On October 17, 2023 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported the publication of the abstract for a proffered paper session at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 (ESMO 2023) relating to selected clinical data from the company’s ongoing Phase 2 clinical trial evaluating darovasertib in combination with crizotinib in patients having metastatic uveal melanoma (MUM) (Press release, Ideaya Biosciences, OCT 17, 2023, View Source [SID1234636087]).

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Dr. Meredith McKean, M.D., MPH, Director, Melanoma and Skin Cancer Research at Sarah Cannon Research Institute, who is a clinical investigator on the Phase 2 clinical trial, will present the clinical data as summarized in the abstract, as follows:

Session No. 1081O
Title: ctDNA reduction and clinical efficacy of the darovasertib + crizotinib (Daro + Crizo) combination in metastatic uveal melanoma (MUM)
Date: Monday, October 23, 2023 at 8:50-9:00 am CEST
Dr. Meredith McKean, M.D., MPH, Sarah Cannon Research Institute (Nashville, TN, U.S.A)
In summary, the Phase 2 evaluation of the darovasertib and crizotinib combination in first-line and pretreated MUM patients showed a manageable safety profile and demonstrated clinical efficacy that appears superior to current standards of care. Human leukocyte antigen (HLA)-A*02:01 (HLA-A2) status was determined in a subset of patients enrolled in the company’s clinical trials evaluating darovasertib. Clinical efficacy was observed in both HLA-A2 positive (HLA-A2(+)) and HLA-A2 negative (HLA-A2(-)) patients. ctDNA was reduced in almost all patients and ctDNA molecular responses were deep and sustained in the majority of patients.

The reported data support IDEAYA’s ongoing registrational Phase 2/3 study for potential accelerated approval of darovasertib and crizotinib for treatment of first-line HLA-A2(-) MUM patients, where there are no FDA approved therapies.

A press release summarizing the top-line results will be available on Monday, October 23, 2023, at approximately 6:00 am ET, and will be available on the Company’s website, at its Investor Relations portal (View Source).

On October 17, 2023 ConcertAI’s TeraRecon, the advanced visualization and clinical AI SaaS company, reported its strategic collaboration with Optellum Ltd (Oxford, UK), a global leader in AI clinical decision support for early lung cancer diagnosis and precision treatment planning (Press release, ConcertAI, OCT 17, 2023, View Source [SID1234636086]). Through this partnership, the Optellum Virtual Nodule Clinic solution will be seamlessly integrated into TeraRecon’s Eureka Clinical AI platform, with the goal of helping clinicians across their install base drive more early lung cancer diagnoses and curative treatments. Eureka is the first such enterprise AI platform to integrate with Optellum.

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Lung cancer often shows no symptoms until a late stage when treatment options are more limited and outcomes less positive. However, continuous and automated analysis of the approximately 90 million CT scans US patients receive per year, such as emergency room and cardiac studies, could enable an "early detection system." Virtual Nodule Clinic, the first FDA and CE-MDR-cleared decision support for early-stage lung cancer, integrates a Patient Discovery AI, based on Natural Language Processing, with a clinically validated Lung Cancer Prediction (LCP) score based on imaging AI/Radiomics and deep-learning neural networks. The combination assists clinicians in detecting at-risk patients across a health system and prioritization of those at highest risk for follow-up interventions.

The integration of Virtual Nodule Clinic with the Eureka Clinical AI platform supports thoracic oncology care teams, led by pulmonologists, to identify and track more patients, earlier, with accelerated time to a confirmatory cancer diagnosis while reducing invasive procedures on benign lesions. TeraRecon’s solutions are deployed 1000’s of locations, and now combined with with Optellum’s AI solutions, medical professionals around the world will be able to provide timely, personalized lung cancer care.

"ConcertAI is one of the leading cancer research and clinical AI-focused companies in the world. TeraRecon’s collaboration with Optellum marks a significant milestone in advancing lung cancer diagnosis and aiding thoracic oncology teams in treatment," said Jeff Elton, PhD, CEO of ConcertAI. "The addition of the Virtual Nodule Clinic solution to the TeraRecon Eureka Clinical AI platform will provide thorasic care teams and pulmonologists with state-of-the-art tools to identify and diagnose early-stage lung cancer efficiently and accurately."

"We are thrilled to partner with ConcertAI’s TeraRecon to expand the reach of Optellum’s Virtual Nodule Clinic to drive patient identification and stage-shift across their customer base," said Václav Potěšil, PhD, Founder & Chief Business Officer at Optellum. "Our ultimate goal is to radically reshape lung cancer outcomes, leveraging the power of the Optellum AI platform to drive the right patients into early intervention and precision treatment with targeted- and immune-therapies, and save thousands of lives."

The companies will announce their partnership at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) congress 2023 in Madrid, the world’s premier medical oncology congress. In the ESMO (Free ESMO Whitepaper) scientific program, Optellum’s clinical partners will present the first results towards extending the LCP platform into AI-guided precision treatment in the "NSCLC, Early Stage".

The Eureka Clinical AI platform is renowned for its comprehensive suite of advanced imaging analytics, clinical decision support tools, and workflow optimization solutions. By being the first to integrate Optellum’s Virtual Nodule Clinic into the Eureka Clinical AI Platform, TeraRecon solidifies its position as a leader in transforming lung cancer care through innovative AI applications.

Eureka Clinical AI is the leading AI SaaS imaging interpretation and clinical decision augmentation solution from TeraRecon. As the industry’s most broadly deployed platform, it is unique in that it is open to third-party AI algorithms, allowing consolidated management of all AI interpretation solutions with seamless PACS integrations. Multi-specialty care teams can see results and receive mobile alerts to confirm AI findings, ensuring optimal and timely patient interventions, management and coordinated care delivery.

On October 17, 2023 Bio4t2 reported to have received regulatory approvals to repeatedly administer patients with T cells engineered to express a chimeric antigen receptor (CAR) targeting BT-001, an antigen on solid tumors identified using the PrismCore platform (Press release, Bio4T2, OCT 17, 2023, View Source [SID1234636085]). The CAR-T, termed B4t2-001, are predicted to engraft without preparative chemotherapy (lymphodepletion) based on the Bio-Engine technology enabling multiple infusions for each recipient to further improve the therapeutic effect.

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Clinical trial repeatedly infuses CAR-T without lymphodepletion to treat solid tumors.

Bio4t2, global clinical stage biopharmaceutical company combines PrismCore and Bio-Engine technologies to advance cutting-edge CAR-T therapy in phase 1 clinical trial.
Bio4t2, global clinical stage biopharmaceutical company combines PrismCore and Bio-Engine technologies to advance cutting-edge CAR-T therapy in phase 1 clinical trial.
The PrismCore platform generates CAR-T that recognizes overexpressed self-antigens on solid tumors. Bio-Engine adapts the CAR-T to transiently recognize a subset of circulating blood cells to boost the numbers of infused genetically modified T cells without the need for preparative chemotherapy. Bio4t2 harnesses these technologies to unlock the commercial potential of CAR-T in patients with invasive cancers.

A prior pilot investigator-initiated trial (clinicaltrials.gov NCT05621486) demonstrated that B4t2-001 can engraft to the range of 40 to 50% of circulating lymphocytes, even when lymphodepletion was omitted, and resulted in anti-tumor effects.

"This new phase 1 trial builds off our pilot clinical study which concluded a few weeks ago," said Dr. Laurence Cooper MD-PhD, Executive Chairman of the board. "Treating solid tumors depends on identifying targets that are uniformly expressed across cancer cells and engrafting CAR-T without immunological exhaustion. We combine our PrismCore and Bio-Engine technologies to achieve both goals and advance our cutting-edge CAR-T for the many patients with solid tumors," added Dr. Cooper.

"PrismCore identifies targets on invasive cancers and Bio-Engine harnesses normal blood cells to create a niche for CAR-T engraftment without the use of preparative chemotherapy," said Farzad Haerizadeh, PhD, Chief Scientific Officer, and co-founder. "Based on the success of our pilot clinical study, Bio4t2’s CAR-T is predicted to attack the tumor again and again without the cost, complexity, and toxicities, associated with lymphodepletion," said Haerizadeh.

About the clinical trial

The phase 1 investigator-initiated study (clinicals.gov NCT06072989) evaluates intra-patient repeat administration and inter-patient ascending doses of B4t2-001 targeting BT-001 without lymphodepletion in adult patients with solid tumors at Shanghai East and Shanghai Artemed hospitals in the People’s Republic of China. Furthermore, this trial assesses the safety, tolerability, pharmacokinetic, pharmacodynamic, and preliminary efficacy of autologous CAR-T.

On October 17, 2023 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a commercial stage biotechnology company, reported updated results from the KRYSTAL-7 Phase 2 study evaluating adagrasib combined with pembrolizumab in patients for the treatment of first-line NSCLC harboring a KRASG12C mutation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (ESMO) (Free ESMO Whitepaper) 2023 (Press release, Mirati, OCT 17, 2023, View Source [SID1234636084]). These data demonstrate a manageable safety profile and early signs of durability of adagrasib in combination with a checkpoint inhibitor in the first-line NSCLC setting.

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Summary of Clinical Results

In patients with PD-L1 TPS ≥50%, adagrasib and pembrolizumab demonstrated an overall response rate (ORR) of 63% and disease control rate (DCR) of 84% and promising early signs of durability. The 63% confirmed response rate compares favorably to pembrolizumab monotherapy which has demonstrated an ORR of 39-45%.1,2
A median progression free survival has not been reached at 10.1 months median follow up.
The safety profile of the adagrasib and pembrolizumab combination was consistent with either agent as monotherapy, with a low rate of treatment related adverse events (TRAEs) leading to discontinuation of both drugs in only 4% of patients.
Treatment related hepatic events occurred in <10% of patients and were predominantly low grade. No patients discontinued both adagrasib and pembrolizumab due to ALT/AST increase or hepatic-related TRAEs.
"Data presented to date indicate that adagrasib prescribed following or in combination with immunotherapy offers a tolerable safety regimen for first-line NSCLC patients with a KRASG12C mutation," said Marina C. Garassino, M.D., professor of medicine, UChicago Medicine. "Adagrasib is the only KRASG12C inhibitor to be feasibly combined concurrently or following immunotherapy with a well-managed hepatoxicity profile, and still exhibits positive efficacy signals."

"We are pleased to see these significant findings, which further support the initiation of a global Phase 3 study evaluating the combination of adagrasib plus immunotherapy in the first-line setting for KRASG12C-mutated NSCLC with PD-L1 TPS ≥50% for the benefit of patients," said Alan Sandler, M.D., chief medical officer, Mirati Therapeutics. "Potential combinability with an immunotherapy, in addition to encouraging clinical activity in other tumor types and demonstrated central nervous system (CNS) penetration, reinforces our confidence in the differentiation of adagrasib from other potential treatment options and the benefit it offers to patients."

Mirati plans to initiate a Phase 3 clinical study to evaluate adagrasib in combination with pembrolizumab in the first line setting for KRASG12C-mutated NSCLC with PD-L1 TPS ≥50%. Initial patient enrollment is expected by year-end 2023.

On October 17, 2023 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that the registrational Phase III study (HQP1351AG301, NCT06051409) of olverembatinib, Ascentage Pharma’s lead drug candidate, combined with chemotherapy, versus imatinib combined with chemotherapy in treatment-naïve patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has dosed its first patient (Press release, Ascentage Pharma, OCT 17, 2023, View Source [SID1234636083]). As a global best-in-class drug, olverembatinib holds the promise of becoming the first tyrosine kinase inhibitor (TKI) approved in China for the first-line treatment of Ph+ ALL.

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This global multi-center, randomized-controlled, open-label, registrational Phase III study (HQP1351AG301) is designed to evaluate the efficacy and safety of olverembatinib combined with chemotherapy versus imatinib combined with chemotherapy in newly-diagnosed patients with Ph+ ALL.

Accounting for 20%-30% of all ALL cases in adults, Ph+ ALL is commonly associated with a high relapse rate, short progression-free survival, and poor prognosis. Prior to the introduction of TKIs, a class of targeted small molecule compounds, allogeneic hematopoietic stem cell transplantation (allo-HSCT) after achieving complete responses (CRs) from chemotherapy was widely adopted as a first-line treatment for patients with Ph+ ALL. However, the five-year overall survival (OS) was only less than 30% and more than 70% patients relapsed before the transplantation or simply lacked access to the surgical treatment[1].

The clinical adoption of TKIs has resulted in a new clinical paradigm for patients with Ph+ ALL. However, first and second-generation TKIs have known clinical limitations, including high relapse rates and disappointing long-term survival with a three to five-year OS rate of just about 50%[2]. These limitations are primarily caused by low complete molecular responses (CMRs) and T315I kinase domain mutations, thus leaving substantial room for improvement in the treatment of Ph+ ALL. Currently, no TKI has been approved for the first-line treatment of Ph+ ALL in China and third-generation TKIs with more potent efficacy can potentially provide better prognosis to patients with Ph+ ALL by inducing a higher rate of CMRs and inhibiting the T315I mutation.

Ascentage Pharma’s novel drug candidate, olverembatinib, is an orally-administered third-generation TKI and the first and only China-approved third-generation BCR-ABL inhibitor. Currently, olverembatinib is being jointly commercialized by Ascentage Pharma and Innovent Biologics. In November 2021, Olverembatinib was approved by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) 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. Previously, olverembatinib received a recommendation from the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment Hematologic Malignancies as a treatment option for patients with Ph+ ALL.

(Olverembatinib is an investigational drug that has not been approved for any indication outside the Chinese mainland)

Prof. Weili Zhao, Vice President of Shanghai Jiaotong University School of Medicine Affiliated Ruijin Hospital and Director of Shanghai Institute of Hematology, commented, "Ph+ ALL used to be the most high-risk and difficult-to-treat subtype of leukemia and the introduction of TKIs has resulted in improved prognosis to patients with this condition. However, clinicians face the pressing question of which TKI offers the best efficacy and safety. We hope HQP1351AG301, a clinical study evaluating olverembatinib, a China-developed next-generation TKI, can provide an answer to those important questions."

Prof. Suning Chen, Deputy Director of the Hematology Department, the First Affiliated Hospital of Soochow University and Deputy Director of Jiangsu Institute of Hematology, noted, "Since its launch, olverembatinib showed excellent efficacy in patients with Ph+ ALL. We are very hopeful for the results from the HQP1351AG301 trial, as it is the first registrational clinical study for the first-line treatment of patients with Ph+ ALL."

Prof. Yang Shen, Deputy Director of the Hematology Department at Shanghai Jiaotong University School of Medicine Affiliated Ruijin Hospital, commented, "Olverembatinib has already been approved for the treatment of chronic myeloid leukemia in China. The HQP1351AG301 trial evaluates olverembatinib in Ph+ ALL, a potential additional indication in which olverembatinib has already showed promising therapeutic utility according to existing real-world data. We hope olverembatinib will offer a new treatment option to patients with Ph+ ALL."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "At present, the long-term survival rate of patients with Ph+ ALL remains disappointing, thus leaving considerable room for improvement. Multiple studies have shown that more potent third-generation TKIs can offer durable responses and a higher survival rate to patients with Ph+ ALL, yet no TKIs have been approved for the first-line setting in China. We are glad that this registrational Phase III study of olverembatinib, a TKI that could potentially become the first one approved in China for the first-line treatment of Ph+ ALL, has successfully enrolled and dosed its first patient. Moving forward, we will actively advance this clinical program and try to bring this drug to market as soon as possible for the benefit of more patients."