On May 25, 2023 AffyImmune Therapeutics, Inc., a clinical stage biotechnology company finding safe, effective ways to use CAR T cells against solid cancers, reported positive safety and early efficacy results from a Phase 1 study of affinity tuned and trackable AIC100 CAR T cells in ICAM-1 positive relapsed and/or refractory advanced poorly differentiated and anaplastic thyroid cancers, which will be presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois, on June 5, 2023 (Press release, AffyImmune Therapeutics, MAY 25, 2023, View Source [SID1234632109]).

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"We are very encouraged by the early data, as it marks a groundbreaking CAR T patient response in aggressive and difficult to treat anaplastic thyroid cancers," said Matt Britz, Chief Operating Officer at AffyImmune. "This is an important clinical milestone for AffyImmune as we continue to develop AIC100 in the clinic and explore additional solid tumor indications with high unmet need."

The current Phase 1 study is exploring three dose levels (DL) of AIC100 CAR T cells, which are developed using AffyImmune’s proprietary Tune & Track CAR T cell platform. To date, AIC100 CAR T cells demonstrated excellent safety and encouraging efficacy in anaplastic (ATC) and poorly differentiated (PDTC) thyroid cancers.

As of May 1, 2023, seven patients (4 ATC; 3 PDTC) were infused with AIC100: three patients (2 ATC, 1 PDTC) in DL1 and four patients (2 ATC, 2 PDTC) in DL2. Early results from the Phase 1 study include:

No DLTs were reported; two patients had transient grade 1 CRS.
For the four patients infused in DL2, two patients were evaluable for efficacy assessment at day 42. Both had tumor reductions. One ATC patient achieved partial response (PR) with 42 percent reduction in target tumor lesion and a second PDTC patient had stable disease (SD).
"The objective partial response in DL2 for a patient with metastatic ATC who failed multiple lines of therapy is unprecedented and very encouraging," said Samer Ali Srour, MB ChB, MS, assistant professor of Stem Cell Transplantation & Cellular Therapy at The University of Texas MD Anderson Cancer Center. "AIC100 demonstrated an excellent safety profile with no DLTs in patients with ATC and PDTC, and the antitumor activity is promising, especially these responses were observed at the low dose levels 1 and 2."

Details of the poster presentation:

Abstract Title: Safety and early efficacy results of phase 1 study of affinity tuned and trackable AIC100 CAR T cells in ICAM-1 positive relapsed and/or refractory advanced poorly differentiated and anaplastic thyroid cancers

Session Title: Head and Neck Cancer

Date and Time: Monday, June 5, 1:15 PM-4:15 PM CDT

Location: McCormick Place Convention Center, Exhibit Hall A, Poster Board 87

Presenter: Samer Ali Srour, MBChB, MS, Assistant Professor, Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

On May 25, 2023 Servier, a leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported that it will showcase new data across its robust oncology portfolio at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting June 2-6, 2023 (Press release, Servier, MAY 25, 2023, View Source [SID1234632108]). These latest data, including a plenary session selection, underscore the breadth of Servier’s oncology pipeline and portfolio and the company’s commitment to improving outcomes for difficult and hard-to-treat cancers with high unmet medical needs.

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Among the data to be presented is a late breaking abstract featuring the results from the Phase 3 INDIGO study of vorasidenib in patients with residual or recurrent grade 2 IDH-mutant glioma. These data represent the first study to show clinically meaningful and statistically significant improvements in low-grade glioma in 23 years and was accepted as one of only four presentations for a plenary session to take place on June 4, 2023 from 1:00 – 4:00 p.m. C.T.

"Servier is leading the scientific research with IDH inhibition across a variety of difficult to treat cancers, and this year at ASCO (Free ASCO Whitepaper), we are excited to showcase data that has the potential to shift the treatment paradigm for patients with IDH-mutant glioma," said Susan Pandya, M.D., Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier. "IDH mutations are recognized as drivers of disease biology in patients with a broad range of cancers, including glioma, and the distinguishing selection of the Phase 3 INDIGO trial for a plenary session is a testament to the groundbreaking research that is yielding long-awaited progress for glioma patients."

Additional research to be presented includes:

Long-term follow up data, including updated overall survival, from the Phase 3 AGILE study of TIBSOVO (ivosidenib) plus azacitidine in patients with previously untreated IDH1-mutant acute myeloid leukemia (AML) who are not eligible to receive intensive chemotherapy.
Long-term follow-up data for TIBSOVO monotherapy in patients with IDH1-mutant conventional chondrosarcoma, a rare bone malignancy for which there are no approved systemic therapies
Clinical and molecular characteristics for patients with relapsed/refractory IDH1-mutant AML with an exceptional response to TIBSOVO
Data from across Servier’s global colorectal cancer (CRC) research
"Through a persistent focus on smart science, we are coming into ASCO (Free ASCO Whitepaper) with incredible momentum and exciting data from across our diversified portfolio," said Philippe Gonnard, M.D., Executive Vice President, Global Product Strategy at Servier. "Building off the recent European Commission approval for TIBSOVO in certain patients with acute myeloid leukemia (AML) and cholangiocarcinoma, we look forward to showcasing updated overall survival for TIBSOVO in patients with AML, as well as sharing the positive results from our Phase 3 INDIGO study of vorasidenib in residual/recurrent grade 2 IDH-mutant diffuse glioma – marking the first major advancement in low-grade glioma in more than two decades and cementing our leadership in IDH inhibition."

Servier abstracts being presented at ASCO (Free ASCO Whitepaper) are listed below (all times in Central Time) and are available online on the ASCO (Free ASCO Whitepaper) website here.

Abstract LBA1: A Phase 3 global, randomized, double-blinded placebo-controlled study of vorasidenib in patients with residual or recurrent grade 2 glioma with an isocitrate dehydrogenase 1/2 (IDH1/2) mutation

Date & Time: Sunday, June 4, 1:00 – 4:00 p.m.
Lead Author: Ingo K. Mellinghoff
Abstract #7012: Updated efficacy and safety data from the AGILE study in patients with newly-diagnosed acute myeloid leukemia treated with ivosidenib + azacitidine compared to placebo + azacitidine

Date & Time: Monday, June 5, 12:30 p.m. – 2:00 p.m.
Lead Author: Stephane de Botton
Abstract #11532: Phase I study of the mutant IDH1 inhibitor ivosidenib: long-term safety and clinical activity in patients with conventional chondrosarcoma

Date & Time: Saturday, June 3, 2:15 – 5:15 p.m.
Lead Author: William D. Tap
Abstract #7036: Clinical and molecular characteristics of AML patients with an exceptional response to ivosidenib

Date & Time: Monday, June 5, 9:00 a.m. – 12:00 p.m.
Lead Author: Justin Watts
Abstract #3512: Overall survival results for trifluridine/tipiracil plus bevacizumab vs capecitabine plus bevacizumab: results from the phase 3 SOLSTICE study

Date & Time: Monday, June 5, 2:15 – 3:45 p.m.
Lead Author: Thierry Andre
Abstract #3594: Effect of trifluridine/tipiracil in combination with bevacizumab on ECOG-PS in refractory metastatic colorectal cancer: An analysis of the phase 3 SUNLIGHT trial

Date & Time: Monday, June 5, 9:00 a.m. – 12:00 p.m.
Lead Author: Julien Taieb
Abstract #3556: Trifluridine/tipiracil (FTD/TPI) in extensively pre-treated metastatic colorectal cancer (mCRC) patients – Evaluation of prognostic subgroups of the TALLISUR study

Date & Time: Monday, June 5, 9:00 a.m. – 12:00 p.m.
Lead Author: M. Karthaus
Abstract #3580 Phase II trial of trifluridine/tipiracil (TAS102) and nanoliposomal irinotecan (nal-IRI) in advanced colorectal cancer (CRC)

Date & Time: Monday, June 5, 9:00 a.m. – 12:00 p.m.
Lead Author: O.B. Alese
Additionally, at the European Hematology Association (EHA) (Free EHA Whitepaper) annual meeting in Frankfurt, Germany, June 8-11, 2023 Servier will present four posters, including updated substudy results for ivosidenib in IDH1-mutant relapsed/refractory myelodysplastic syndrome (MDS). Servier abstracts being presented at EHA (Free EHA Whitepaper) are listed below (all times in Central European Summer Time) and are available online on the EHA (Free EHA Whitepaper) website here.

Abstract #P490: Updated efficacy and safety data from the AGILE study in patients with newly-diagnosed acute myeloid leukemia treated with ivosidenib + azacitidine compared to placebo + azacitidine

Date & Time: Friday, June 9, 6:00 – 7:00 p.m.
Session: Acute myeloid leukemia – Clinical
Lead Author: Stephane de Botton
Abstract #P441: Clinical and molecular characteristics of AML patients with an exceptional response to ivosidenib

Date & Time: Friday, June 9, 6:00 – 7:00 p.m.
Session: Gene therapy and immunotherapy – Biology & translational research
Lead Author: Justin Watts
Abstract #P724: Updated substudy results for ivosidenib in IDH1-mutant relapsed/refractory myelodysplastic syndrome

Date & Time: Friday, June 9, 6:00 – 7:00 p.m.
Session: Myelodysplastic syndromes – Clinical
Lead Author: Courtney DiNardo
Abstract #P386: Comparison of the pharmacokinetics of the liquid and lyophilized formulations of pegaspargase in the treatment of pediatric patients with acute lymphoblastic leukemia (ALL)

Date & Time: Friday, June 9, 6:00 – 7:00 p.m.
Session: Acute lymphoblastic leukemia – Clinical
Lead Author: A.I. Karachunskiy

On May 25, 2023 OncoHost, a technology company transforming the approach to precision medicine for improved patient outcomes, reported that it will give a poster presentation demonstrating the accuracy of its PROphet biomarker model at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 2-6, 2023, in Chicago, Illinois (Press release, OncoHost, MAY 25, 2023, View Source [SID1234632106]).

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Initial treatment selection for advanced non-small cell lung cancer (NSCLC) patients without driver mutations is primarily based on evaluating PD-L1 expression levels in the tumor tissue. However, PD-L1 assays are only moderately predictive. In addition, guidelines for the PD-L1 ≥50% subpopulation are not definitive, enabling the use of immune checkpoint inhibitors (ICIs) either as monotherapy, or combined with chemotherapy.

OncoHost’s proprietary platform, PROphet, is a plasma-based, proteomic pattern analysis tool whose initial offering in NSCLC uses a single blood sample to guide first-line immunotherapy decision-making. The PROphet algorithm is trained on OncoHost’s large-scale clinical trial, PROPHETIC. To date, the trial has over 1,700 patients recruited across 40 sites worldwide, making it one of the largest prospective cohorts in the precision oncology field.

"Our goal is to provide a decision-making tool for the first-line treatment of advanced NSCLC patients based on plasma-derived biomarkers obtained before treatment initiation," said Itamar Sela, Ph.D., VP R&D at OncoHost and lead author of the study. "Our PROphet model continues to display strong performance, with a high correlation between the predicted clinical benefit and the observed clinical benefit rate, outperforming the current PD-L1-based prediction model. We’re excited to present this accurate alternative to improve the lives of patients."

The researchers examined the clinical utility of combining the PROphet output with PD-L1 levels by comparing different treatment modalities and concluded that the model output complements tissue PD-L1 expression levels as a tool to assist therapeutic decisions. Essentially, plasma proteomic profiling can provide biomarkers that accurately predict the benefit of ICI-based treatment for advanced, unresectable cancer patients.

"Traditional precision medicine searches for biomarkers at the therapy-tumor axis. By adding the patient to the equation, we’re fighting cancer through a unique, deep profiling of the patient-tumor interface," said Dr. Ofer Sharon, CEO of OncoHost. "Our ongoing research demonstrates the clear clinical utility of our PROphet platform, offering targeted treatment options for patients and identifying previously unanticipated targets for future interventions and clinical trials. This is a crucial time for precision oncology."

The clinical study was conducted in collaboration with Heidelberg University’s BioMaterialBank, Roswell Park Comprehensive Cancer Center, Thomas Jefferson University, Chaim Sheba Medical Center Institute of Oncology, UC Davis Comprehensive Cancer Center, OSUCCC – James – The Ohio State University, Asklepios Lung Clinic, Hadassah Cancer Research Center and Rambam Health Care Campus.

Poster Presentation Details
Session: Lung Cancer—Non-Small Cell Metastatic
Abstract #: 9122
Poster Bd #: 110
Title: A decision-making tool for first-line treatment in advanced non–small-cell lung cancer based on plasma proteome biomarkers.
Presenter: Itamar Sela, Ph.D., VP R&D at OncoHost
Date/Time: Tuesday, June 4, 2023, 8:00 AM-11:00 AM

On May 25, 2023 I-Mab (the "Company") (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of novel biologics, reported encouraging results from the Phase 1b/2 study (ClinialTrial.gov Identifier: NCT04322006) evaluating uliledlimab, the Company’s proprietary and highly differentiated CD73 antibody, in combination with toripalimab (TUOYI), a PD-1 antibody, in patients with treatment-naïve advanced non-small cell lung cancer (NSCLC), and exploring the potential value of CD73 expression as a predictive biomarker (Press release, I-Mab Biopharma, MAY 25, 2023, View Source [SID1234632105]). The results will be reported in a poster presentation on June 3 at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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The study is a dose expansion portion of a Phase 1b/2 trial evaluating the safety and efficacy of the combination therapy and investigating the potential correlation between tumor CD73 expression and clinical response for patients with treatment-naïve advanced NSCLC.

As of April 14, 2023, a total of 70 patients were enrolled in the study. Uliledlimab demonstrated a favorable safety profile up to 30mg/kg Q3W in combination with toripalimab with most treatment-related adverse events (TRAEs) being Grade 1 or Grade 2 in severity. In the efficacy evaluable population (n=67), the objective response rate (ORR) was 31.3% regardless of PD-L1 and CD73 expression. CD73High was established as >40% of tumor or immune cells with ≥1+ staining intensity identified by immunohistochemistry (IHC). The cutoff was determined through receiver operating characteristic (ROC) analysis.

Notably, patients with CD73High exhibited a higher ORR compared with those with CD73Low (53% vs. 18%). The ORR further increased to 63% in patients with both CD73High and PD-L1 tumor proportion score (TPS)≥1%, whereas patients with CD73Low had an ORR of 20%. At the time of data cutoff, with a median follow-up of 10.4 months, 18 out of 21 responders remained on treatment, and the median duration of response (DOR) was not reached. Progression-free survival (PFS) and overall survival (OS) data will be analyzed when the data are fully mature.

"These results hold promise for the treatment of NSCLC patients, as demonstrated by the favorable safety and efficacy outcomes," said Professor Yi-Long Wu, Principal Investigator of the study and Professor of Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences and Guangdong Lung Cancer Institute. "We are particularly excited about the potential of CD73 expression as a predictive biomarker, which is consistent with findings in our previous studies. The results may transform how we personalize NSCLC treatment through stratification by a predictive biomarker."

"The new results are compelling for uliledlimab as a new treatment for NSCLC and its potential to make a meaningful impact on patients’ lives. We’re particularly excited by the strong correlation between high CD73 expression and clinical response. With this finding, we are in a unique position to apply CD73 as a predictive biomarker to raise the probability of treatment success for NSCLC," said Dr. Andrew Zhu, President and Acting CEO of I-Mab. "Building on encouraging results from this study, we intend to commence a biomarker-guided pivotal trial with the aim of providing these promising new treatment options to patients as quickly as we can."

These data will be reported in a poster presentation, entitled Uliledlimab and Toripalimab Combination Therapy in Treatment Naïve Advanced NSCLC: Phase 1b/2 Clinical Trial Results Using CD73 as a Potential Predictive Biomarker (Abstract #2570), at ASCO (Free ASCO Whitepaper) on June 3, 2023, from 8:00 a.m. – 11:00 a.m. C.T. by Dr. Qing Zhou, Professor of Guangdong Provincial People’s Hospital.

About Uliledlimab

Uliledlimab (also known as TJD5) is a differentiated, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine. Adenosine, in turn, binds to adenosine receptors on relevant immune cells and inhibits anti-tumor immune responses in the tumor microenvironment. Uliledlimab is expected to offer clinical benefits by suppressing tumor growth in concert with checkpoint therapies such as PD-(L)1 antibodies. Uliledlimab is effective in anti-tumor activities through a unique intra-dimer binding, leading to differentiated and favorable functional properties, as evident in preclinical studies.

On May 25, 2023 Biotheryx, Inc., a biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders with a focus on validated targets in cancer and inflammatory disease, reported two poster presentations at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held June 2–6, 2023, in Chicago, Illinois and online (Press release, BioTheryX, MAY 25, 2023, View Source [SID1234632104]). The presentations highlight preclinical data for bifunctional degraders of CDK4/6, including development candidate BTX-9341, for the treatment of estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-), and of son of sevenless homolog 1 (SOS1) for the treatment of KRAS mutant cancers.

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"These new preclinical data demonstrate the potential of our bifunctional CDK4/6 and SOS1 degraders to potently degrade their targets, ultimately effectively inhibiting tumor growth together with the strength of Biotheryx’s PRODEGY platform to efficiently design first-in-class degraders," said Philippe Drouet, President and Chief Executive Officer of Biotheryx. "Besides these encouraging efficacy results, BTX-9341, our oral CDK4/6 development candidate, exhibited superior blood brain barrier penetration versus inhibitors and good tumor exposure when dosed orally. We look forward to advancing BTX-9341 towards clinical development to overcome drug resistance challenges faced by patients with solid tumors such as ER+/HER2- breast cancer."

2023 ASCO (Free ASCO Whitepaper) Annual Meeting Presentation Details:

Title: Discovery of CDK4/6 bifunctional degraders for ER+/HER2- breast cancer and triple negative breast cancer
Presenter: Hannah Majeski, Ph.D., Principal Scientist – Biology
Abstract #: 1083
Session: Breast Cancer – Metastatic
Session Date and Time: Sunday, June 4, 2023, at 8:00 a.m. CDT
Highlights:

CDK4/6 inhibitors are used to treat ER+/ HER2- breast cancer, but some patients have exhibited innate resistance, and many are shown to develop acquired resistance after three years on therapy.
BTX-9341, discovered and developed by Biotheryx’s proprietary PRODEGY platform, is a potent, Cereblon- and proteasome-dependent degrader of CDK4 and CDK6 in multiple breast cancer cell lines.
BTX-9341 demonstrated in vitro CDK4 and CDK6 degradation in multiple breast cancer cell lines and potent inhibition of cell proliferation. This potency was shown to be superior to CDK4/6 inhibitors, due to Cereblon-mediated target degradation.
The CDK4/6 bifunctional degraders were active in a CDK4/6 inhibitor resistant cell line and in multiple PDX CDK4/6 inhibitor resistant organoid models.
BTX-9341 exhibited good tumor exposure when dosed orally, and induced a dose-dependent reduction in CDK4, CDK6 and pRB levels in MCF7 xenograft tumors. This resulted in dose dependent tumor growth inhibition, tumor regression and superior efficacy compared to CDK4/6 inhibitors.
BTX-9341 and its analogue bifunctional degraders have also shown blood brain barrier penetration and superior inhibition of tumor growth in an MCF7 intracranial mouse model compared to a CDK4/6 inhibitor.
The combination of the enhanced efficacy, activity in CDK4/6 inhibitor resistant models and blood brain barrier penetration demonstrate the potential for CDK4/6 degraders in a range of potential cancer indications.
Title: Development of bifunctional CRBN-SOS1 degraders for treatment of mutant KRAS cancers
Presenter: Kyle Begovich, Ph.D., Senior Scientist – Biology
Abstract #: 3151
Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Session Date and Time: Saturday, June 3, 2023, at 8:00 a.m. CDT
Highlights:

KRAS is the most frequently mutated cancer-causing oncogene and is mutated in over 20% of all human cancers, including an estimated 90% of pancreatic cancer, 45% of colorectal cancer and 30% of lung cancer. Combination therapeutic approaches are likely needed to avoid drug resistance in the treatment of KRAS mutant cancers, such as coupling KRAS inhibition with a blockade of its guanine exchange factor (GEF), SOS1, to keep KRAS in its inactive state as well as prevent upstream pathway reactivation.
Biotheryx’s SOS1 bifunctional degraders demonstrated antiproliferative effects across a range of KRAS-mutant cell lines. Treatment with SOS1 degraders in KRAS-mutant xenograft models resulted in greater than 90% degradation of SOS1 in tumors and subsequently led to significant tumor growth inhibition as a single agent.
SOS1 degraders also exhibited synergistic effects with other RAS/MAPK pathway inhibitors, such as KRAS G12C, KRASG12D, EGFR and MEK inhibitors in in vitro studies as well as in KRAS-mutant xenograft models.
These data support the potential of SOS1 degradation as a valuable treatment option for a range of KRAS mutant cancers, as a monotherapy and in combination with other RAS-MAPK pathway inhibitors.
Following the presentations at the meeting, PDF copies of the presentations and posters will be available in the "Publications and Presentations" section of Biotheryx’s website.