On May 23, 2024 NeraCare, a leading developer of laboratory tests for personalized survival prediction of melanoma patients, reported publication of an abstract describing the clinical validation of a prognostic seven biomarker immunohistochemistry (7-IHC; Immunoprint) risk categorization assay that stratifies patients with early-stage (IB/IIA) cutaneous melanoma into high-risk or low-risk groups for recurrence and melanoma-specific survival, on the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) website (Press release, NeraCare, MAY 23, 2024, View Source [SID1234643659]).

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Results of the Melarisk-001 study demonstrated that use of 7-IHC identified 98% of relapses and 100% of cutaneous melanoma-related deaths in stage IB/IIA patients. Patients with 7-IHC high-risk had a relapse rate comparable to stage IIB-IV patients for whom adjuvant therapy is approved. Results of the study suggest its utility in selecting early-stage melanoma patients for adjuvant trials.

"Anti-PD-1 therapy is a standard of care adjuvant therapy for cutaneous melanoma patients with resected AJCC stages IIB-IV disease." said Jeffrey Weber, MD, PhD, co-author of the poster and Deputy Director of the Perlmutter Cancer Center and Co-Director of the Melanoma Research Center at NYU Langone Health. "Nonetheless, a smaller subgroup of earlier-stage patients with IB or IIA disease is at high risk of relapse and death, and remains without access to adjuvant therapy. This subgroup accounts for a significant share of overall melanoma-related mortality. While adjuvant clinical trials for these earlier-stage patients that will be destined to relapse may be merited, this subgroup is not detectable via current AJCC staging alone. The ability to identify these patients using 7-IHC may be useful in selecting such high-risk participants for adjuvant trials."

The multicenter MELARISK-001 archival study enrolled 382 patients diagnosed with stage IB/IIA cutaneous melanoma with available formalin-fixed paraffin-embedded primary melanoma tissue sections; 247 (65%) patients were categorized as stage IB and 135 (35%) were stage IIA, all sentinel node-negative. Tissue specimens were analyzed by the 7-IHC assay and patients classified as either high-risk or low-risk. The assay measures the expression of five risk markers (Bax, Bcl-X, CD20, COX-2, PTEN) and two protective markers (MTAP, β-Catenin). Median follow-up for recurrence-free survival (RFS) was 90 months and for melanoma-specific survival (MSS), 98 months.

7-IHC classified 212 patients (55%) as high-risk and 170 (45%) as low-risk
7-IHC high-risk patients had significantly worse survival outcomes than 7-IHC low-risk patients
"As the majority of melanoma patients are diagnosed with early-stage disease, there is a critical unmet medical need to identify those at-risk patients to potentially enable earlier access to life-saving therapeutic agents," said Daniel von Janowski, Co-Founder of NeraCare.

"With clinical validation of 7-IHC and the potential for tens of thousands of early-stage melanoma patients to benefit from the test, we are already in the process of transferring the assay from IHC to the Akoya Biosciences’ PhenoImager HT multiplex platform. In doing so, the assay can be fully automated and will require a much smaller tissue sample than is needed for IHC." said Friedrich Ackermann, Co-Founder of NeraCare.

Poster Presentation Details:
Title: Clinical validation of a prognostic 7-marker IHC assay (7-IHC) in 382 patients (pts) with stage IB/IIA cutaneous melanoma (CM; MELARISK-001)
Presenter: Teresa Amaral, MD, PhD, Skin Cancer Center, Department of Dermatology, Eberhard Karls University of Tübingen
Abstract: 9572
Poster Board: 356
Session Title: Melanoma/Skin Cancers
Session Location, Date, and Time: Hall A, Saturday, June 1 – 1:30pm CDT

On May 23, 2024 SOTIO Biotech, a clinical-stage immuno-oncology company owned by PPF Group, reported that it will present on June 1, 2024 (Developmental Therapeutics—Immunotherapy session) a Trial-in-Progress poster on the first-in-human DUET-01 Phase 1/2 study at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, SOTIO, MAY 23, 2024, View Source [SID1234643658]). The study is evaluating the use of BOXR1030, a metabolically enhanced CAR T-cell therapy, for the treatment of patients with solid tumors.

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Patient enrollment and dosing in the DUET-01 clinical trial (NCT05120271) are ongoing at three leading cancer care centers across the U.S., with additional sites expected to be imminently initiated in the U.K.

"The arrival of CAR T-cell therapies has profoundly improved the therapeutic outlook for patients with some blood cancers. Unfortunately, the same has not been true for solid tumors, where cell therapies’ success has been stymied by the challenges of overcoming the tumor microenvironment," said Ecaterina Dumbrava, M.D., Assistant Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center and primary investigator on the DUET-01 trial. "As a metabolically enhanced GPC3-targeting CAR T-cell therapy, BOXR1030 has shown promising preclinical results in resisting tumor microenvironment-like conditions and improving T cell proliferation compared with standard CAR T cells. GPC3 is a clinically validated tumor-restricted target with a high prevalence in several solid tumor indications with unmet medical need. Given these promising observations thus far, we are looking forward to continuing to evaluate its potential in a clinical setting in the DUET-01 study."

The DUET-01 clinical trial is a first-in-human, open-label, multicenter, dose escalation study to assess and determine the recommended Phase 2 dose of BOXR1030 in patients with GPC3-positive advanced solid tumors. The trial will enroll up to 98 patients with advanced, unresectable hepatocellular carcinoma, squamous cell lung cancer, myxoid/round cell liposarcoma, and Merkel cell carcinoma.

Presentation materials will be available on June 1, after presentations conclude, here.

On May 23, 2024 Incendia Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), reported that it will present data in collaboration with PathAI, a leading AI-powered precision pathology company at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 31 – June 4, 2024 in Chicago, Illinois (Press release, Incendia Therapeutics, MAY 23, 2024, View Source [SID1234643657]).

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"I am delighted to be sharing more from our exciting collaboration with PathAI in a poster session at ASCO (Free ASCO Whitepaper), highlighting the potential of utilizing digital pathology-based biomarkers to predict outcome in a clinical setting," said Laura Dillon, PhD, Vice President of Translational Medicine & Bioinformatics at Incendia Therapeutics. "The data demonstrate the correlation between immune phenotypes predicted from hematoxylin and eosin (H&E)-stained whole slide images and survival following checkpoint inhibitor therapy in non-small cell lung cancer (NSCLC). We believe these data support the possibility of improving patient outcomes in NSCLC by advancing the identification of PD-L1(-) patients who may derive greater benefit from treatment with check-point inhibitors."

Presentation details for ASCO (Free ASCO Whitepaper) 2024 are as follows:

Title: Correlation of immune phenotypes derived from H&E-stained whole slide images with prognosis and response to checkpoint inhibitors in NSCLC
Abstract Number: 8539
Presenting Authors: Bahar Rahsepar, Senior AI Product Manager at PathAI, Inc. and Laura Dillon, Ph.D., Vice President of Translational Medicine & Bioinformatics at Incendia Therapeutics
Poster Session: Lung Cancer—Non-Small Cell Metastatic
Date and Time: Monday, June 3 from 1:30 – 4:30 PM CDT (2:30 – 5:30 PM EDT)

Key Highlights:

The classification of tumors as inflamed, excluded or desert based on spatial patterns of tumor infiltrating lymphocytes (TILs) is a potential biomarker of patients likely to respond to checkpoint inhibitors (CPI). However, the subjectivity of manual methods to assess these immune phenotypes (IPs) and poor standardization in the methods and thresholds to define IPs have hampered their clinical adoption. Using a data-driven approach for predicting IPs using patch-level TIL features, AI model-predicted IPs were prognostic in The Cancer Genome Atlas (TCGA) NSCLC dataset and predictive of progression free survival (PFS) in a CPI- treated clinical NSCLC cohort. Association of IP and PFS was independent of PD-L1 status, potentially allowing the identification of PD-L1(-) patients who may derive greater benefit from CPI.

In The Cancer Genome Atlas (TCGA) NSCLC cohort, model-predicted inflamed immune phenotypes (IP) (iIP) (N=196) and excluded IP (eIP) (N=607) patients had significantly better overall survival (OS) compared to desert IP (dIP) (N=80; HR=0.53, p=0.003 and HR=0.59, p=0.003, respectively). In the clinical cohort, cancer tumor infiltrating lymphocytes density and fraction of hot epithelial patches were significantly associated with (PFS) (HR=0.64, q=0.04 and HR=0.69, q=0.04, respectively). PFS was significantly shorter in model-predicted eIP patients (N=46) compared to iIP (N=39; HR=0.54, p=0.045). Notably, in PD-L1(-) patients (N=43, tumor proportion score ≤1%), iIP patients had longer PFS than eIP and dIP patients (HR=0.35, p=0.02). No difference in PFS was observed for PD-L1(+) patients.

On May 23, 2024 AffyImmune Therapeutics, a clinical-stage biotechnology company committed to developing novel, first-in-class CAR T cell therapies, reported early results from a Phase 1 study evaluating the safety and efficacy of AIC100, an ICAM-1 targeting and affinity-tuned LFA-1 binder chimeric antigen receptor (CAR) T-cell therapy, in patients with advanced thyroid cancer (Press release, AffyImmune Therapeutics, MAY 23, 2024, View Source [SID1234643656]). Notably, a metabolic complete response (mCR) was achieved in one patient with anaplastic thyroid cancer (ATC), the most aggressive form of the disease.

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"We are excited to be the first to demonstrate the potential of autologous CAR T to induce a complete response in a patient with a solid tumor cancer. The confirmed mCR in the AIC100 Phase 1 study is the first known complete response following a single IV dose of autologous CAR T cells observed in any solid tumor cancer type," said Matt Britz, CEO, AffyImmune.

"This Phase 1 study addresses the urgent unmet medical need for effective treatments for patients with advanced differentiated thyroid cancer (ADTC) and ATC which has a median survival rate of less than six months. These are aggressive forms of thyroid cancer that currently have limited treatment options and poor patient outcomes. We believe AIC100 has the potential to overcome current barriers to CAR T, and ultimately establish a new paradigm for patients with solid tumor cancers," Britz added.

As of the data cutoff date, 10 patients (6 ATC; 4 PDTC) were infused with AIC100 at 3 dose levels (DLs). No dose-limiting toxicities were observed across all dose levels, and the maximum tolerated dose was not reached. 60% (n=6) of patients developed grade 1/2 cytokine release syndrome (CRS), with no incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) or other serious adverse events related to AIC100.

For evaluable patients in DL2 (100 million CAR T cells) and DL3 (500 million CAR T cells) (n=6), the ORR was 33%, with one patient at DL2 achieving a durable partial response (PR) and another patient at DL3 achieving an ongoing durable mCR allowing the patient to be off all chemotherapy. DCR was 67%.

"These findings represent a significant milestone in the development of AIC100 as a potential treatment option for patients with advanced thyroid cancers. The safety profile and promising antitumor activity observed in this Phase 1 study provide a strong foundation to advance this candidate further in development," said Dr. Samer A. Srour, the trial’s Lead Investigator and Assistant Professor at The University of Texas MD Anderson Cancer Center. "We look forward to improve on these results and to further evaluate the safety and efficacy of AIC100 at higher dose levels and to potentially expand its application to other ICAM-1-positive cancers."

Presentation Details:

Title: Safety and Efficacy of AIC100 Chimeric Antigen Receptor (CAR) T-cell Therapy in Patients with Advanced Thyroid Cancers: results from the phase 1 study

Presenter: Dr. Samer Ali Srour, The University of Texas MD Anderson Cancer Center

Session Type: Poster Session– Head and Neck Cancer

Abstract Number: 6112

Date and Time: June 2, 2024: 9:00 AM – 12:00 PM CDT

Location: McCormick Place Convention Center, Chicago, IL

AffyImmune will also be hosting an event during ASCO (Free ASCO Whitepaper) 2024:

Event: Navigating Advanced Thyroid Cancer: Unmet Needs and Innovations

Date and Time: Monday, June 3, 2024 / 6:00 – 7:00 PM

Location: Hyatt Regency McCormick Place, Chicago, IL

RSVP: View Source

For more information about the Phase 1 study, visit www.clinicaltrials.gov (NCT04420754).

On May 23, 2024 The Menarini Group ("Menarini"), a leading international pharmaceutical and diagnostics company, and Stemline Therapeutics, Inc. ("Stemline"), a wholly-owned subsidiary of the Menarini Group, focused on bringing transformational oncology treatments to cancer patients, reported that it will present updated results from phase 1b/2 ELECTRA and ELEVATE clinical studies evaluating elacestrant (ORSERDU) in combination with other treatments (Press release, Menarini, MAY 23, 2024, View Source;Metastatic-Breast-Cancer-mBC-at-the-ASCO-2024-Annual-Meeting [SID1234643655]). Both the ELECTRA and ELEVATE studies were designed to overcome different resistance mechanisms observed in estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC) and improve patient outcomes through novel oral-oral combination treatment options. Data will be presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), on June 2 from 9 a.m. to 12 p.m. CT.

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The ELECTRA study is evaluating elacestrant in combination with abemaciclib in patients with ER+, HER2- metastatic breast cancer with brain metastases; however, the phase 1b portion of this study was conducted in all metastatic sites, including brain metastases. The updated phase 1b results continue to show a satisfactory safety profile, consistent with prior findings, and promising activity in patients with ER+, HER2- advanced or mBC regardless of metastatic site. Based on the results of this portion of the study, the recommended phase 2 dose (RP2D) will be reported as part of the data presentation. Currently, the phase 2 portion of ELECTRA is ongoing at the RP2D to further characterize the efficacy and safety in patients with ER+, HER2- metastatic breast cancer with brain metastases, since both elacestrant and abemaciclib cross the blood-brain barrier.

"It is encouraging to see that, even in the early stages of the trial, the combination of elacestrant plus abemaciclib indicates a tolerable and manageable safety profile for the patients in the clinical trial," said Erika Hamilton, MD, Director of Breast Cancer Research and Executive Chair of the Breast Cancer Research Executive Committee for Sarah Cannon Research Institute. "The study continues to demonstrate elacestrant’s potential in combination with other therapies and we look forward to analyzing more data from this combination for this patient population in need of new options."

The ELEVATE study is evaluating elacestrant in combination with CDK4/6 inhibitors (palbociclib, abemaciclib and ribociclib) and with inhibitors of the PI3K/AKT/mTOR pathway (everolimus, alpelisib and capivasertib). The updated Phase 1b results show that the combinations evaluated are consistent with the known safety profiles of each targeted therapy plus standard of care endocrine therapy. Based on the results of this portion of the study, the RP2D will be reported for elacestrant in combination with everolimus. Additional cohorts, including elacestrant plus capivasertib, are currently under evaluation to further characterize the safety, assess efficacy and determine the RP2D for each combination arm. Phase 2 for the combination of elacestrant and abemaciclib in ER+, HER2- metastatic breast cancer, irrespective of the metastatic site, is already ongoing.

"As we evaluate the various combinations of elacestrant plus CDK4/6 and PI3K/AKT/mTOR inhibitors, we continue to see consistent and manageable safety findings across all arms of the trial, and so far, elacestrant does not appear to add any incremental toxicity to the combination regimens in which it is being studied," Hope S. Rugo, MD, Professor of Medicine and Winterhof Family Endowed Professor in Breast Cancer, Director, Breast Oncology and Clinical Trials Education, University of California San Francisco. "These data build on our understanding of elacestrant’s role in metastatic breast cancer and reinforce its potential as an endocrine therapy backbone in combination regimens."

"Since its approval in 2023, ORSERDU has had a meaningful impact as an endocrine therapy for people who are living with ER+, HER2- metastatic breast cancer harboring ESR1 mutations," said Elcin Barker Ergun, CEO of the Menarini Group. "The data we are presenting at ASCO (Free ASCO Whitepaper) highlight elacestrant’s potential to further enhance patient outcomes when combined with other compounds."

About The Elacestrant Clinical Development Program

Elacestrant is also being investigated in several company-sponsored clinical trials in metastatic breast cancer disease, alone or in combination with other therapies. ELEVATE (NCT05563220) is a phase 1b/2 clinical trial evaluating the safety and efficacy of elacestrant combined with alpelisib, everolimus, capivasertib, palbociclib, ribociclib or abemaciclib. ELECTRA (NCT05386108) is an open-label phase 1b/2, multicenter study evaluating elacestrant in combination with abemaciclib in patients with ER+, HER2- breast cancer. The phase 2 portion evaluates this treatment regimen in patients with brain metastases. ELCIN (NCT05596409) is a phase 2 trial evaluating the efficacy of elacestrant in patients with ER+, HER2- advanced/metastatic breast cancer who received one or two prior hormonal therapies and no prior CDK4/6 inhibitors in the metastatic setting. ADELA (NCT06382948) is a phase 3 randomized, double-blinded trial evaluating elacestrant in combination with everolimus in patients with ER+, HER2- mBC with ESR1-mut tumors. Elacestrant is also being evaluated in additional investigator-led trials, in trials conducted in collaboration with other companies, in metastatic breast cancer as well as in early disease.

About ORSERDU (elacestrant)

U.S. Indication: ORSERDU (elacestrant), 345 mg tablets, is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

Full prescribing information for the U.S. can be found at www.orserdu.com.

Important Safety Information

Warning and Precautions

Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid profile prior to starting and periodically while taking ORSERDU.

Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the final dose.

Adverse Reactions

Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each).

The most common adverse reactions (>10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite(15%), diarrhea(13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%).

Drug interactions

Concomitant use with CYP3A4 Inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU.

Use in specific populations

Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose.

Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B).

The safety and effectiveness of ORSERDU in pediatric patients have not been established.

To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.