Chugai Submits Application in Japan for Tecentriq as First Adjuvant Immunotherapy to Significantly Prolong Disease-Free Survival in Resectable Early-Stage Lung Cancer

July 18, 2021 /BioonBIOON/ -- Chugai Pharmaceutical Co., Ltd. (Chugai Pharma), a Japanese pharmaceutical company controlled by Roche, recently announced that it has submitted a regulatory application to the Japanese Ministry of Health, Labour and Welfare (MHLW) for the anti-PD-L1 therapy Tecentriq (atezolizumab) for the adjuvant (post-operative) treatment of patients with non-small cell lung cancer (NSCLC).

This application is based on the results of the Phase III IMpower010 study, with relevant data published in May this year. The data show that,Among all randomized patients with stage II–IIIA NSCLC, adjuvant Tecentriq following surgery and chemotherapy reduced the risk of disease recurrence or death by 21% compared with best supportive care (BSC).(Disease-free survival, PFS; HR = 0.79, 95% CI: 0.64, 0.96).In# TumorIn patients with stage II–IIIA NSCLC expressing PD-L1 (≥1%), Tecentriq demonstrated more pronounced efficacy, reducing the risk of disease recurrence or death by 34%.(HR = 0.66, 95% CI: 0.50–0.88). In this study, the safety data for Tecentriq were consistent with its known safety profile, with no new safety signals identified. In this study, PD-L1 expression was assessed using the VENTANA OptiView PD-L1 (SP142) assay, which is RocheDiagnosisA pathology testing kit sold by the company (Roche Diagnostics K.K.).

IMpower010 is the first phase 3 study to demonstrate that a cancer immunotherapy improves disease-free survival (DFS) compared with best supportive care (BSC) in patients with resectable early-stage lung cancer. Meanwhile,Tecentriq is the first cancer immunotherapy to achieve positive Phase III results in the adjuvant treatment of early-stage lung cancer.

The purpose of adjuvant therapy is to reduce the risk of recurrence and provide the best chance for a cure. Nevertheless, approximately half of patients with stage I–III NSCLC will eventually experience disease recurrence following curative-intent treatment. Adjuvant platinum-based chemotherapy is currently the standard of care for patients with early-stage NSCLC (stage IB–IIIA) at high risk of disease recurrence after complete resection. Compared with observation, adjuvant platinum-based chemotherapy confers a modest 4–5% improvement in 5-year survival rates. Consequently, there remains a significant unmet medical need for novel adjuvant treatment regimens in this field.

Dr. Osamu Okuda, President and Chief Executive Officer of Chugai Pharmaceutical Co., Ltd., stated: “Approximately 50% of patients with early-stage lung cancer experience recurrence after surgery. Preventing recurrence is crucial to improving cure rates. Tecentriq is the first cancer immunotherapy to reduce the risk of disease recurrence or death in NSCLC when used as adjuvant therapy following surgery. We are working diligently to obtain regulatory approval to make Tecentriq available to patients as soon as possible as a new adjuvant treatment for early-stage lung cancer, which has been proven to reduce the risk of recurrence or death.”

IMpower010 Clinical Data (Click image to view larger version)

IMpower010 is a global, multicenter, open-label, randomized phase 3 study evaluating the efficacy and safety of adjuvant treatment with Tecentriq versus BSC in patients with stage IB-IIIA NSCLC (UICC 7th edition) following surgical resection and up to 4 cycles of platinum-based adjuvant chemotherapy. In this study, 1,005 patients were randomized 1:1 to receive up to 16 cycles of Tecentriq or BSC. The primary endpoint was investigator-assessed disease-free survival (ivDFS) in the PD-L1-positive stage II-IIIA population, all randomized stage II-IIIA population, and the intention-to-treat (ITT) stage IB-IIIA population. Key secondary endpoints included overall survival (OS) in the overall study population and the ITT stage IB-IIIA NSCLC population. Results showed:

——In`Tumor`In patients with stage II-IIIA NSCLC and PD-L1 expression ≥1%: following surgery and chemotherapy, adjuvant therapy with Tecentriq significantly reduced the risk of disease recurrence or death by 34% compared with BSC.(HR = 0.66; 95% CI: 0.50–0.88; p = 0.004). In this patient population, the median DFS in the Tecentriq treatment group was not reached, while the median DFS in the BSC group was 35.3 months.

——In all randomized stage II–IIIA NSCLC patients: After a median follow-up of 32.2 months, Tecentriq reduced the risk of disease recurrence or death by 21% compared with BSC.(HR=0.79; 95% CI: 0.64-0.96; p=0.02). In this patient population, compared with the BSC group, the median DFS in the Tecentriq group was prolonged by 7 months (42.3 months vs 35.3 months).

In this study, the safety data for Tecentriq were consistent with its known safety profile, with no new safety signals identified. Across the overall study population, adverse events (AEs) occurred in 92.7% of patients in the Tecentriq group and 70.7% in the BSC group; Grade 3 or 4 AEs occurred in 21.8% of patients in the Tecentriq group and 11.5% in the BSC group. Grade 5 AEs occurred in 0.8% of patients in the Tecentriq group. As expected, when administered as adjuvant therapy for up to one year following chemotherapy, Tecentriq resulted in a higher incidence of adverse events compared with BSC.

Follow-up will continue in this study to allow for a planned analysis of DFS in the entire intention-to-treat (ITT) population, including stage IB patients, whose data had not yet reached the threshold at the time of this analysis; at the interim analysis, overall survival (OS) data were not yet mature.

Lung cancer is the leading cause of cancer mortality worldwide. Approximately 1.76 million people die from the disease annually, translating to more than 4,800 deaths globally each day. Lung cancer can be broadly classified into two main categories: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most common type, accounting for approximately 85% of all cases. Currently, roughly half of patients with early-stage lung cancer still experience cancer recurrence following surgery. Early treatment before the cancer spreads may help prevent disease recurrence and provide patients with the optimal chance of a cure.

Previously, Tecentriq has demonstrated clinically meaningful benefits across various types of lung cancer and has been approved for multiple indications in lung cancer: (1) Tecentriq is the first cancer immunotherapy approved for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC), in combination with chemotherapy (carboplatin plus etoposide); (2) it holds four approved indications for the treatment of NSCLC, as monotherapy or in combination with targeted therapy and/or chemotherapy. Tecentriq offers three dosing regimens, allowing flexible administration every 2, 3, or 4 weeks.

Tecentriq is a PD-(L)1 tumor immunotherapy that targets and binds to tumor cells andTumorBinds to PD-L1, a protein expressed on tumor-infiltrating immune cells, blocking its interaction with PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq can activate T cells. The drug has the potential to serve as a backbone combination therapy for cancer immunotherapies, targeted therapies, and various chemotherapy regimens.

To date, Tecentriq has been approved in the United States, the European Union, and other countries worldwide as a monotherapy, and in combination with targeted therapy and/or chemotherapy, for the treatment of various types of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), certain types of metastatic urothelial carcinoma (mUC), and PD-L1-positive metastatic triple-negativeBreast Cancer(mTNBC), hepatocellular carcinoma (HCC). In the United States, Tecentriq is also approved in combination with Cotellic (cobimetinib) and Zelboraf (vemurafenib) for the treatment of advanced BRAF V600 mutation-positiveMelanoma。

Roche has established an extensive development program for Tecentriq, encompassing multiple ongoing and planned Phase III studies across various types of lung, genitourinary, skin, breast, gastrointestinal, gynecological, and head and neck cancers. This includes studies evaluating Tecentriq as monotherapy or in combination with other therapeutic agents. (Bioon.com)

Source:Chugai Files for Additional Indication of Tecentriq for the Adjuvant Treatment of Non-small Cell Lung Cancer