On May 30, 2024 Akeso, Inc. (HKEX: 9926.HK) ("Akeso," "we," or the "Company") reported that the Phase III clinical trial, HARMONi-2 or AK112-303, met its primary endpoint of progression-free survival (PFS) (Press release, Akeso Biopharma, MAY 30, 2024, View Source [SID1234643890]). HARMONi-2 evaluated monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors have positive PD-L1 expression (PD-L1 TPS >1%). HARMONi-2 is a single region, multi-center, double-blinded Phase III study sponsored by Akeso with data generated and analyzed by Akeso.

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At a prespecified interim analysis conducted by an independent Data Monitoring Committee, ivonescimab demonstrated a statistically significant and clinically meaningful improvement in PFS by blinded independent radiology review committee (BICR) compared to pembrolizumab. The PFS benefit was demonstrated across clinical subgroups, including those with PD-L1 low expression (PD-L1 TPS 1-49%), PD-L1 high expression (PD-L1 TPS >50%), squamous and non-squamous histologies, as well as other high-risk patients.

There are no known Phase III clinical trials in NSCLC which have shown a statistically significant improvement compared to pembrolizumab in a head-to-head setting.

The Phase III HARMONi-2 study, along with the approval of ivonescimab in China in combination with chemotherapy based on the results of the HARMONi-A trial, provides clear evidence supporting the purposefully-engineered, differentiated mechanism of action of ivonescimab, a PD-1 / VEGF bispecific antibody evidencing cooperative binding characteristics, and its opportunity to improve upon the existing standards of care for solid tumors.

"HARMONi-2 clearly demonstrates that ivonescimab has strong clinical values globally as well as commercial potentials." stated Dr. Michelle Xia , Chairwoman, President and Chief Executive Officer of Akeso. "ivonescimab is the next generation in PD-1 directed immunotherapy, and its potential to make a significant difference in the lives of patients with lung cancer and prospectively other tumors."

Conference Call

Akeso, Inc. (HKEX: 9926.HK) ("Akeso," "we," or the "Company") will host a conference call to discuss recent updates related to ivonescimab on Friday May 31, 2024, before the market opens.

About Ivonescimab

Ivonescimab, known as AK112 is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with higher affinity when in the presence of both PD-1 and VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the tumor microenvironment with over 18-fold increased binding affinity to PD-1 in the presence of VEGF in vitro, and over 4-times increased binding affinity to VEGF in the presence of PD-1 in vitro.[1] This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days,[1] is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was discovered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 1,600 patients have been treated with ivonescimab in clinical studies globally. Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two Phase III clinical trials, HARMONi and HARMONi-3.

The safety profile of ivonescimab is manageable and consistent with known risks for PD-1 and VEGF inhibiting drugs. In the first Phase III study to be presented at ASCO (Free ASCO Whitepaper), "Ivonescimab combined with chemotherapy in patients with EGFR-mutant non-squamous NSCLC who progressed on EGFR TKI treatment (AK112-301): A randomized, double-blind, multi-center, phase 3 trial," 5.6% of patient discontinues ivonescimab due to adverse events.

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to a placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a third-generation EGFR TKI (e.g., osimertinib).

HARMONi-3 is a Phase III clinical trial which is designed to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic squamous NSCLC.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was approved for marketing authorization in China in May 2024.

About Lung Cancer

Lung cancer is believed to impact approximately 600,000 people across the United States, United Kingdom, Spain, France, Italy, Germany, and Japan.[2] NSCLC is the most prevalent type of lung cancer and represents approximately 80% to 85% of all incidences.[3] Among patients with non-squamous NSCLC, approximately 15% have EGFR-sensitizing mutations in the United States and Europe.[4] Patients with squamous histology represent approximately 25% to 30% of NSCLC patients.

On May 30, 2024 InxMed Co., Ltd, a clinical-stage biotechnology company developing innovative therapies against tumor-treatment resistance and metastasis, reported results from the Phase Ib/II clinical trial of ifebemtinib, the company’s focal adhesion kinase (FAK) inhibitor, in combination with garsorasib, a specific inhibitor of the KRAS G12C mutation, for the first-line treatment of non-small cell lung cancer (NSCLC) with KRAS G12C mutation (Press release, InxMed, MAY 30, 2024, View Source [SID1234643889]).

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These results will be featured in a poster presentation (Abstract: 8605 | Poster #469) at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 31-June 4, 2024, in Chicago, IL.

As of the cutoff date of May 10, 2024, a total of 33 subjects were enrolled in the study. Among the 31 evaluable patients, the antitumor responses were assessed and summarized as follows:

The objective response rate (ORR) was 90.3% (95% CI: 74.3, 98.0), and the disease control rate (DCR) was 96.8% (95% CI: 83.3, 99.9). A total of 28 partial responses (PRs) and two stable diseases (SDs) were reported. Twenty-six out of 28 PRs were confirmed thus far.
The data for median duration of response (DOR), progression-free survival (PFS), and overall survival (OS) are still maturing.
The overall safety profile of the combination of ifebemtinib with garsorasib is consistent with either ifebemtinib or garsorasib monotherapy. Most treatment-related adverse events (AEs) were Grade 1 or 2, and some Grade 3 AEs were reported.
"The objective responses in patients exceeded our initial expectations. The combination regimen was well tolerated with known, non-overlapping, and manageable AEs from both agents," said Zhengbo Song, M.D., Associate Professor, Director of Phase 1 Unit, Zhejiang Cancer Hospital, University Chinese Academy of Sciences and Principal Study Investigator. "These data warrant further investigation to assess the potential of ifebemtinib to impact the future standard of care for KRAS G12C mutant-driven NSCLC, with or without immunotherapies in the combination regimen."

"We are highly encouraged by the results of the current clinical study of ifebemtinib in NSCLC. RAS mutations account for approximately 30 percent of all cancer patients, and KRAS mutations, including the G12C mutation, wreak havoc in many people with solid tumors, including lung, pancreatic, and colorectal cancers," stated James McLeod, M.D., Chief Medical Officer of InxMed. "With recent rapid advances in KRAS G12C inhibitors comes the need for further improving clinical responses and safety/tolerability profiles of treatment regimens. We have studied FAK tumor biology and designed the combination therapy with KRAS inhibitors based on our deep understanding of FAK’s roles in the tumor defense mechanism. We are pleased to see that ifebemtinib significantly amplifies the clinical responses of the combination regimen."

Dr. McLeod added, "The current data set, albeit early with PFS and DOR data, is still maturing but is consistent with the results from our clinical trials in other tumor types. These initial findings demonstrate the potential of ifebemtinib to become an anchor component in combination regimens with chemotherapies, targeted therapies, or immunotherapies. We will continue further exploring the clinical utility of ifebemtinib in combination therapy and certainly welcome collaborations with global leaders in cancer therapies."

About Ifebemtinib
Ifebemtinib (IN10018, BI853520) is a highly selective, orally administered, small molecule inhibitor for focal adhesion kinase, which has significant synergies with a broad spectrum of therapeutic modalities. Clinically, ifebemtinib has demonstrated therapeutic synergies with chemotherapy agents, targeted therapies, and immunotherapies. InxMed is currently pursuing a registrational trial in platinum-resistant ovarian cancer in China, and multiple proof-of-concept trials are ongoing in lung, colorectal, melanoma, and pancreatic cancers, with select tumor types to progress into pivotal clinical trials. Thus far, more than 600 patients have been treated with ifebemtinib, and a favorable safety and tolerability profile was observed.

Ifebemtinib was granted Breakthrough Therapy Designation from the China National Medical Products Administration (NMPA) and Fast-Track designation from the U.S. Food and Drug Administration (FDA). InxMed plans to submit a New Drug Application to the NMPA in early 2025.

On May 30, 2024 Prelude Corporation (PreludeDx), a leader in precision diagnostics for early-stage breast cancer, reported that it will share data demonstrating the power of its DCISionRT test to better predict radiation therapy (RT) benefit in comparison to clinicopathologic risk factors for women with ductal carcinoma in situ (DCIS) at The American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), to be held on May 31 – June 4, 2024 at the McCormick Place in Chicago (Press release, PreludeDx, MAY 30, 2024, View Source [SID1234643888]).

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Of particular importance, the DCISionRT biosignature identified a low-risk group of patients with no significant benefit from ET or RT after breast-conserving surgery.

"We look forward to sharing the latest data at ASCO (Free ASCO Whitepaper) that reaffirms DCISionRT’s prognostic and predictive value of the test to reclassify recurrence risk based on clinicopathology alone, and that the test’s impact is not altered by use of endocrine therapy," said Dan Forche, President and CEO of PreludeDx.

PreludeDx American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Poster to Be Presented

Title: Identification of DCIS patients with low-risk clinicopathology who benefit from radiation therapy with and without endocrine therapy after breast-conserving surgery assessed with the 7-gene biosignature
Presenter: Pat W. Whitworth, MD, Nashville Breast Center, Nashville, TN
Date: Sunday, June 2, 9:00 a.m. CT

About DCISionRT for Breast DCIS

DCISionRT is the only risk assessment test for patients with ductal carcinoma in situ (DCIS) that predicts radiation therapy benefit. Patients with DCIS have cancerous cells lining the milk ducts of the breast, but they have not spread into surrounding breast tissue. In the US, over 60,000 women are newly diagnosed with DCIS each year. DCISionRT, developed by PreludeDx on technology licensed from the University of California San Francisco, and built on research that began with funding from the National Cancer Institute, enables physicians to better understand the biology of DCIS. DCISionRT combines the latest innovations in molecular biology with risk-based assessment scores to assess a woman’s individual tumor biology along with other pathologic risk factors and provide a personalized recurrence risk. The test provides a Decision Score that identifies a woman’s risk as low or elevated. Unlike other risk assessment tools, the DCISionRT test combines protein expression from seven biomarkers and four clinicopathologic factors, using a non-linear algorithm to account for multiple interactions between individual factors in order to better interpret complex biological information. DCISionRT’s intelligent reporting provides a woman’s recurrence risk after breast conserving surgery alone and with the addition of radiation therapy. In turn, this new information may help patients and their physicians to make more informed treatment decisions.

On May 30, 2024 Servier, a leader in oncology committed to delivering transformative therapies to patients, reported that it will underwrite a panel hosted by The Atlantic titled: "Bridging the Gap in Cancer Care for Adolescents and Young Adults" (AYA) (Press release, Servier, MAY 30, 2024, View Source [SID1234643886]). The event, which will also include an art exhibit showcasing the challenges and triumphs of the AYA cancer patient population, will take place in Chicago, concurrently with the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"At Servier, our mission is to support patients far beyond delivering transformative new medicines," said David K. Lee, CEO of Servier Pharmaceuticals. "As a private Foundation, we are uniquely positioned to commit to prioritizing the long-term welfare of the patients we serve. Part of our commitment to patient-centric innovation involves fostering critical conversations about the experiences and needs of patients who are navigating life during and after a cancer diagnosis. We believe that continued dialogue on this important topic will drive advancements in care and improve outcomes for AYA patients in the future."

According to the National Cancer Institute, an estimated 84,100 AYAs between the ages of 15 to 39 will be diagnosed with cancer in the United States in 2024. This accounts for about 4.2% of all cancer diagnoses.1

These people also experience challenges distinct from those of pediatric and adult patients, and despite increased focus on survival and quality of life for AYA cancer patients, gaps in knowledge remain.

"Being governed by a private Foundation allows us to prioritize the needs of patients and take a long-term approach to our global impact on healthcare," said Arnaud Lallouette, Executive Vice President, Global Medical and Patient Affairs at Servier. "At Servier, we are inspired by the resilience of our patients and are honored to work hand in hand with them to not just address medical needs, but to build a more equitable healthcare system that addresses their comprehensive needs."

This dedication is evident in our patient-first philosophy, which guides every aspect of our operations. From pioneering research and development to meaningful community engagement, Servier is steadfast in its mission to improve the lives of cancer patients worldwide.

The event will be held on Friday, May 31 at 6:30 PM CT at the Lacuna Lofts in Chicago, IL. For more information and to register, visit: View Source

*PatientView’s 2023-2024 Corporate Reputation of Pharma

1 "Adolescents and Young Adults (Ayas) with Cancer." National Institute of Health, April 26, 2024. View Source

On May 20, 2024 Adela, Inc., an innovator in blood testing for molecular residual disease (MRD) monitoring and early cancer detection through a proprietary genome-wide methylome enrichment technology, reported that it will present results demonstrating the ability of its tissue-agnostic MRD assay to predict recurrence in head & neck cancer, during an Oral Presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 3, 2024 (Press release, Adela, MAY 30, 2024, View Source;neck-cancer-at-the-american-society-of-clinical-oncology-2024-meeting-302158653.html [SID1234643884]).

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"MRD tests have the potential to enable clinicians to individualize patient treatment based on a patient’s likelihood of a future recurrence. In addition, these tests can assist with identifying patients who may benefit from being more closely monitored with imaging to detect and treat a recurrence as early as possible," said Geoffrey Liu, MSc, MD, Senior Scientist, University Health Network – Princess Margaret Cancer Centre. "We are highly encouraged by these results demonstrating the ability of this genome-wide methylome enrichment platform to identify recurrences in head & neck cancer in advance of clinical presentation or routine imaging."

The ability of Adela’s assay to quantify cfDNA cancer signal and predict recurrence was evaluated in individuals diagnosed with stage I-IVB human papillomavirus (HPV)-negative and HPV-positive head and neck cancer treated at University Health Network – Princess Margaret Cancer Centre. This training analysis included 432 plasma samples collected from 130 patients (a subset of the full cohort of >1,100 plasma samples from >300 individuals). Blood draws occurred before and after curative intent treatment, and in a subset of patients, at 12 and 24 months post-curative intent treatment. Adela’s MRD assay demonstrated the ability to identify patients more likely to recur than not, based on the landmark blood draw (mean 3 months following curative intent treatment), and also at the surveillance timepoints.

Significant differences in recurrence-free survival (RFS) were observed, with a hazard ratio (HR) of 6.31 (P<0.001) at the landmark timepoint, and an HR of 12.95 (P<0.001) for surveillance timepoints, when patients were stratified by MRD positivity. MRD status correlated with RFS in both HPV-positive and HPV-negative disease. Lead time between MRD positivity and recurrence was up to 19.3 months, with a mean lead time of 5.1 months.

"Up to 80% of recurrences in patients with head & neck cancer are not detected until symptoms or physical findings are reported by the patient1. Routine surveillance for recurrences with MRD testing can enable earlier detection and treatment of recurrences with immunotherapy," said Dr. Anne-Renee Hartman, Chief Medical Officer of Adela. "We are excited about the potential of our tissue-agnostic approach to MRD detection for both HPV-positive and HPV-negative head & neck cancer to address this strong unmet need."

Validation results from a held-out test set from the cohort will be presented at a future meeting. A Research Use Only (RUO) version of Adela’s MRD test is currently available to biopharmaceutical companies and other investigators for use in biomarker discovery and drug development. Adela plans to commercialize the test for clinical use in 2025.

Presentation Details

Abstract # 3009: Performance characteristics of a tissue-agnostic genome-wide methylome enrichment MRD assay for head and neck malignancies.
Geoffrey Liu2
Mon June 3, 2024 4:42 PM CDT
Hall D2