On June 6, 2022 SOPHiA GENETICS (Nasdaq: SOPH), the creator of a global data pooling and knowledge sharing platform that advances data-driven medicine, reported an update on its multimodal DEEP-Lung-IV clinical study (NCT04994795) at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Sophia Genetics, JUN 6, 2022, View Source [SID1234615668]). This will be discussed during the company’s joint Innovation Symposium with GE Healthcare Monday, June 6th from 6:30 – 8:00 pm CDT.

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Immunotherapy has revolutionized the management of metastatic non-small cell lung cancer. Despite its promise, the majority of patients fail to respond to the therapy while being exposed to potentially severe side effects. Existing biomarkers are suboptimal as they do not allow to predict which patients will benefit from the therapy. There is an urgent need to identify biomarkers that are predictive of response to immunotherapy at the individual patient level.

New agreement signed with GE Healthcare to utilize Imaging Fabric to further accelerate radiomics analysis workflows

SOPHiA GENETICS launched the DEEP-Lung-IV clinical study to leverage its multimodal machine learning-powered analytics capabilities to identify multimodal predictive signatures of response to immunotherapy for patients with advanced lung cancer. Through its global footprint, the study is intended to maximize exposure of the machine learning algorithms to a wide range of diverse, real-world data. Insights from the DEEP-Lung-IV study will power one of the applications of the CarePath module of the SOPHiA DDMTM platform, offering advanced data visualization, cohorting, and predictive capabilities in a single solution.

To date, 19 sites across seven countries have signed up for participation in the study, including Roswell Park Comprehensive Cancer Center in New York. "I am personally very excited to join the DEEP-Lung-IV study. I see tremendous value in the multimodal machine learning-powered approach to real-world data analytics and look forward to potentially applying it to other clinical questions of high relevance in lung cancer", said Dr. Prantesh Jain, Assistant Professor of Oncology at Roswell Park Comprehensive Cancer Center. Together, these sites have already recruited over 500 patients.

Early findings are promising and conceptually validate the potential for multimodal signatures to predict response to immuno-chemotherapy at the individual patient level. First results will be discussed during SOPHiA GENETICS’ joint Innovation Symposium with GE Healthcare on Monday, June 6, at 6:30 pm CDT.

"We are very excited by the strong operational traction in recruiting patients to the study, as well as the promising early findings. With its unique machine learning-powered multimodal study design and its focus on collecting very diverse real-world data from lung cancer patients around the world, we feel that the DEEP-Lung-IV study has the potential to usher a new era of precision medicine that would enable predictions at the individual patient level. We look forward to further validating our vision of building a multimodal decentralized collective intelligence, leveraging on real-world data to generate novel insights at the individual patient level," said Dr. Philippe Menu, SVP & Chief Medical Officer, SOPHiA GENETICS.

SOPHiA GENETICS has also entered into an agreement with GE Healthcare to utilize their Imaging Fabric Core and Imaging Fabric Annotation Template, as part of the Edison Digital Health Platform. In the context of the DEEP-Lung-IV clinical study, Imaging Fabric services will be used to visualize, segment, and annotate lung lesions for medical imaging visualization and annotation purposes. This allows SOPHiA GENETICS to further accelerate proprietary radiomics analytics workflows in the context of the study, in particular to move towards automatic whole-body tumor identification, segmentation, and quantification.

"We’re eager to further strengthen our collaboration with SOPHiA GENETICS. The use of Imaging Fabric and the SOPHiA DDMTM Platform are key to create the world of tomorrow, in which we aim to jointly break data silos across data modalities to deliver insights to physicians to help them optimize patient treatment workflows. We look forward to seeing how the DEEP-Lung-IV study results can help improve outcomes for those diagnosed with lung cancer," said Ben Newton, MD, General Manager, GE Healthcare Oncology Solutions.

SOPHiA GENETICS’ DEEP-Lung-IV clinical study aims to predict immunotherapy treatment response upon first evaluation at the individual patient level using data across multiple modalities including genomics, radiomics, clinical, and biological data. The study also aims to validate an algorithm that will allow the prediction of outcomes of the individual patient such as progression-free survival (PFS) and overall survival (OS). This predictive model will help identify patients that are likely to benefit from immunotherapy versus those that are not. It will stratify patients according to risk, helping clinicians make more informed therapeutic decisions for their patients, supporting biopharma to ensure the right patients are selected for clinical trials.

On June 6, 2022 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, reported that the Company will present at the 2022 Jefferies Global Healthcare Conference in New York, New York on Friday, June 10, 2022 at 10:30 a.m. ET. Presenting on behalf of Fusion will be Chief Executive Officer John Valliant, Ph.D (Press release, Fusion Pharmaceuticals, JUN 6, 2022, View Source [SID1234615667]).

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A live webcast of the event will be available on the "Events and Presentations" page in the "Investors & Media" section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 60 days following the presentation.

On June 6, 2022 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported that Antengene has received approval by the Bellberry Human Research Ethics Committee (HREC) in Australia to initiate the Phase I Trial of ATG-018 in patients with advanced solid tumors and hematologic malignancies (ATRIUM Trial) (Press release, Antengene, JUN 6, 2022, View Source [SID1234615666]).

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ATG-018 is an orally-available, potent, selective small molecule ATR inhibitor. ATG-018 inhibits the ATR kinase, thus limiting cancer cells’ ability to repair damaged DNA, in a mechanism also known as synthetic lethality or the DDR.

The primary objective of the study is to evaluate the safety and tolerability of ATG-018 as a monotherapy, to determine the appropriate dose for Phase II studies and assess preliminary efficacy, if available; the secondary objective is to characterize the pharmacology of ATG-018. The study will be conducted in two parts (dose-escalation and dose-expansion). Icon Brisbane in Australia is the lead site for the study, which will be conducted at five sites across Australia.

"DNA is constantly exposed to damage by sources such as ultraviolet light, toxins, certain chemicals, and natural biochemical processes inside our cells. The DNA damage response (DDR) is able to identify DNA damage and to induce various biological processes that correct these changes." Said Dr Jim Coward, Chair of Icon’s Medical Oncology Research Committee and Associate Professor at University of Queensland School of Medicine. "The therapeutic landscape of antitumor agents targeting DDR pathways has rapidly expanded to include inhibitors of other key mediators of DNA repair and replication, such as ATR, ATM and DNA-PK[1]. Positive findings from the trials evaluating ATR inhibitors such as ATG-018 may help provide oncologists with a new tool for improving patient outcomes in challenging cases and give them new hope when other therapies have failed."

Dr. Bo Shan, Antengene’s Chief Scientific Officer commented, "ATG-018 has a solid preclinical data package including efficacy as a monotherapy in solid tumor models, oral bio-availability and potential predictive biomarkers for response. It is also one of Antengene’s first in-house programs to reach the clinic. The differentiated profile of ATG-018 may enable it to be used as monotherapy and open the door for novel collaborations and combination regimens that could benefit cancer patients around the world. We are very pleased to receive HREC approval for the Phase I ATRIUM trial for ATG-018 and we look forward to collaborating with Dr. Coward and the team at Icon Brisbane on this exciting trial."

About the ATRIUM Trial

The ATRIUM trial is a Phase I multi-center, open-label, dose finding study of ATG-018 monotherapy in patients with advanced solid tumors or hematologic malignancies. The primary objective of the study is to evaluate the safety and tolerability of ATG-018 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and/or biologically effective dose of ATG-018 monotherapy and preliminary efficacy, if available. The secondary objective is to characterize the pharmacology of ATG-018. As a Phase I study, there will be intensive safety monitoring throughout the trial.

About ATG-018

Discovered by the internal R&D Team at Antengene, ATG-018 is an oral, potent, selective small molecule inhibitor targeting ataxia telangiectasia and Rad3-associated (ATR) kinase. ATR kinase belongs to the phosphoinositide 3 kinase-related family. Inhibiting ATR kinase leads to increased accumulation of single-strand DNA breaks, particularly meaningful for tumor cells which rely on DNA damage repair (DDR). Preclinical studies have demonstrated that ATR inhibitor monotherapy or combination with other drugs (including DDR agents) could be promising therapeutic strategies for solid tumors (including gastric, esophageal, squamous cell carcinoma) and hematologic malignancies (chronic lymphocytic leukemia [CLL], diffuse large B-cell lymphoma [DLBCL] and multiple myeloma [MM]).

According to a preclinical poster presented at 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2022) Annual Meeting, ATG-018 has demonstrated potent in vitro and in vivo monotherapy efficacy in solid tumor/hematologic cancer models with certain homologous recombination deficiencies. These data were supported by a series of genetic alterations that correlated with ATG-018 sensitivity and could be potential predictive biomarkers. Taken together, these data suggest that ATG-018 could be a promising therapeutic agent for patients with such homologous recombination deficiencies/genetic alterations.

On June 6, 2022 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that it has released the latest results from a Phase Ib/II study of the third-generation tyrosine kinase inhibitor (TKI) olverembatinib (HQP1351) in patients with metastatic gastrointestinal stromal tumor (GIST) who were resistant to or failed prior TKI treatment, in a Poster Discussion session at the 58th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Ascentage Pharma, JUN 6, 2022, View Source;the-first-dataset-of-olverembatinib-hqp1351-in-patients-with-gist-demonstrates-therapeutic-potential-with-a-clinical-benefit-rate-of-83-3-301562391.html [SID1234615665]).

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Entering the fifth consecutive year in which its abstracts were selected for presentations by the ASCO (Free ASCO Whitepaper) Annual Meeting, Ascentage Pharma showcased results from multiple clinical trials of its five drug candidates, including the first dataset of olverembatinib in patients with GIST demonstrating a clinical benefit rate (CBR) of 83.3% in the subgroup with TKI-resistant succinate dehydrogenase- (SDH-) deficient GIST.

Although the introduction of TKIs has transformed the management of GIST, TKI-resistant, locally advanced/metastatic GIST remains a major clinical challenge, particularly for patients with SDH-deficient GIST, which is not sensitive to existing TKIs and lacks standard-of-care treatment options.

Olverembatinib is a novel drug developed by Ascentage Pharma and recently received approval in China for the treatment of adult patients with TKI-resistant chronic phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation, making olverembatinib the first and only approved third-generation BCR-ABL inhibitor in China. While being clinically developed and applied for the treatment of hematologic malignancies, olverembatinib is also being investigated in preclinical and clinical studies for the treatment of GIST, and has already demonstrated promising antitumor activity in multiple preclinical models of GIST.

Prof. Baibo Qiu of Sun Yat-sen University Cancer Center who is the principal investigator of this study, said, "Olverembatinib is a novel third-generation TKI with potent inhibitory activity against a range of kinases, including ABL, KIT, PDGFR, FGFR, b-RAF, DDR1, and FLT3, and has shown antitumor activity in multiple preclinical models of GIST. In this Phase Ib/II clinical study being conducted in China, olverembatinib has demonstrated preliminary efficacy in patients with TKI-resistant GIST, especially in the SDH-deficient subgroup. These data signal olverembatinib’s potential as a treatment option for patients with SDH-deficient GIST who currently lack standard of care treatment and suggest it could bring a major breakthrough to this therapeutic area."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, "In the past few years, olverembatinib has amassed a wealth of data demonstrating its therapeutic utility in a number of hematologic malignancies such as CML. These clinical data presented at this year’s ASCO (Free ASCO Whitepaper) meeting show that olverembatinib also has clinical potential for the treatment of GIST, thus suggesting a wide therapeutic window for the drug candidate as a multi-kinase inhibitor. Furthermore, we are proud to be able to present clinical development progress for a number of Ascentage Pharma’s drug candidates, which highlight our capabilities in global innovation. Honoring our mission of addressing unmet clinical needs in China and around the world, we are now accelerating our clinical programs to bring more safe and effective therapeutics to patients in need."

The highlights of this abstract on olverembatinib are as follows:

Promising antitumor activity of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor- (TKI-) resistant succinate dehydrogenase- (SDH-) deficient gastrointestinal stromal tumor (GIST).

Abstract: #11513

This is an open-label, multicenter Phase Ib/II study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and antitumor activity of olverembatinib in Chinese patients with locally advanced or metastatic GIST whose disease was resistant or failed to respond to imatinib or other TKIs.

As of January 30, 2022, 39 patients had been enrolled. Olverembatinib was administered orally once every other day (QOD) in 28-day repeated cycles. After 3 patients were treated with 20 mg, other patients were randomly allocated in a 1:1:1 ratio to 30, 40, and 50 mg regimens.

Efficacy Results:
In the 8 patients with KIT wild-type GIST, 6 were confirmed as SDH-deficient: 2 had partial responses (PRs), 1 patient’s tumor shrunk by 35.9% and lasted for 16 cycles, and another patient’s tumor shrunk by 54.2% at the first evaluation. 4 patients had stable disease (SD) as the best response for 2, 6, 14, and 36 cycles, resulting in a CBR of 83.3% (complete response [CR]+PR+SD ≥ 4 cycles).
Among 31 patients who had KIT or PDGFRA mutations, 13 had stable disease for at least 2 cycles as the best response, 8 withdrew early, and 10 had progressive disease before Cycle 3.

A total of 36 (92.3%) patients experienced treatment-emergent adverse events, most of which were mild or moderate. Common treatment-related adverse events (≥ 20%) included increased leukocyte (59.0%) and neutrophil (46.2%) counts, anemia (20.5%), constipation or asthenia (35.9% each), hyperuricemia (25.6%), hypoalbuminemia (23.1%), and elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) (20.5% each).

Conclusions: olverembatinib was well tolerated and showed antitumor activity in patients with TKI-resistant SDH-deficient GIST. These promising findings warrant further investigation.
Appendix: A list of Ascentage Pharma’s abstracts selected by this year’s ASCO (Free ASCO Whitepaper) Annual Meeting

Drug Candidate

Abstract Title

Abstract #

Format

olverembatinib（HQP1351）

Promising antitumor activity of olverembatinib (HQP1351) in patients (pts) with tyrosine kinase inhibitor- (TKI-) resistant succinate dehydrogenase- (SDH-) deficient gastrointestinal stromal tumor (GIST).

#11513

Poster discussion

Lisaftoclax (APG-2575)

A phase Ib/II study of lisaftoclax (APG-2575), a novel BCL-2 inhibitor (BCL-2i), in patients (pts) with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL).

#7543

Poster presentation

Phase Ib/II study of BCL-2 inhibitor lisaftoclax (APG-2575) safety and tolerability when administered alone or combined with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor in patients with estrogen receptor-positive (ER⁺) breast cancer or advanced solid tumors.

#TPS1122

Poster presentation

Alrizomadlin (APG-115)

Newly updated activity results of alrizomadlin (APG-115), a novel MDM2/p53 inhibitor, plus pembrolizumab: Phase 2 study in adults and children with various solid tumors.

#9517

Poster discussion

APG-2449

First-in-human phase I results of APG-2449, a novel FAK and third-generation ALK/ ROS1 tyrosine kinase inhibitor (TKI), in patients (pts) with second-generation TKI-resistant ALK/ROS1 non-small-cell lung cancer (NSCLC) or mesothelioma.

#9071

Poster presentation

Pelcitoclax (APG-1252)

Updated study results of pelcitoclax (APG-1252) in combination with osimertinib in patients (pts) with EGFR-mutant non-small-cell lung cancer (NSCLC).

#9116

Poster presentation

First-in-human study of pelcitoclax (APG-1252) in combination with paclitaxel in patients (pts) with relapsed/refractory small-cell lung cancer (R/R SCLC).

e20612

Publication-Only

About Olverembatinib (HQP1351)

Developed by Ascentage Pharma with support from the National Major New Drug Discovery and Manufacturing program, the orally active, third-generation BCR-ABL inhibitor olverembatinib is the first China-approved third-generation BCR-ABL inhibitor targeting drug-resistant chronic myeloid leukemia (CML). Olverembatinib can effectively target a spectrum of BCR-ABL mutants, including the T315I mutation. Meanwhile, olverembatinib is being investigated for the treatment of gastrointestinal stromal tumor (GIST) in China.

The clinical results of olverembatinib in hematologic malignancies have been selected for oral presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meetings for four consecutive years since 2018, and was nominated for "Best of ASH (Free ASH Whitepaper)" in 2019. Olverembatinib has already entered a Phase Ib study in the US and has been granted 3 Orphan Drug Designations (ODDs) and 1 Fast Track Designation (FTD) from the FDA, and 1 Orphan Designation by the EU.

In July 2021, Ascentage Pharma and Innovent Biologics (1801.HK) reached the agreement regarding the joint development and commercialization of olverembatinib in the oncology field in China.

On June 6, 2022 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that it has released the updated results from a Phase II study of the MDM2-p53 inhibitor alrizomadlin (APG-115) plus pembrolizumab in adults and children with various solid tumors in a Poster Discussion session at the 58th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Ascentage Pharma, JUN 6, 2022, View Source;ascentage-pharma-releases-updated-results-demonstrating-the-therapeutic-potential-of-alrizomadlin-apg-115-plus-pembrolizumab-in-patients-with-solid-tumors-who-progressed-on-immunotherapies-301562392.html [SID1234615664]).

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Entering the fifth consecutive year in which its abstracts were selected for presentations by the ASCO (Free ASCO Whitepaper) Annual Meeting, Ascentage Pharma showcased results from multiple clinical trials of its five drug candidates, including the much-anticipated data of alrizomadlin plus pembrolizumab, updated from the data at last year’s oral presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting. The updated results further validate the combination therapy’s efficacy in patients with immuno-oncologic- (I-O) drug-resistant or recurrent melanoma, including two complete responses (CRs), an objective response rate (ORR) of 11% and a disease control rate (DCR) of 57%. The abstract also reports favorable clinical benefit in patients with malignant peripheral nerve sheath tumour (MPNST), demonstrated by a DCR of 50%. MPNST is a rare pediatric type of sarcoma lacking effective treatment options.

"Ascentage’s novel oral MDM2 inhibitor (alrizomadlin APG-115) continues to be well tolerated in combination with pembrolizumab and provides clinical benefit in several I-O relapse refractory tumor types, specifically various melanoma subtypes as well as MPNST, a rare pediatric sarcoma tumor with no available approved therapies", said Dr Bartosz Chmielowski, MD, Associate Professor from the Melanoma and Sarcoma program at UCLA, who presented the updated results at ASCO (Free ASCO Whitepaper) 2022.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, "Alrizomadlin, a China-developed novel drug with first-in-class potential, is the first MDM2-p53 inhibitor entering clinical studies in China. These data we presented at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting validates alrizomadlin’s therapeutic potential in patients with solid tumors that progressed on I-O drugs, thus signaling a potential new treatment option for patients with solid tumors. Furthermore, we are proud to be able to present clinical development progress for a number of Ascentage Pharma’s drug candidates, which highlight our capabilities in global innovation. Honoring our mission of addressing unmet clinical needs in China and around the world, we are now accelerating our clinical programs to bring more safe and effective therapeutics to patients in need."

The highlights of this abstract on alrizomadlin are as follows:

Newly updated activity results of alrizomadlin (APG-115), a novel MDM2/p53 inhibitor, plus pembrolizumab: Phase 2 study in adults and children with various solid tumors.

Abstract: #9517

This US/Australian multicenter trial evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of alrizomadlin in combination with pembrolizumab in patients with advanced solid tumors.

As of March 1, 2022, 150 patients had been enrolled in the Phase II study. Alrizomadlin was orally administered QOD at the recommended Phase II dose (RP2D) of 150 mg in combination with intravenously administered pembrolizumab. This study consists of 6 cohorts: PD-1/PD-L1-refractory melanoma (n=60), non-small cell lung cancer (NSCLC, n=19)/STK-11-mutant lung adenocarcinoma (n=7), ATM-mutant solid tumors (n=20); liposarcoma (n=17), urothelial cancer (n=13), and MPNST failed prior standard-of-care therapies (n=14).

Efficacy Results:
In the 46 efficacy evaluable (EE) patients with melanoma progressed on PD-1/PD-L1 inhibitors, the confirmed ORR was 10.9% (2CRs+3 partial responses [PRs]/46EEs). In the cutaneous and uveal melanoma sub-cohorts, confirmed ORRs were 20% (2CRs+2PRs/20EEs) and 6.7% (1PR/15EEs), and DCRs (including confirmed PR, CR, and stable disease ≥ 4 cycles) were 55% (2PRs+2CRs+7SDs/20EEs) and 73.3% (1PR+10SDs/15EEs), respectively.
In the MPNST cohort, the DCR was 50% (6SDs/12EEs).
The PD-1/PD-L1-refractory NSCLC, urothelial, and liposarcoma cohorts each reported 1 confirmed PR.

Common treatment-related adverse events (TRAEs; ≥ 10%) of any grade were nausea, thrombocytopenia, vomiting, fatigue, decreased appetite, diarrhea, neutropenia, and anemia.

Conclusions:
This Phase II study showed that alrizomadlin in combination with pembrolizumab was well tolerated.
Preliminary and interim results of the combination therapy demonstrated clinical benefit for patients with relapsed/refractory melanoma and high DCRs in the cutaneous and uveal melanoma sub-cohorts.
Alrizomadlin combined with pembrolizumab demonstrates clinical benefit in patients with MPNST,with a 50% DCR, an orphan pediatric indication with no effective standard of care.