting in Chicago, IL USA.

"These Phase II results mark a significant milestone for Osemitamab (TST001) as this data continues to demonstrate significant anti-tumor activities, particularly in patients with high or medium CLDN18.2 expression, including in those with PD-L1 CPS<5, which is consistent with our preclinical data and mechanistic hypothesis," said Dr. Caroline Germa, Executive Vice President, Global Medicine Development and Chief Medical Officer at Transcenta. "In this population, the triple combo treatment delivered significantly better PFS benefits than that of the doublet combinations of checkpoint inhibitor/chemo or CLDN18.2 targeted antibody plus chemo. These results further validate our strategy for the Global Phase III trial, which received FDA and CDE clearance and continue to advance the progression of Osemitamab (TST001) toward becoming a global therapy that elevates the current standard of care for HER2-negative metastatic gastric or gastroesophageal (G/GEJ) adenocarcinoma."

"I am excited about these results and the potential they hold for improving the first-line treatment effect and prolonger PFS and OS for patients with HER2-negative metastatic gastric or gastroesophageal (G/GEJ) adenocarcinoma," said Professor Lin Shen, Director, department of Gastrointestinal Oncology and Phase I Clinical Trial Center at Peking University Cancer Hospital; and Principal Investigator of the trial. "We look forward to sharing more detailed data at the upcoming ASCO (Free ASCO Whitepaper) 2024 Annual Meeting."

A brief summary of the study is as follows:

Study Design

Cohort G from TranStar102 study (NCT04495296) was designed to explore the safety and efficacy of Osemitamab (TST001) plus Nivolumab and CAPOX as the first-line treatment in advanced G/ GEJ cancer, with a safety lead-in and expansion phase. Eligible patients include HER2 negative or unknown, unresectable locally advanced or metastatic G/GEJ cancer, regardless of CLDN18.2 or PD-L1 expression. CLDN18.2 and PD-L1 status are analyzed retrospectively using Claudin 18.2 IHC 14G11 LDT assay and PD-L1 IHC 28-8 pharmDx at a central laboratory. The CLDN18.2 expression was divided into three subgroups: H/M (high/medium), L (low) and R (rest: lower or negative) according to the percentage of tumor cells showing membranous CLDN18.2 staining per Claudin 18.2 IHC 14G11 LDT assay.

Encouraging ORR and mPFS

As of the cut-off date, 82 patients had been dosed with a median follow-up of 12.6 months. Efficacy analysis was performed in the 66 patients with known CLDN18.2 and PD-L1 expression status. A clear trend between anti-tumor efficacy and CLDN18.2 expression level has been observed, with mPFS of 12.6 months in the patients with high or medium expression (H/M), 8.5 months in patients with low expression (L) and 6.7 months in the rest patients (R) respectively. Confirmed response rate was respectively 68%, 61.1% and 50% respectively. Compared to the R group, the PFS Hazard Ratio (HR) of HM vs R is 0.443 (95% CI 0.205, 0.985), and HML vs R is 0.560 (95% CI 0.292, 1.074). The same trend was observed in patients with PD-L1 CPS<5 patients, and the mPFS of patients with CLDN18.2 H/M expression is 12.6 months too in this subgroup.

Manageable Safety Profile

The safety profile of the triplet is generally consistent with the safety data of Osemitamab (TST001)/CAPOX combination in 1L G/GEJ cancer patients presented previously (Journal of Clinical Oncology Volume 41, Issue 16, June 1, 2023, Abstract 4046). The main toxicities are on-target-off-tumor effects that are manageable, including nausea, hypoalbuminemia and vomiting, mostly grade 1 or 2.

About Osemitamab (TST001)

Osemitamab (TST001) is a high affinity humanized anti-CLDN18.2 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity ("ADCC"). It has shown potent anti-tumor activities in tumor xenograft models. Osemitamab (TST001) is the second most advanced CLDN18.2 targeting antibody being developed globally. Osemitamab (TST001) was generated using Transcenta’s Immune Tolerance Breaking Technology (IMTB) platform. Osemitamab (TST001) kills CLDN18.2 expressing tumor cells by mechanisms of ADCC. Leveraging advanced bioprocessing technology, the fucose content of Osemitamab (TST001) was significantly reduced during the production, which further enhanced NK cells mediated ADCC activity of Osemitamab (TST001). Clinical trials for Osemitamab (TST001) are ongoing in the U.S. and China (TranStar101/NCT04396821, TranStar102/NCT04495296). Osemitamab (TST001) has been granted Orphan Drug Designation in the U.S. by FDA for the treatment of patients with gastric or gastroesophageal junction (G/GEJ) and pancreatic cancer.