On September 23, 2024 Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd., reported the resubmission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for its investigational drug rivoceranib, an oral VEGF-TKI, in combination with camrelizumab, a PD-1 inhibitor, as a first-line systemic treatment option for unresectable hepatocellular carcinoma (uHCC) (Press release, Elevar Therapeutics, SEP 23, 2024, View Source [SID1234646816]).

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In May, the FDA issued a Complete Response Letter (CRL) for the original NDA submitted in May 2023. The CRL cited GMP deficiencies at the Hengrui Pharma facility where camrelizumab is manufactured and incomplete Bioresearch Monitoring (BIMO) clinical inspections due to FDA travel restrictions. The FDA did not indicate any issues related to clinical data or with the manufacturing site for rivoceranib. During a Type A meeting with the FDA in July, the FDA confirmed the responses to observations at the Hengrui manufacturing site were sufficient, resubmission could occur without further delay and BIMO inspections may occur after resubmission.

"Elevar’s timely resubmission of the NDA for the combination of camrelizumab and rivoceranib marks a critical milestone in our mission to bring a novel combination therapy for uHCC to patients and healthcare providers. HCC remains an area of significant unmet medical need," said Dr. Saeho Chong, chief executive officer of Elevar Therapeutics. "This achievement would not have been realized without the extraordinary dedication of Elevar’s teams. We are eager to work with the FDA in the coming months as we focus on the commercialization of our combination therapy." The resubmission is supported by the Phase 3 CARES-310 study landmark analysis presented during the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 1, which reported median overall survival (mOS) of 23.8 months, the longest mOS for any treatment in a global Phase 3 trial for patients with uHCC, confirming the combination of camrelizumab and rivoceranib continued to show sustained long-term survival as a first-line treatment for uHCC.

"The combination of camrelizumab and rivoceranib shows distinct promise as a potential therapy for patients suffering from advanced hepatocellular carcinoma with efficacy results generally consistent across all subgroups," commented Ahmed Omar Kaseb, M.D., professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston. "The resubmission is strengthened by the recent CARES-310 landmark analysis, which reported the longest median overall survival for any treatment in a global Phase 3 trial in the uHCC setting."

About Hepatocellular Carcinoma

Worldwide each year more than 800,000 people are diagnosed with liver canceri and the disease is the cause of more than 830,000 deaths.ii Hepatocellular Carcinoma (HCC) is the most common type of liver cancer and most frequently develops in people with chronic underlying liver inflammation which may be from viral and non-viral causes. HCC typically has a poor prognosis with limited treatment options and continues to be a diagnosis with an ongoing urgent medical need.

About Rivoceranib

Rivoceranib, a small-molecule tyrosine kinase inhibitor (TKI), is a highly potent inhibitor of vascular endothelial growth factor receptor (VEGFR), a primary pathway for tumor angiogenesis. VEGFR inhibition is a clinically validated target to limit tumor growth and disease progression. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Ongoing clinical studies include uHCC (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf). Rivoceranib was the first TKI approved in gastric cancer in China (November 2014). It is also approved in China in combination with camrelizumab as a first-line treatment for uHCC (January 2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in uHCC (U.S. and EU). Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is also approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese -territory license-holder, Jiangsu Hengrui Pharmaceuticals Company Ltd., (Hengrui Pharma), under the brand name Aitan.

About Camrelizumab

Camrelizumab (SHR-1210) is a humanized monoclonal antibody that binds to the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Camrelizumab is developed by Hengrui Pharma and has been studied in more than 5,000 patients. Currently, 50 clinical trials are underway in a broad range of tumors (including liver cancer, lung cancer, gastric cancer, and breast cancer, etc.) and treatment settings. Camrelizumab, under the brand name AiRuiKa, is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), in combination with rivoceranib as a treatment for uHCC (first-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma and nasopharyngeal carcinoma in the first-line setting. The U.S. Food and Drug Administration granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021 and by the EMA in August 2024.

In October 2023, Elevar licensed camrelizumab, an anti-PD-1 antibody, for commercialization from Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Hengrui Pharma) worldwide excluding Greater China and Korea.

On September 23, 2024 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of emavusertib (CA-4948), an orally available, small molecule IRAK4 inhibitor, reported the 3rd Annual Symposium on IRAK4 in Cancer taking place virtually on September 26, 9:00 AM-1:00 PM E.T (Press release, Curis, SEP 23, 2024, View Source [SID1234646815]).

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Hosted by Dr. Eric S. Winer (Dana-Farber Cancer Institute) and Dr. Grzegorz S. Nowakowski (Mayo Clinic Comprehensive Cancer Center), this symposium will focus on IRAK4, an emerging target in the treatment of hematologic malignancies and solid tumors. Experts will discuss the promise of IRAK4 inhibition in cancer, including current clinical studies of emavusertib and opportunities for future development.

Symposium presentations will include updated data for 10 evaluable R/R PCNSL patients as of the July 10, 2024 cutoff date. The Company continues to enroll patients in the PCNSL study and is on track to enroll 15-20 patients by year-end.

"As the leader in IRAK4 inhibition in oncology with emavusertib, we are honored to provide a forum for discussing the biology of the IRAK4 pathway and IRAK4 inhibition in the research and development of therapies to benefit patients living with cancer," said James Dentzer, President, and Chief Executive Officer of Curis.

Symposium co-chairs:

Eric Winer, MD, Clinical Director and Adult Leukemia Institute Physician, Dana-Farber Cancer Institute; Assistant Professor of Medicine, Harvard Medical School
Grzegorz Nowakowski, MD, Professor of Oncology and Medicine, Division of Hematology, Deputy Director of Mayo Clinic Comprehensive Cancer Center for Clinical Research and Vice-Chair of Division of Hematology
Joining our hosts will be the following speakers and participants:

Bently Doonan, MD, Assistant Professor, Division of Hematology and Oncology, University of Florida College of Medicine
Andrés Ferreri, MD, Contract Professor of Oncology, University Vita-Salute San Raffaele; Head of the Lymphoma Unit, I.R.C.C.S. Ospedale San Raffaele
Klaus Metzeler, MD, Professional of Translational Hematology, University of Leipzig
Guillermo Garcia-Manero, MD, Professor, Chief of Section of Myelodysplastic Syndromes, Deputy Chair of Translational Research and Fellowship Program Director Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
Marina Konopleva, MD, PhD, Professor of the Department of Oncology, Professor of the Department of Molecular Pharmacology, and Miriam Mandel Faculty Scholar in Cancer Research, Albert Einstein College of Medicine
Kian Lim, MD, PhD, Associate Professor, Department of Medicine, Division of Oncology, Washington University School of Medicine in St. Louis
Lakshmi Nayak, MD, Director of the Center for CNS Lymphoma Dana‑Farber Cancer Institute; Associate Professor of Neurology, Harvard Medical School
Han Tun, MD, Hematologist, Internist, Oncologist, Departments of Hematology and Mayo Clinic Comprehensive Cancer Center
To learn more about this free-to-attend symposium and register, please visit View Source

On September 23, 2024 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, reported initial Phase 2 data demonstrating encouraging clinical responses and durability of BDTX-1535 in patients with relapsed/refractory epidermal growth factor receptor (EGFR)-mutant (EGFRm) non-small cell lung cancer (NSCLC) (Press release, Black Diamond Therapeutics, SEP 23, 2024, View Source [SID1234646811]).

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"Patients often become resistant to osimertinib with the emergence of on-target resistance EGFR mutations," said Sergey Yurasov, M.D., Chief Medical Officer of Black Diamond Therapeutics. "Our preliminary Phase 2 data demonstrate the potential of BDTX-1535 to deliver durable responses for these patients."

"Patients with recurrent EGFRm NSCLC have few treatment options, with chemotherapy delivering limited benefit and significant toxicity, and initial Phase 2 data with BDTX-1535 look quite promising," said Danny Nguyen, M.D., Assistant Clinical Professor, Department of Medical Oncology and Therapeutics Research at City of Hope. "There is a significant unmet medical need for an effective and well-tolerated oral therapy for patients who progress on osimertinib, as well as newly diagnosed patients with non-classical mutations."

Phase 2 preliminary data overview:

The phase 2 trial began in August of 2023, and enrolled relapsed/refractory patients with non-classical EGFR mutations (NCMs) (Cohort 1) and those with C797S resistance mutations (Cohort 2). Safety assessment and dose selection were based upon the first 40 patients randomized to receive BDTX-1535 once daily at either 100 mg or 200 mg across both Cohorts. Preliminary response rate and durability were assessed in 27 patients at 200 mg with an August 17, 2024, data cutoff, including 22 response-evaluable patients who met protocol eligibility criteria.

Key takeaways:

200 mg daily selected for pivotal clinical development. Dose selection was based primarily on pharmacokinetics, safety and tolerability data from 20 patients at 100 mg, and 20 patients at 200 mg.
Favorable tolerability profile at 200 mg, consistent with prior BDTX-1535 clinical data. The majority of adverse events were mild or moderate, and no new safety signals were observed. The most common on-target treatment-related adverse events were rash (70%) and diarrhea (35%). There were 2 cases of grade 3 rash, and no reported cases of grade 4 rash or grade 3/4 diarrhea.
Preliminary objective response rate (ORR) of 42% achieved in 19 patients. For the 22 response-evaluable patients, the preliminary ORR was 36%. Nineteen of these 22 patients expressed known osimertinib resistance mutations: either C797S or P-loop alpha-C helix compressing (PACC, a major subset of NCMs). Of these 19 patients, 8 achieved a response (42%): 5 with a confirmed partial response (PR), including 1 patient who converted from a PR to an unconfirmed complete response (CR) at 8 months (and awaits confirmatory scan); and 3 with an unconfirmed PR at first scan and awaiting a confirmatory scan. An additional 9 patients experienced stable disease.
Encouraging durability observed, with duration of response (DOR) of approximately 8 months or more for first 3 patients with PR; 14 of 19 patients remain on therapy. Mean follow-up time is 4.7 months.
"We are pleased to see significant Phase 2 clinical activity and tolerability that are consistent with our Phase 1 results," said Mark Velleca, M.D., Ph.D., Chief Executive Officer of Black Diamond Therapeutics. "We believe that the activity observed in the recurrent setting can translate to robust clinical benefit in the first-line setting, and we look forward to sharing data from our trial in newly diagnosed patients in Q1 2025."

Black Diamond continues to enroll patients in the second- and third-line cohorts, as well as in the first-line setting for patients with non-classical EGFR mutations. In Q1 2025, the Company expects to disclose initial results from the first-line cohort and to outline potential registrational paths in the recurrent setting based on FDA feedback.

About BDTX-1535

BDTX-1535 is an oral, brain-penetrant MasterKey inhibitor of oncogenic EGFR mutations in NSCLC, including classical driver mutations, non-classical driver mutations, and the acquired resistance C797S mutation. BDTX-1535 is a fourth-generation tyrosine kinase inhibitor (TKI) that potently inhibits, based on preclinical data, more than 50 oncogenic EGFR mutations expressed across a diverse group of patients with NSCLC in multiple lines of therapy. Based on preclinical data, BDTX-1535 also inhibits EGFR extracellular domain mutations and alterations commonly expressed in glioblastoma (GBM) and avoids paradoxical activation observed with earlier generation reversible TKIs. A "window of opportunity" trial of BDTX-1535 in patients with GBM is ongoing (NCT06072586) and a Phase 2 trial is ongoing in patients with NSCLC (NCT05256290).

On September 22, 2024 Adaptimmune Therapeutics plc (the "Company") reported to have entered into a Mutual Release and Resolution Agreement (the "Agreement") with Genentech Inc and F. Hoffmann-La Roche Ltd, (together "Genentech") (Filing, Adaptimmune, SEP 23, 2024, View Source [SID1234646808]). The parties entered into the Agreement following notice of termination of their Collaboration and License Agreement dated September 3, 2021 (the "Collaboration Agreement") on April 8, 2024 in order to, among other things, resolve and release each party from any and all past, present and future disputes, claims, demands and causes of action, whether known or unknown, related to the Collaboration Agreement in any way. Under the terms of the Agreement, Genentech will pay the Company $12,500,000, and the Collaboration Agreement will be terminated. The Agreement is effective as of September 23, 2024 following which each party to the Agreement is expressly released from any and all past, present and future disputes, claims, demands and causes of action, whether known or unknown, related to the Collaboration Agreement in any way.

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The foregoing description of the Agreement is only a summary of certain material terms thereof, and does not purport to be complete. The description is qualified in its entirety by reference to the complete text of the Agreement to be filed with the Securities and Exchange Commission in connection with the Company’s Form 10-Q for the quarter ended September 30, 2024.

On September 23, 2024 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), reported that the Company’s Phase 2a clinical trial investigating narmafotinib in the treatment of advanced pancreatic cancer (the ACCENT trial) has achieved the required response rate to support continued enrolment in the study (Press release, Amplia Therapeutics, SEP 23, 2024, View Source [SID1234646785]). Six (6) patients have now recorded confirmed partial responses (PRs) out of 16 assessed at the four-month timepoint, indicating that the combination of narmafotinib with the chemotherapies gemcitabine and Abraxane is sufficiently active to support continuation of the trial.

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The formal term ‘confirmed partial response’ means in these patients there is at least a 30% decrease in the overall size of tumour lesions, with no new tumour lesions, sustained over a two-month period.

A total of 50 patients are planned for the Phase 2a ACCENT trial. With the six (6) confirmed PRs now obtained, recruitment of the remaining 24 patients in the trial will begin at the existing open trial sites in Australia and South Korea. Recruitment of the second cohort of patients is expected to be completed by end of Q1 2025.

A detailed interim analysis of the Phase 2a trial data obtained to date will be reported in the coming weeks; however, key points are noted below: • Narmafotinib continues to be generally well tolerated by patients with no safety trends identified or dose reductions recorded to date • In addition to 6 confirmed PRs, there have been 7 patients who have recorded stable disease over 2 or more months, including one patient whose stable disease has improved to achieve a partial response at their 4-month assessment

Amplia CEO and MD Dr Chris Burns commented: "Having now confirmed our sixth PR, we will move forward with recruiting the remaining 24 patientsfor the trial. We are actively working with our clinical sites to ensure seamless reopening of enrolment with the goal of completing recruitment by the end of March 2025. As always, we thank the patients and their loved ones for being involved with this trial"

About Narmafotinib

Narmafotinib (AMP945) is the company’s best-in-class inhibitor of the protein FAK, a protein overexpressed in pancreatic and other cancers, and a drug target gaining increasing attention for its role in solid tumours. The drug, which is a highly potent and selective inhibitor of FAK, has shown promising data in a range of preclinical cancer studies. The drug has successfully completed a healthy volunteer study, and is currently in an open-label Phase 2a trial in pancreatic cancer where a combination of narmafotinib and the chemotherapies gemcitabine and Abraxane is being assessed for safety, tolerability and efficacy.

About the ACCENT Trial

The ACCENT trial is entitled ‘A Phase 1b/2a, Multicentre, Open Label Study of the Pharmacokinetics, Safety and Efficacy of AMP945 in Combination with Nab-paclitaxel and Gemcitabine in Pancreatic Cancer Patients’.

The ACCENT trial explores the use of narmafotinib in combination with standard-of-care chemotherapy of gemcitabine and Abraxane in first-line patients with advanced pancreatic cancer. The trial is a single-arm open label study conducted in two stages. The firststage (Phase 1b), completed in November 2023, identified a 400 mg oral daily dose of narmafotinib, given in the days preceding regular chemotherapy infusion, as safe and well tolerated.

This second stage (Phase 2a), of the trial is designed to assess drug efficacy in combination with gemcitabine and Abraxane. The primary endpoints are Objective Response Rate (ORR) and Duration on Trial (DOT) with secondary endpoints being Progression Free Survival (PFS) and Overall Survival (OS). Safety and tolerability will continue to be assessed.

More information about the ACCENT trial, including a list of participating sites, can be found via the Amplia Therapeutics website and at ClinicalTrials.gov under the identifier NCT05355298.