On May 20, 2021 Ribon Therapeutics, a clinical stage biotechnology company developing therapeutics targeting stress support pathways, reported that data from its first-in-human Phase 1 trial evaluating RBN-2397, its small molecule inhibitor of PARP7, as a monotherapy in patients with advanced solid tumors was selected for an oral presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Ribon Therapeutics, MAY 20, 2021, View Source [SID1234580389]). Presenting the data will be Gerald S. Falchook, M.D., Director, Drug Development, Sarah Cannon Research Institute at HealthONE, Denver, CO and Clinical Investigator in the RBN-2397 Phase 1 trial. The full meeting program is available at: www.asco.org.

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"The data being presented at ASCO (Free ASCO Whitepaper) emphasizes the therapeutic potential of RBN-2397 as a novel inhibitor of PARP7 which aims to restore Type I interferon signaling in tumors and antitumor immunity. Our distinctive approach of targeting stress support pathways is a promising novel strategy for treating multiple types of cancer," said Victoria Richon, Ph.D., President and Chief Executive Officer, Ribon Therapeutics. "We are encouraged that the data being shared show that RBN-2397 has been well tolerated with evidence of target engagement in the dose escalation portion of our Phase 1 trial and we look forward to providing future updates as the program advances in the clinic."

The data will be presented as follows:

Abstract Title: A first-in-human phase 1 study of a novel PARP7 inhibitor RBN-2397 in patients with advanced solid tumors
Session Date & Time: Friday, June 4, 2021 at 11:00 a.m. ET
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Presenter: Gerald S. Falchook, M.D., Director, Drug Development, Sarah Cannon Research Institute at HealthONE, Denver, CO and Clinical Investigator in the RBN-2397 Phase 1 trial
Abstract ID: 3000
Summary:

Targeting cytosolic nucleic acid sensing pathways and the Type I interferon (IFN) response is an emerging therapeutic strategy in oncology. PARP7 is a member of the monoPARP class of enzymes and a newly identified negative regulator of nucleic acid sensing in tumor cells. PARP7 expression is increased by cellular stress and aromatic hydrocarbons, and the PARP7 gene is amplified in multiple cancers. RBN-2397 is a potent, selective inhibitor of PARP7. To date, RBN-2397 is well tolerated and demonstrates dose dependent increases in plasma exposures, evidence of target inhibition and preliminary signs of clinical activity.
About RBN-2397
RBN-2397 is an orally available small molecule inhibitor of PARP7 that Ribon Therapeutics is developing for the treatment of solid tumors. PARP7 is upregulated in response to cellular stress, including genomic instability in cancers, and acts as a brake on the cellular stress response by negatively regulating the Type I interferon response. By inhibiting PARP7 in tumor cells, RBN-2397 has been shown to directly inhibit cellular proliferation and restore interferon signaling to stimulate an innate and adaptive antitumor immune response. RBN-2397 is currently in a Phase 1 clinical trial as a monotherapy in patients with advanced solid tumors (NCT04053673). PARP7 is overexpressed in a number of tumors, including squamous cell carcinoma of the lung, or SCCL, which represents approximately 30% of all non-small cell lung cancers.

On May 20, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a dermatologic diagnostics company providing personalized genomic information to inform treatment decisions, reported a publication describing the findings of a squamous cell carcinoma (SCC) gene expression profiling (GEP) expert panel in the Journal of Drugs in Dermatology (Press release, Castle Biosciences, MAY 20, 2021, View Source [SID1234580388]). The publication provides a framework for integrating DecisionDx-SCC into clinical practice.

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Treatment plan decisions in SCC are based upon the likelihood of an individual patient’s tumor to metastasize. Data from previous studies has demonstrated that DecisionDx-SCC, Castle’s prognostic 40-GEP test designed to use a patient’s tumor biology to predict individual risk of metastasis for patients with SCC and one or more risk factors, is a significant, independent predictor of risk, compared to existing traditional clinical and pathologic staging systems.

The article, titled "Clinical Considerations for Integrating Gene Expression Profiling into Cutaneous Squamous Cell Carcinoma Management," describes the findings of a multidisciplinary expert panel, representing backgrounds from academic medical centers and community practices. The panel also included specialties clinicians, such as Mohs surgeons, surgical oncologists and a radiation oncologist. The panel reviewed traditional risk assessment practices, guidelines and expert recommendations on DecisionDx-SCC. The panel also focused on decision-making points, where information from DecisionDx-SCC might inform the clinical management of patients with SCC and one or more risk factors.

Study findings:

Decision points supported by DecisionDx-SCC test results include:
nodal evaluation
adjuvant radiation therapy
follow-up and surveillance
The panel determined that the additional information provided by DecisionDx-SCC could:
help avoid unnecessary treatment and surveillance
allow healthcare providers to increase treatment intensity or follow-up as needed
inform if and when to refer a patient for medical, surgical, or radiation oncology
"This is an exciting time in the management of high-risk squamous cell carcinoma patients," said study author, Sherrif Ibrahim, M.D., Ph.D., Mohs surgeon and associate professor in the department of dermatology at The University of Rochester Medical Center. "Progress has been made with clinicopathologic risk factor assessment. However, potential remains for these assessments to overestimate or underestimate risk. Gene expression profile testing assists us in assessing the biologic risk of individual tumors and providing personalized care for our patients, which may lead to risk appropriate reduction of treatment or increased treatment intensity and more appropriate referrals."

About DecisionDx-SCC

DecisionDx-SCC is a 40-gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous squamous cell carcinoma metastasis for patients with one or more risk factors. The test result, in which patients are stratified into a Class 1, 2A or 2B risk category, predicts individual metastatic risk to inform risk-appropriate management.

Peer-reviewed publications have demonstrated that DecisionDx-SCC is an independent predictor of metastatic risk and that integrating DecisionDx-SCC with current prognostic methods can add positive predictive value to clinician decisions regarding staging and management.

More information about the test and disease can be found at www.CastleTestInfo.com.

On May 20, 2021 Foundation Medicine, Inc. reported that the company and its collaborators will present a total of 29 studies, including two clinical science symposia presentations and two poster discussions, at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program (ASCO21) from June 4-8 (Press release, Foundation Medicine, MAY 20, 2021, View Source [SID1234580387]). Among the presentations are data reinforcing the role of comprehensive genomic profiling (CGP) in increasing equitable patient access to precision medicine tools, as well as studies highlighting the clinical utility of CGP and the power of real-world data to inform treatment decisions and better understand disparities in care.

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Highlights of these presentations include:

new data emphasizing how the lack of early CGP testing and clinical trial enrollment in patients of African ancestry may help explain disparities in prostate cancer;
clinical data reinforcing the value of tissue- and liquid-based CGP as tools for oncologists to identify predictive biomarkers and enable precision medicine; and
additional evidence of the power of real-world data from Foundation Medicine and Flatiron Health’s joint clinico-genomic database (CGDB) to inform treatment decisions.
"At our core, Foundation Medicine is focused on using the highest quality insights to transform cancer care for everyone, and the breadth of data we’re presenting at ASCO (Free ASCO Whitepaper) in collaboration with our research and industry partners reflects that commitment," said Brian Alexander, M.D., M.P.H., CEO at Foundation Medicine. "The data we’ll share with the oncology community will help us continue moving the needle on changing clinical care by showing the clinical value of CGP across the spectrum of cancers, as well as highlighting the need to consistently and equitably improve access to genomic testing so that every person facing a cancer diagnosis has the insights needed to inform the best possible care."

Understanding Genomic Ancestry and CGP Utilization in Men with Prostate Cancer

In a study conducted in collaboration with Sylvester Comprehensive Cancer Center at the University of Miami, researchers investigated the genomic landscape and therapeutic implications of CGP in prostate cancer across men of European and African ancestry. Researchers believe this is the largest known cohort of its kind that describes CGP utilization, the genomic landscape from CGP, and treatment patterns in prostate cancer across ancestry groups. The analysis revealed men of African ancestry were less likely to receive CGP earlier in their treatment course and less likely to be treated in clinical trials. The findings potentially advance the field’s understanding of ancestry-based disparities in prostate cancer.

[Ancestral characterization of the genomic landscape, comprehensive genomic profiling utilization, and treatment patterns may inform disparities in advanced prostate cancer: A large-scale analysis. Abstract #5003.]

Clinical Utility of Comprehensive Genomic Profiling

In a study exploring the genomic and immunologic profile of intrahepatic cholangiocarcinoma (IHCC) with IDH1/2 genetic alterations in partnership with The University of Texas MD Anderson Cancer Center and others, researchers found significant differences in alterations between IDH1+/IDH2+ IHCC and IDH wild-type IHCC. The data suggest these alterations are IHCC driver oncogenes and support investigation of IDH inhibitors in these patients.

[IDH1 and IDH2 driven intrahepatic cholangiocarcinoma (IHCC): A comprehensive genomic and immune profiling study. Abstract #4009]

In a real-world clinical outcomes study of alpelisib in patients with PIK3CA-mutated breast cancer conducted in partnership with UCSF Helen Diller Family Comprehensive Cancer Center, researchers validated the effectiveness of alpelisib in a diverse, real-world population. Results showed these patients had longer progression-free survival with alpelisib plus fulvestrant than with fulvestrant alone. The study also showed liquid biopsy CGP detected PIK3CA mutations at a similar rate to tissue biopsy, reinforcing the clinical utility of both testing types depending on the patient’s unique situation.

[Real world (rw) clinical outcomes on alpelisib (ALP) in patients (pts) with breast cancer (BC) and PIK3CA mutations (PIK3CAm). Abstract #1068]

As the cancer community works to expand access to precision medicine trials to more patients, the need for decentralized trials has become increasingly apparent. In the Alpha-T study, a clinical trial sponsored by Roche using Foundation Medicine’s precision enrollment services, researchers at multiple institutions, including UCSD Moores Cancer Center and Vanderbilt University Medical Center, are investigating patients with ALK-positive solid tumors, identified through either liquid or tissue biopsy, being treated with alectinib. Through remote support, patients are participating in the trial from their local care setting, demonstrating the potential of decentralized trials to increase broader and more diverse enrollment in clinical trials.

[Alpha-T: An innovative decentralized (home-based) phase 2 trial of alectinib in ALK-positive (ALK+) solid tumors in a histology-agnostic setting. Abstract #TPS3155]

Power of Real-World Data to Advance Personalized Medicine

Using the CGDB, researchers assessed outcomes for metastatic breast cancer patients with somatic BRCA or other homologous recombination (HR)-pathway mutations treated with a PARP inhibitor. Results suggested these patients had similar benefit from PARP inhibitor treatment compared to patients with germline BRCA mutations, supporting future studies of this targeted treatment approach for these patients.

[Analysis of real-world (RW) data for metastatic breast cancer (mBC) patients (pts) with somatic BRCA1/2 (sBRCA) or other homologous recombination (HR)-pathway gene mutations (muts) treated with PARP inhibitors (PARPi). Abstract #10512]

Leveraging routine CGP testing of metastatic castrate resistant prostate (mCRPC) cancer tissue samples, researchers discovered that patients with biomarkers routinely assessed by CGP, including AR amplification, may help predict which patients are likely to benefit from taxane chemotherapy instead of novel hormonal therapy.

[Using real-world outcomes to evaluate the predictive power of tissue-assessed genomic biomarkers for taxane versus novel hormonal therapy (NHT) outcomes in metastatic castration-resistant prostate cancer (mCRPC). Abstract #5054]

The following is a list of select abstracts that will be presented at the meeting. To access all abstracts being presented by Foundation Medicine and its collaborators, please visit: meetinglibrary.asco.org.

Abstract #

Title

Collaborator

Clinical Science Symposia

5003

Ancestral characterization of the genomic landscape, comprehensive genomic profiling utilization, and treatment patterns may inform disparities in advanced prostate cancer: A large-scale analysis.

University of Michigan Cancer Center, Sylvester Comprehensive Cancer Center, Harvard Medical School

4009

IDH1 and IDH2 Driven Intrahepatic Cholangiocarcinoma (IHCC): A comprehensive genomic and immune profiling study.

MD Anderson

Poster Discussions

10512

Analysis of real-world (RW) data for metastatic breast cancer (mBC) patients (pts) with somatic BRCA1/2 (sBRCA) or other homologous recombination (HR)-pathway gene mutations (muts) treated with PARP inhibitors (PARPi).

Beth Israel Deaconess Medical Center; Dana Farber Cancer Institute, Flatiron

3009

Prevalence of inferred clonal hematopoiesis (CH) detected on comprehensive genomic profiling (CGP) of solid tumor tissue or circulating tumor DNA (ctDNA).

Poster Presentations

5054

Using real-world outcomes to evaluate the predictive power of tissue-assessed genomic biomarkers for taxane versus novel hormonal therapy (NHT) outcomes in metastatic castration-resistant prostate cancer (mCRPC).

MD Anderson

5567

Assessment of predictive biomarker prevalence in molecularly defined adult-type ovarian granulosa cell tumors.

MD Anderson

TPS3143

TCF-001 TRACK (Target Rare Cancer Knowledge): A national patient-centric precision oncology trial for rare cancers.

University of California San Diego, TargetCancer Foundation​

TPS3155

Alpha-T: An innovative decentralized (home-based) phase 2 trial of alectinib in ALK-positive (ALK+) solid tumors in a histology-agnostic setting.

Roche,​ UCSD Moores Cancer Center, Vanderbilt University Medical Center

2599

Real-world pan-cancer landscape of frameshift mutations (FSM) and their role in predicting responses to immune checkpoint inhibitors (ICI) in patients (pts) with tumors with low tumor mutational burden (TMB).

​Huntsman Cancer Institute

1068

Real-world (rw) clinical outcomes on alpelisib (ALP) in patients (pts) with breast cancer (BC) and PIK3CA mutations (PIK3CAm).

University of California, San Francisco

2541

Genomic immunotherapy (IO) biomarkers detected on comprehensive genomic profiling (CGP) of tissue and circulating tumor DNA (ctDNA).

National Cancer Center Hospital East; Kashiwa, Japan

1036

Concordance of HER2+ status by IHC/ISH and ERBB2 status by NGS in a real-world clinicogenomic database and analysis of outcomes in patients (pts) with metastatic breast cancer (mBC).

Flatiron

539

Comprehensive genomic profiling (CGP) of 275 male breast cancer (BC) tissue (TBx) and liquid (LBx) biopsies: Comparative analysis to a female cohort (FBC) and therapeutic considerations.

Dana Farber Cancer Institute

9101

Identification of potential germline (GL) variants by routine clinical comprehensive genomic profiling (CGP) and confirmatory GL testing in 24 tumor types.

Dana Farber Cancer Institute

On May 20, 2021 NeoImmuneTech, Inc. (KOSDAQ: 950220), a clinical-stage T cell-focused biopharmaceutical company, reported that new data from two clinical trials evaluating the company’s lead asset NT-I7 (efineptakin alfa) will be presented during poster sessions at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, to be held in a virtual platform June 4-8, 2021 (Press release, NeoImmuneTech, MAY 20, 2021, View Source [SID1234580386]). The data come from clinical studies evaluating NT-I7, a novel long-acting human IL-7, 1. in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) as a treatment for advanced solid tumors, and 2. given concurrently with adjuvant chemotherapy in patients with high-grade gliomas.

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Details related to the poster presentations are as follows:

Title: Safety, Pharmacokinetics, Pharmacodynamics Profiles and Preliminary Antitumor Activity of Phase 1b/2a Study of NT-I7, a Long-Acting Interleukin-7, plus Pembrolizumab in Patients with Advanced Solid Tumors: The Phase 1b Data Report
Lead Author: Aung Naing, MD, The University of Texas MD Anderson Cancer Center
Abstract Number: 2594
Poster Session: Developmental Therapeutics—Immunotherapy, on demand starting at 9:00am ET, June 4, 2021

Title: A phase I/II study to evaluate the safety and efficacy of a novel long-acting interleukin-7, NT-I7, for patients with newly diagnosed high-grade gliomas after chemoradiotherapy: the interim result of the phase I data
Lead Author: Jian Li Campian, MD, PhD, Washington University School of Medicine in St. Louis/Siteman Cancer Center
Abstract Number: 2040
Poster Session: Central Nervous System Tumors, on demand starting at 9:00am ET, June 4, 2021

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., USA.

About NT-I7

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

On May 20, 2021 Xilio Therapeutics, a biotechnology company developing tumor-selective immuno-oncology therapies for patients with cancer, reported the presentation of data from preclinical studies of XTX202, its tumor-selective interleukin-2 (IL-2) product candidate, demonstrating selective anti-tumor activity and favorable tolerability with no systemic toxicity observed (Press release, Xilio Therapeutics, MAY 20, 2021, View Source [SID1234580385]). The data will be reported in a poster entitled "XTX202, a protein-engineered IL-2, exhibits tumor-selective activity in mice without peripheral toxicities in non-human primates" at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The poster will be made available on the ASCO (Free ASCO Whitepaper) Annual Meeting website at the start of the meeting on June 4, 2021 at 9am ET.

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Xilio is leveraging its proprietary platform to engineer novel molecules that are designed to be activated in the tumor microenvironment (TME) and have the potential to result in localized, tumor-selective clinical activity without dose-limiting toxicities. XTX202, Xilio’s lead cytokine product candidate, is an engineered form of IL-2 that is masked with a protein domain to prevent binding activity until cleaved off by TME-associated proteases.

"The power of IL-2 to activate the immune system as a cancer therapeutic is promising, but utility of IL-2 agents has historically been greatly reduced due to toxicities," said Rónán O’Hagan, Ph.D., chief scientific officer of Xilio. "We have engineered XTX202 to overcome those challenges, with key features designed to ensure it is released and activated locally within the TME, where it selectively binds to IL-2 receptors on immune cells. We are excited to present these data which, for the first time, demonstrate selective tumor-inhibition and favorable tolerability of XTX202 in preclinical models. With these data, we plan to complete IND-enabling studies and submit an IND application in the second half of 2021 to evaluate XTX202 in patients with solid tumors."

Data reported in the poster are from preclinical studies in both mouse and non-human primate (NHP) models, including comparisons between XTX202 and XTX200, a non-masked, parent version of XTX202, as well as aldesleukin, a synthetic form of IL-2 approved for certain cancer indications by the U.S. Food and Drug Administration. Key data include:

XTX202, in its masked form, did not bind to IL-2 receptors, and matrix metalloproteinase (MMP) activation of XTX202 restored full binding to IL-2 receptor beta that is found on immune activating CD8 T cells and natural killer cells, illustrating the tight, protease-dependent control of IL-2 activity conferred by XTX202.
XTX202 was engineered to eliminate binding to IL-2Ra in order to enhance immune activation by CD8 T cells and NK cells, and to minimize immune suppression by regulatory T cells. No binding to IL-2Ra was detectable even after MMP-dependent activation of XTX202.
XTX202 inhibited tumor growth in syngeneic mouse models as a single agent with no evidence of toxicity or peripheral immune activation, thus demonstrating tumor selective activity.
XTX202 matched the tumor growth inhibition activity of aldesleukin and the non-masked control XTX200, without activation of immune response outside the TME, thereby avoiding the body weight loss in mice that was associated with doses of XTX200 or aldesleukin required for tumor growth inhibition.
XTX202 was well-tolerated in repeat dose studies in NHPs at doses up to 30 mg/kg.
XTX202 is estimated to have a greater than 100-fold improvement in therapeutic index compared to aldesleukin.