Chugai’s Alecensa Reduces the Risk of Disease Recurrence or Death by 76% in People with ALK-Positive Early-Stage Non-Small Cell Lung Cancer

On October 20, 2023 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported results from the primary analysis of the Phase III ALINA study of anti-cancer agent/ALK inhibitor Alecensa (alectinib), demonstrating a statistically significant and clinically meaningful improvement in disease-free survival (DFS; primary endpoint) (Press release, Chugai, OCT 20, 2023, View Source [SID1234636173]).

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The study results showed that Alecensa reduces the risk of disease recurrence or death by 76% (hazard ratio [HR]=0.24, 95% CI: 0.13-0.43, p<0.0001) compared with platinum-based chemotherapy in people with completely resected stage IB (tumour ≥4cm) to IIIA (UICC/AJCC 7th edition) anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).3 A clinically meaningful improvement of central nervous system (CNS)-DFS was also observed (HR=0.22; 95% CI: 0.08-0.58).3 The safety and tolerability of Alecensa in this trial were consistent with previous trials in the metastatic setting and no unexpected safety findings were observed.3 Overall survival data were immature at the time of this analysis and follow-up is ongoing.3

The full results of ALINA are being presented as a late-breaking oral at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 Presidential Symposium on Saturday 21 October 2023. These data will be submitted to global health authorities, including Japan, Europe, and the U.S.

"We are delighted that new data of Alecensa, a Chugai originated drug, was announced as the first ALK inhibitor to demonstrate a significant reduction in the risk of recurrence or death in early stage ALK-positive NSCLC in a Phase III study." said Dr. Osamu Okuda, Chugai’s President and CEO. "There is a significant need for adjuvant therapy to potentially cure early-stage NSCLC, which recurs in about half of patients. We are committed to collaborate with Roche towards submitting this data, which demonstrated Alecensa’s potential to become a new treatment option, to regulatory authorities around the world so that this drug can be delivered to patients as soon as possible."

Delaying disease progression is of particular importance for people with ALK-positive NSCLC, who are generally younger – usually around 55 – and are at higher risk of developing brain metastases than those with other types of NSCLC.4 Once the disease returns it often spreads to other parts of the body, at which point it is usually considered incurable.2,5 Comprehensive biomarker testing plays an important role in identifying the right treatment for each patient based on their genetic mutation.

Results from the primary analysis of the ALINA study showed that median DFS was not yet reached for Alecensa compared with 41.3 months for chemotherapy (95% CI: 28.5, not evaluable [NE]) in patients with stage IB (tumour ≥4cm) to IIIA disease.3 Grade 3 or 4 adverse events (AEs) occurred in 30% of people receiving Alecensa, compared with 31% of those receiving chemotherapy.3 No Grade 5 events were observed in either treatment arm.3 For those receiving Alecensa, 5.5% of patients discontinued treatment due to AEs versus 12.5% in the chemotherapy arm.3

About the ALINA study
The ALINA study [NCT03456076] is a Phase III, randomised, active-controlled, multicentre, open-label study evaluating the efficacy and safety of adjuvant Alecensa (alectinib) compared with platinum-based chemotherapy in people with completely resected stage IB (tumour ≥4cm) to IIIA (UICC/AJCC 7th edition) anaplastic lymphoma kinase (ALK)-positive NSCLC. The study includes 257 patients who were randomly assigned to either the investigational or control treatment arm. The primary endpoint is disease-free survival. Secondary outcome measures include overall survival and percentage of patients with adverse events.

About Alecensa
Alecensa is a highly selective, central nervous system-active, oral medicine created at Chugai, a member of the Roche Group, Kamakura Research Laboratories for people with non-small cell lung cancer (NSCLC) whose tumours are identified as anaplastic lymphoma kinase (ALK) positive. Alecensa is already approved in over 100 countries as an initial (first-line) and second-line treatment for ALK-positive, metastatic NSCLC, including in the United States, Europe, Japan and China. In Japan, Alecensa has also been approved for the treatment of recurrent or refractory ALK fusion gene-positive anaplastic large cell lymphoma.

About lung cancer
Lung cancer is one of the leading causes of cancer death globally.6 Each year 1.8 million people die as a result of the disease; this translates into more than 4,900 deaths worldwide every day.6 Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). NSCLC is the most prevalent type, accounting for around 85% of all cases.7 Today, about half of all people with early lung cancer (45-76%, depending on disease stage) still experience a cancer recurrence following surgery, despite adjuvant chemotherapy.1 Treating lung cancer early, before it has spread, may help prevent the disease from returning and provide people with the best opportunity for a cure.

BioCryst to Host R&D Day on November 3

On October 20, 2023 BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) reported that the company will host an R&D Day at 1:00 p.m. ET on Friday, November 3, 2023, where the company plans to describe its drug discovery process and introduce additional therapies from its pipeline (Press release, BioCryst Pharmaceuticals, OCT 20, 2023, View Source [SID1234636172]).

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The R&D Day will take place at the company’s Discovery Center of Excellence in Birmingham, Alabama. Seating for the event in Birmingham is limited to invited guests who have confirmed their attendance.

The event also will be webcast live. The live webcast and replay of the R&D Day will be available online in the investors section of the company website at www.biocryst.com.

AMGEN PRESENTS NEW TARLATAMAB DATA IN SMALL CELL LUNG CANCER

On October 20, 2023 Amgen (NASDAQ:AMGN) reported results from the global Phase 2 DeLLphi-301 study, evaluating tarlatamab, an investigational delta-like ligand 3 (DLL3) targeting BiTE (bispecific T-cell engager) molecule, in patients with advanced stage small cell lung cancer (SCLC) who had failed two or more prior lines of treatment (Press release, Amgen, OCT 20, 2023, View Source [SID1234636170]). The data are being presented today at 3:20 PM CEST at a Proffered Paper session as a late-breaking oral presentation (LBA92) during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 in Madrid, Spain, with publication in the New England Journal of Medicine.

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With a median follow-up of 10.6 months, an intention-to-treat analysis that included 100 patients at the selected 10 mg dose for tarlatamab demonstrated an objective response rate (ORR; primary endpoint) of 40% (97.5% Confidence Interval (CI): 29, 52). For key secondary endpoints, median progression-free survival (mPFS) was 4.9 months (95% CI: 2.9, 6.7) and median overall survival (mOS) was 14.3 months (95% CI: 10.8, NE). Median response duration was not reached. Of the patients who responded to treatment with tarlatamab at 10 mg dose, 58% experienced at least six months of response and 55% of responses were ongoing at data cutoff.

"Small cell lung cancer has represented one of the greatest challenges in cancer treatment, where there has been little progress against this deadly tumor type in decades," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "The tarlatamab results show the potential for this BiTE molecule in a common solid tumor. We look forward to discussing these potentially registrational data with regulatory authorities."

There were no new safety signals observed compared to Phase 1 study. Discontinuations due to treatment-related adverse events (TRAEs) were infrequent (4%). The most common treatment-emergent adverse events (TEAEs) reported among patients in the tarlatamab 10 mg group, were cytokine release syndrome (CRS; 49%), pyrexia (38%), decreased appetite (25%) and dysgeusia (24%). CRS was largely confined to the first and second dose, predominantly grade 1 or 2 and were generally managed with supportive care. At the tarlatamab 10 mg dose, grade 3 CRS was low (0%) and grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) and associated neurologic events were not observed (0%). There were no reported grade 4 or 5 cases for either of these two adverse events.

"In the current third-line treatment of SCLC, patients face a dire prognosis, with response rates ranging between 14 and 21 percent and median overall survival less than six months," said Luis Paz-Ares, M.D., Ph.D., chairman, Medical Oncology Department, Hospital Doce de Octubre; Head, Lung Cancer Unit, National Oncology Research Center (CNIO); associate professor, Universidad Complutense.

About Tarlatamab
Tarlatamab is an investigational, targeted immunotherapy engineered by Amgen researchers that brings a patient’s own T cells in close proximity to SCLC cells by binding both CD3 on T cells and DLL3 on SCLC cells. This results in the formation of an immunological synapse with lysis of the cancer cell.1,2 DLL3 represents an exciting therapeutic target for patients with SCLC, as approximately 85% to 94% of patients have expression of DLL3 on the cell surface of SCLC cells, with minimal expression in normal cells.3,4,5

In a Phase 1 study, tarlatamab showed responses in 23.0% of patients with encouraging durability in heavily pre-treated patients with SCLC.

Amgen is currently investigating tarlatamab in multiple trials, including DeLLphi-304, a Phase 3 study comparing tarlatamab versus standard of care chemotherapy in second-line treatment of SCLC that is enrolling patients. Amgen has plans to initiate two additional Phase 3 studies of tarlatamab in earlier settings of SCLC.

About Small Cell Lung Cancer (SCLC)
SCLC is one of the most aggressive and devastating solid tumors with a median survival of approximately 12 months following initial therapy and a 7% five-year relative survival rate across all stages 6,7,8 Of the 2.2M+ patients diagnosed with lung cancer worldwide each year, SCLC comprises 15% of cases.9,10

Despite initial high response rates to platinum-based first-line chemotherapy, patients quickly develop resistance to second-line and subsequent therapies and face a median time of survival of 10 to 12 months after diagnosis.11 Furthermore, there are currently no approved therapeutic options in the third-line treatment of SCLC.

About Tarlatamab Clinical Trials
Amgen’s robust tarlatamab development program includes the DeLLphi clinical trials, which evaluate tarlatamab as a monotherapy and as part of combination regimens in earlier stages of SCLC.

Tarlatamab is being investigated in multiple studies, including DeLLphi-301, a potentially registrational Phase 2 study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of tarlatamab in third-line or later relapsed/refractory SCLC.

Additional clinical studies underway include DeLLphi-302, a Phase 1b combination study evaluating tarlatamab in combination with an anti-PD-1 therapy in second-line or later SCLC; DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard of care therapies in first-line SCLC; and DeLLphi-304, a randomized Phase 3 trial comparing tarlatamab monotherapy with standard of care therapy in patients with SCLC who have relapsed following first-line platinum-based chemotherapy.12 Amgen also plans to initiate two additional Phase 3 studies of tarlatamab in earlier settings of SCLC.

For more information, please visit www.tarlatamabclinicaltrials.com.

About BiTE Technology
BiTE (bispecific T-cell engager) technology is a targeted immuno-oncology platform that is designed to engage patient’s own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing more than a dozen BiTE molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit View Source

Aixindawei will publish AST-3424 poster paper at ESMO 2023

On October 19, 2023 Shenzhen Ascentawits Pharmaceuticals , Ltd (hereinafter referred to as "Ascentawits" or "the Company") reported that the company will release the preclinical research results of AST-3424 for the treatment of tumors carrying DNA damage repair pathway gene mutations at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Conference held from the 20th to the 24th of this month, laying a solid foundation for the precision treatment of AST – 3424 (Press release, Ascentawits Pharmaceuticals, OCT 19, 2023, View Source [SID1234650304]) .

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Through theoretical innovation, the company has developed the world’s first innovative drugs at brand-new targets, and has reserved multiple candidate compounds on the two technology platforms of " AKR1C3 enzyme-activated prodrug" and "hypoxia-activated prodrug" with independent intellectual property rights, and has preliminarily determined the efficacy in clinical studies. Among them, the company’s first product AST-3424 is an AKR1C3-activated prodrug that releases a cytotoxic dialkylated group after being activated by tumor-specific AKR1C3. AST-3424 is currently undergoing Phase II clinical studies in China and the United States. In the poster paper published at this ESMO (Free ESMO Whitepaper) conference, we explored the important role of DNA repair in the in vitro and in vivo pharmacological activity mediated by AST-3424.

Dr. Duan Jianxin, Chairman of Aixindawei, pointed out that since its establishment, the company has always adhered to the principle of independent originality, and has developed new targets based on clinical needs. Among them, AST-3424 is a world-first targeted small molecule conjugated anti-cancer drug originally developed by our team. The current Phase II clinical trial is progressing smoothly. The research results released this time prove that DNA damage repair gene mutations play an important role in both the in vitro biological activity and in vivo anti-tumor activity mediated by AST-3424. The preclinical data provided in this study will provide important support for the company’s subsequent clinical exploration of new methods for treating cancer.

Poster presentation time : October 22 , 2023 ( Spanish time )

Poster title: 20P – The essential role of DNA repair in the pharmacological activities of AST-3424

Poster No.: 20 pages

Poster presenter: Meng Fanying Shenzhen Aixindawei Pharmaceutical Technology Co., Ltd.

Roche reports good sales growth despite decline in demand for COVID-19 products

On October 19, 2023 Hoffmann-La Roche reported its third quarter 2023 results (Presentation, Hoffmann-La Roche, OCT 19, 2023, View Source [SID1234638455]).

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