On June 23, 2021 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has obtained manufacturing and marketing approval for the EZH2 inhibitor "Tazverik Tablets 200 mg" (tazemetostat hydrobromide) in Japan with the indication of relapsed or refractory EZH2 gene mutation-positive follicular lymphoma (only when standard treatment is not applicable) (Press release, Eisai, JUN 23, 2021, View Source [SID1234584266]).

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This approval is based on the results of a multicenter, open-label, single-arm clinical phase II trial (Study 206)1 in Japan conducted by Eisai and other studies2 conducted by Epizyme, Inc. (Headquarters: Massachusetts, United States) outside Japan. Study 206 enrolled patients with EZH2 gene mutation-positive, primarily follicular lymphoma, who had relapsed or were refractory. The primary endpoint of this study was objective response rate (ORR), and secondary endpoints included safety. This study achieved the primary endpoint target and exceeded a prespecified tumor response threshold with statistical significance: ORR in patients with EZH2 mutation-positive relapsed or refractory follicular lymphoma (n=17) was 76.5% (90% confidence interval (CI): 53.9-91.5) as measured by independent review. Treatment-emergent adverse events (incidence of 25% or more) observed in this study were dysgeusia (52.9%), nasopharyngitis (35.3%), lymphopenia (29.4%) and blood creatine phosphokinase increased (29.4%). Eisai will conduct a post-marketing special use results survey (all-case surveillance) in all patients who are administered "Tazverik" until a pre-determined number of patients has been reached in accordance with an approval condition imposed by the MHLW.

Created by utilizing Epizyme’s proprietary product platform, "Tazverik" is a first-in-class small molecule inhibitor of the epigenetic enzyme EZH2. It is one of the histone methyltransferases in the epigenetics-related protein group, and is thought to regulate the expression of cancer-related genes and suppress the growth of cancer cells by specifically targeting EZH2, which contributes to the cancer growth process.3 Eisai is responsible for the development and commercialization of this agent in Japan, while Epizyme, Inc. is responsible for all regions outside of Japan. In the United States, "Tazverik" received accelerated approval for the indication of epithelioid sarcoma in January 2020, and follicular lymphoma in June 2020 (Notes to editors 1).

Follicular lymphoma is a low-grade B-cell lymphoma that accounts for 10-20% of non-Hodgkin’s lymphomas. Follicular lymphoma is generally indolent and sensitive to chemotherapy. However, development of a new treatment strategy is required for follicular lymphoma which still remains difficult to cure, as recurrence often occurs repeatedly. 7-27% of follicular lymphomas are reported to have gain-of-function mutations in the EZH2 gene,4,5 and it is estimated that there are approximately 600 to 2,400 patients with follicular lymphoma with EZH2 gene mutations in Japan. A companion diagnostic test for EZH2 gene mutations, "cobas EZH2 Mutation Test" by Roche Diagnostics K.K. (Headquarters: Tokyo) was approved in May 2021.
　

Eisai aims to make continuous efforts to meet the diversified needs of and increase the benefits provided to patients with cancer, their families, and healthcare professionals, by delivering "Tazverik" as a new treatment option for EZH2 gene mutation-positive follicular lymphoma.

On June 23, 2021 AstraZeneca and HUTCHMED reported that its Orpathys (savolitinib) has been granted conditional approval in China to treat patients with non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy (Press release, AstraZeneca, JUN 23, 2021, View Source [SID1234584265]).

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This approval follows a priority review designation by the Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) and marks the first global regulatory approval for the oral, potent, and highly selective MET tyrosine kinase inhibitor (TKI).

More than a third of the world’s lung cancer patients are in China and, among those with NSCLC, approximately 2-3% have tumours with MET exon 14 skipping alterations, a targetable mutation in the MET gene.1-3 This mutation is more common (13-22%) among patients with pulmonary sarcomatoid carcinoma (PSC), a rare and aggressive subtype of NSCLC usually resistant to chemotherapy.1,4

The approval by the NMPA was based on positive results from a single-arm Phase II trial conducted in China in patients with NSCLC with this mutation, including patients with the PSC subtype. Orpathys demonstrated robust anti-tumour activity based on an independent review of objective response rate (ORR) in the trial’s primary endpoint and its disease control rate (DCR). Continued approval is contingent upon the successful completion of a confirmatory trial in this patient population.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "This approval makes Orpathys the only targeted medicine approved for these biomarker-selected patients in China, and it adds another novel medicine to our already diverse lung cancer portfolio. We are proud that this first-ever regulatory approval of Orpathys is in China, where we have a long-standing commitment to improving patient outcomes and working with the right partners to achieve that goal. Alongside HUTCHMED, we look forward to the continued development of this medicine across a range of cancers where MET alterations and amplification are drivers of tumour growth and treatment resistance."

Christian Hogg, Chief Executive Officer, HUTCHMED, said: "It is with great pleasure that today we announce the first regulatory approval of Orpathys globally, HUTCHMED’s third self-discovered oncology drug to be commercialized. Our collaboration with AstraZeneca in 2011 has been an important driver in the development of this novel targeted oncology drug, involving both a China-based biotech and a global pharmaceutical company. This approval is a testament to the perseverance and scientific ingenuity of this long-standing alliance, and we are hopeful that this is only the beginning of the progress we can achieve for patients with MET-altered tumours."

In the Phase II trial, at a median follow up of 17.6 months, Orpathys demonstrated an ORR of 42.9% (95% confidence interval [CI] 31.1-55.3) and median progression-free survival (PFS) of 6.8 months (95% CI 4.2-9.6) in the overall trial population. PFS was clinically meaningful across subgroups, and ORR results were consistent regardless of prior treatment or tumour histology, including in patients with the PSC subtype (40.0%, 95% CI 21.1-61.3) and patients with other NSCLC subtypes (44.4%, 95% CI 29.6-60.0). DCR in the overall trial population was 82.9% (95% CI 72.0-90.8).

The safety and tolerability profile of Orpathys was consistent with previous trials, and no new safety signals were identified. Most adverse events (AEs) were Grade 1–2 and resolved with dose modification or discontinuation. Grade 3 or higher AEs occurred in 45.7% of patients, and treatment-related serious AEs occurred in 24% of patients. One treatment-related death was reported from tumour lysis syndrome in a patient with PSC.

Results from the Phase II trial were presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program in May 2020, and updated results were published in The Lancet Respiratory Medicine in June 2021.

As part of the joint global development programme with HUTCHMED, Orpathys is being evaluated in combination with Tagrisso and other medicines to address tumour mechanisms of resistance in NSCLC in the ORCHARD and SAVANNAH Phase II trials for the combinations to provide longer duration of benefit, and as a treatment for other MET-driven tumours, including papillary renal cell carcinoma, and gastric and gastroesophageal junction cancers.

NSCLC, PSC and MET aberrations
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.2 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.5 The majority of NSCLC patients are diagnosed with advanced disease.6

PSC is a rare subtype of NSCLC, comprising 0.3-3% of all lung malignancies.7 Compared with other NSCLC subtypes, PSC patients have a poorer prognosis and limited treatment options.4,8-9

MET is a tyrosine kinase receptor.10 While MET genetic alterations are common in many solid tumours, MET exon 14 skipping alterations are more frequently associated with lung cancer, occurring in approximately 2-3% of patients with NSCLC and 13-22% of patients with PSC.1,4,11 MET amplification or overexpression is one of the mechanisms of acquired resistance to epidermal growth factor receptor (EGFR) TKIs for metastatic EGFR-mutated NSCLC.10

NCT02897479
The single-arm, open-label Phase II trial NCT02897479 assessed the efficacy and safety of Orpathys in the treatment of Chinese patients with locally advanced or metastatic PSC or other NSCLC subtypes with MET exon 14 skipping alterations who progressed on prior treatment or were unable to receive chemotherapy.

Patients were treated with weight-based dosing of Orpathys once-daily oral tablets (600mg/day or 400mg/day for patients weighing less than 50kg). Treatment continued until disease progression, death, intolerable toxicity, or discontinuation. The trial enrolled 70 patients across multiple centres in China. The primary endpoint was ORR, and key secondary endpoints were PFS, DCR and safety assessment.

Orpathys
Orpathys (savolitinib) is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumours. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations) or gene amplification.

Orpathys is currently under clinical development for multiple tumour types, including lung, kidney, and gastric cancers, as a single treatment and in combination with other medicines.

AstraZeneca and HUTCHMED collaboration
In 2011, AstraZeneca and HUTCHMED entered a global licensing agreement to jointly develop and commercialise Orpathys. HUTCHMED is responsible for the manufacturing and supply of Orpathys, and AstraZeneca is responsible for its commercialisation in China and worldwide. Sales of Orpathys will be recognised by AstraZeneca.

AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and assessing innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and tremelimumab; Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On June 23, 2021 XBiotech Inc. (NASDAQ: XBIT) reported that it has enrolled the first patient in its 1-BETTER study, a randomized, double-blind, placebo-controlled clinical study to evaluate XB2001 in combination chemotherapy for treatment of Pancreatic Cancer (Press release, XBiotech, JUN 23, 2021, View Source [SID1234584263]).

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XBiotech’s novel anti-cancer agent, XB2001, is being assessed in combination with ONIVYDE + 5-FU/LV chemotherapy regimens. Safety and tolerability of the regimen, as well as progression-free survival, overall survival and time-to-treatment-failure will be assessed in the study.

XB2001 blocks inflammation pathways turned on by tumors that help tumors vascularize, spread and cause collateral damage to healthy tissues. By using XB2001 to block inflammation in pancreatic cancer, investigators also hope to see a reduction in serious adverse events and reduced hospitalizations of subjects. Moreover, the anti-inflammatory effects of XB2001 may make the chemotherapy more effective and less toxic.

The study is also investigating a novel clinical endpoint that XBiotech calls the "clinical benefit response", which involves radiological assessment of muscle mass and patient reported measures of pain, fatigue and appetite. In earlier clinical studies in advanced cancer patients, XBiotech discovered that subjects with preserved muscle mass and stabilization or improvement of these symptoms, had dramatically improved overall survival. The Company previously validated this endpoint in a phase III study in colorectal cancer patients and will explore this endpoint now with its new drug in pancreatic cancer.

The current study will commence with a Phase 1 portion to establish safety, tolerability and dosing of XB2001 in combination with ONIVYDE+5-FU/LV. The Phase I portion will serve to establish a recommended Phase 2 dose, which will involve enrollment of 60 patients randomized to receive either placebo+ONIVYDE+5-FU/LV or XB2001+ONIVYDE+5-FU/LV for up to 12 cycles.

Dr. Carl Gray, Principal Investigator at Community Cancer Trials of Utah, site of first patient enrollment, commented, "Pancreatic cancer remains an aggressive and difficult form of cancer to treat. If we can use XB2001 to improve outcomes and increase the tolerability of chemotherapy, this would be an exciting advance."

John Simard, chairman and CEO of XBiotech stated, "Chemotherapy and paraneoplastic-related acute and chronic inflammatory responses play a key role in tumor progression and is a cause of significant morbidity with chemotherapy. Currently there is no approved therapy to specifically target this fundamental aspect of tumor biology or these effects of chemotherapy."

About True Human Therapeutic Antibodies
XBiotech’s True Human antibodies are derived without modification from individuals who possess natural immunity to certain diseases. XBiotech is undertaking discovery and clinical development programs across multiple disease areas. XBiotech’s True Human antibodies have the potential to harness the body’s natural immunity to fight disease with increased safety, efficacy and tolerability.

On June 23, 2021 Clovis Oncology, Inc. (NASDAQ: CLVS), reported that the first clinical site for the Phase 1/2 LuMIERE study of FAP-2286, its novel peptide-targeted radionuclide therapy and imaging agent targeting fibroblast activation protein (FAP), is now open at the O’Neal Comprehensive Cancer Center at The University of Alabama at Birmingham (UAB) (Press release, Clovis Oncology, JUN 23, 2021, View Source [SID1234584262]).

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The O’Neal Comprehensive Cancer Center at UAB is among the nation’s leading cancer research institutions and one of only 51 comprehensive cancer centers designated by the National Cancer Institute.

The Phase 1 portion of the LuMIERE study will evaluate the safety of the FAP-targeting investigational therapeutic agent and identify the recommended Phase 2 dose and schedule of lutetium-177 labeled FAP-2286 (177Lu-FAP-2286). FAP-2286 labeled with gallium-68 (68Ga-FAP-2286) will be utilized as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment with the therapeutic agent. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types.

"I envision that targeted radionuclide therapy has the potential to transform how we diagnose and treat cancer and I look forward to exploring this in the LuMIERE clinical trial," said Thomas Hope, M.D., Director of Molecular Therapy in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco and lead investigator of the LuMIERE trial.

"We are pleased to initiate sponsored clinical development of FAP-2286 with the LuMIERE study based on the clinical community’s enthusiasm to further explore the potential of targeted radionuclide therapy and FAP as a therapeutic target," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "Given FAP is highly expressed in many of the hardest-to-treat solid tumors, we look forward to exploring the potential of FAP-2286 to treat patients with cancer as our first entry into this emerging field of targeted radiotherapy. The O’Neal Comprehensive Cancer Center and each of the clinical trial sites expected to open for enrollment in the near future bring tremendous nuclear medicine and medical oncology expertise as well as passion for the program."

FAP is a cell-surface protein that is expressed in limited amounts by normal tissues, but highly expressed in cancer-associated fibroblasts (CAFs) present in the tumor microenvironment of many solid tumors including breast, lung, colorectal and pancreatic carcinomas.i,ii,iii,iv Preclinical data demonstrate that 177Lu-FAP-2286 potently and selectively binds FAP on the surface of CAFs and tumor cells to deliver the beta particle-emitting radioisotope 177Lu, resulting in DNA damage and cell death.v Compelling anti-tumor efficacy of 177Lu-FAP-2286 has been demonstrated in FAP-expressing preclinical tumor models.vi

To learn more about targeted radiotherapy, FAP-2286 and Clovis’ targeted radionuclide development program, visit www.targetedradiotherapy.com.

About FAP-2286

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use. FAP is highly expressed in many epithelial cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas.Clovis holds U.S. and global rights for FAP-2286 excluding Europe, Russia, Turkey, and Israel.

FAP-2286 is an unlicensed medical product.

About Targeted Radionuclide Therapy

Targeted radionuclide therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing delivery of radiation to normal tissue. Targeted radionuclides are created by linking radioactive isotopes, also known as radionuclides, to targeting molecules (e.g., peptides, antibodies, small molecules) that can bind specifically to tumor cells or other cells in the tumor environment. Based on the radioactive isotope selected, the resulting agent can be used to image and/or treat certain types of cancer. Agents that can be adapted for both therapeutic and imaging use are known as "theranostics." Clovis is developing a pipeline of novel, targeted radiotherapies for cancer treatment and imaging, including its lead candidate, FAP-2286, an investigational peptide-targeted radionuclide therapeutic (PTRT) and imaging agent, as well as three additional discovery-stage compounds.

On June 23, 2021 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a global biotechnology company focused on developing and commercializing innovative medicines worldwide, reported that the China National Medical Products Administration (NMPA) has granted its anti-PD-1 antibody tislelizumab approval for the first-line treatment of patients with advanced non-squamous non-small cell lung cancer (NSCLC) and conditional approval for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with at least one systemic therapy (Press release, BeiGene, JUN 23, 2021, View Source [SID1234584261]).

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"With today’s approvals, tislelizumab is now available in China in five indications covering lung, liver, bladder, and lymphoma, and is becoming an important immunotherapy in the world’s most populous country," commented Xiaobin Wu, Ph.D., President, Chief Operating Officer, and General Manager of China at BeiGene. "This remarkable achievement, which began approximately 18 months ago with tislelizumab’s initial approval, was made possible through BeiGene’s integrated global clinical development approach. We hope to make tislelizumab available broadly in China through our science-based commercial team and globally through our collaboration with Novartis, in furtherance of our goal of expanding access to innovative, quality cancer treatments for more people worldwide."

"We are pleased about the concurrent approvals for tislelizumab in China – in first-line non-squamous NSCLC following the previous approval for NSCLC patients with squamous histology earlier this year, and in second- or third-line HCC, which was based on the results from the largest global single-arm pivotal trial of any anti-PD-1 antibody in this indication," said Yong (Ben) Ben, M.D., Chief Medical Officer, Immuno-Oncology at BeiGene. "The pivotal clinical program of tislelizumab has seen tremendous progress lately, including two positive Phase 3 trials, one in esophageal cancer and the other in nasopharyngeal cancer. We credit our accomplishment to the dedication of our BeiGene team, and most importantly, the trust from participating patients and their loved ones, as well as investigators leading these clinical trials."

NMPA Approval in First-Line Advanced Non-Squamous NSCLC

"NSCLC comprises the most common form of lung cancer, although diagnoses are usually delayed with most patients diagnosed at advanced stage. In the Phase 3 RATIONALE 304 trial, tislelizumab in combination with pemetrexed and platinum chemotherapy demonstrated a clinically significant improvement in progression-free survival along with a high response rate, and was generally well-tolerated for treatment-naïve patients with advanced non-squamous NSCLC," commented Shun Lu, M.D., Ph.D., Professor of Shanghai Chest Hospital at Jiao Tong University and lead investigator for the trial. "I believe that this approval could help meet the significant demand in the front-line care of NSCLC, and I also look forward to the overall survival data readout."

The approval of tislelizumab for the first-line treatment of patients with advanced non-squamous NSCLC was supported by clinical results from a Phase 3 trial (NCT03663205) of tislelizumab in combination with pemetrexed and platinum chemotherapy (either carboplatin or cisplatin) in patients with stage IIIB or stage IV non-squamous NSCLC, compared to pemetrexed and platinum alone. A total of 334 patients in China were enrolled in the trial, randomized 2:1 to either the tislelizumab and chemotherapy arm or the chemotherapy arm. As announced in April 2020, the trial met the primary endpoint of statistically significant improvement in progression-free survival (PFS), as assessed by independent review committee (IRC), in the pre-planned interim analysis. The safety profile of tislelizumab in combination with chemotherapy was consistent with the known risks of each study treatment, and no new safety signals were identified. The results of the interim analysis of the trial were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 in September 2020.

NMPA Approval in Second- or Third-Line HCC

The NMPA conditional approval of tislelizumab in patients with HCC who have received at least one systemic therapy is based on clinical results from a single-arm, open-label, multicenter, global pivotal Phase 2 trial (NCT03419897) conducted in 249 patients from eight countries and regions in Asia and Europe, including 138 patients (55.4%) who received one line of prior systemic therapy and 111 patients (44.6%) who received at least two lines of prior therapies. Of all the patients enrolled in the trial, the median age was 62 years and 63.9% of patients had history of viral hepatitis, with hepatitis B accounting for the majority (51.4%) followed by hepatitis C (14.5%).

"Hepatocellular carcinoma is a difficult-to-treat primary liver cancer, most commonly found in those living with chronic liver diseases, such as hepatitis B and C. Based on the encouraging efficacy and safety results in patients with advanced liver cancer from this trial, tislelizumab has the potential to bring long-term survival benefits to patients with second- or third-line HCC in China," commented Zhenggang Ren, M.D., Ph.D., Professor at Zhongshan Hospital, Fudan University, and the trial’s leading investigator in China.

With a median follow-up time of 12.4 months, objective response rate (ORR) as assessed by IRC per RECIST v1.1 was 13.3% (95% CI: 9.3, 18.1), including three complete responses (CRs); disease control rate (DCR) was 53.0% (95% CI: 46.6, 59.3); among patients who achieved a CR or partial response (PR), 90.4% (95% CI: 73.1, 96.8) and 79.2% (95% CI: 59.3, 90.2) of them sustained response at six months and 12 months, respectively. Median overall survival (OS) was 13.2 months (95% CI: 10.8, 15.0) and PFS was 2.7 months (95% CI: 1.4, 2.8).

The safety profile of tislelizumab as a monotherapy in the label in China was based on 1,183 patients who received tislelizumab as a monotherapy in five clinical trials, including the pivotal Phase 2 trial in HCC. The most common adverse reactions (≥10%) were aspartate aminotransferase (AST) increased, alanine aminotransferase (ALT) increased, rash, and fatigue. Grade ≥3 adverse reactions occurred in 17.3% of patients, with the most common (≥1%) being AST increased, ALT increased, gamma-glutamyltransferase increased, anemia, pneumonitis, and lung infection. For tislelizumab as a monotherapy, the most common immune-mediated adverse reactions were immune-mediated pneumonitis, diarrhea and colitis, hepatitis, nephritis, endocrinopathies (hypothyroidism, hyperthyroidism, thyroiditis, adrenocortical insufficiency, and hyperglycemia and Type 1 diabetes mellitus), skin adverse reactions, pancreatitis, myocarditis, and myositis.

About Non-Small Cell Lung Cancer

Lung cancer is the second most common type of cancer and the leading cause of cancer-related death worldwide.i NSCLC accounts for approximately 85% of all lung cancer cases and is usually diagnosed at an advanced stage.ii For patients with advanced NSCLC that has metastasized to distant regions or organs in the body, the relative five-year survival rate is approximately 6%.iii In 2020, there were an estimate of 815,563 new cases of lung cancer in China, accounting for 37% of all incidences worldwide.iv

About Hepatocellular Carcinoma

HCC is a major global health problem, accounting for 85-90 percent of all reported cases of liver cancer.v Liver cancer is the sixth most common type of cancer, with an estimated 905,677 new cases in 2020 worldwide; it was also the third most common cause of cancer-related mortality, responsible for an estimated 830,180 deaths in 2020.i China accounts for approximately 50 percent of both new HCC cases and HCC-related deaths worldwide in 2020.iv

About Tislelizumab

Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

The China National Medical Products Administration (NMPA) has granted tislelizumab in five indications, including full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy and for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy; and conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies, for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy, and for the treatment of patients with hepatocellular carcinoma (HCC) who have received at least one systemic therapy. Full approval for these indications is contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

In addition, two supplemental Biologics License Applications for tislelizumab have been accepted by the Center for Drug Evaluation (CDE) of the NMPA and are under review for second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy and for patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors.

BeiGene has initiated or completed 17 potentially registration-enabling clinical trials in China and globally, including 13 Phase 3 trials and four pivotal Phase 2 trials.

In January 2021, BeiGene and Novartis entered into a collaboration and license agreement granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

Tislelizumab is not approved for use outside of China.

About the Tislelizumab Clinical Program

Clinical trials of tislelizumab include:

Phase 3 trial comparing tislelizumab with docetaxel in the second- or third-line setting in patients with NSCLC (NCT03358875);
Phase 3 trial comparing tislelizumab to salvage chemotherapy in patients with relapsed or refractory classical Hodgkin Lymphoma (cHL; NCT04486391);
Phase 3 trial in patients with locally advanced or metastatic urothelial carcinoma (NCT03967977);
Phase 3 trial of tislelizumab in combination with chemotherapy versus chemotherapy as first-line treatment for patients with advanced squamous NSCLC (NCT03594747);
Phase 3 trial of tislelizumab in combination with chemotherapy versus chemotherapy as first-line treatment for patients with advanced non-squamous NSCLC (NCT03663205);
Phase 3 trial of tislelizumab in combination with platinum-based doublet chemotherapy as neoadjuvant treatment for patients with NSCLC (NCT04379635);
Phase 3 trial of tislelizumab combined with platinum and etoposide versus placebo combined with platinum and etoposide in patients with extensive-stage small cell lung cancer (NCT04005716);
Phase 3 trial comparing tislelizumab with sorafenib as first-line treatment for patients with hepatocellular carcinoma (HCC; NCT03412773);
Phase 2 trial in patients with previously treated unresectable HCC (NCT03419897);
Phase 2 trial in patients with locally advanced or metastatic urothelial bladder cancer (NCT04004221);
Phase 3 trial comparing tislelizumab with chemotherapy as second-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC; NCT03430843);
Phase 3 trial of tislelizumab in combination with chemotherapy as first-line treatment for patients with ESCC (NCT03783442);
Phase 3 trial of tislelizumab versus placebo in combination with chemoradiotherapy in patients with localized ESCC (NCT03957590);
Phase 3 trial of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment for patients with gastric cancer (NCT03777657);
Phase 2 trial of tislelizumab in patients with relapsed or refractory cHL (NCT03209973);
Phase 2 trial in patients with MSI-H/dMMR solid tumors (NCT03736889); and
Phase 3 trial of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment in patients with nasopharyngeal cancer (NCT03924986).
BeiGene Oncology

BeiGene is committed to advancing best and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines to patients across the globe. We have a growing R&D team of approximately 2,300 colleagues dedicated to advancing more than 90 clinical trials involving more than 13,000 patients and healthy volunteers. Our expansive portfolio is directed by a predominantly internalized clinical development team supporting trials in more than 40 countries. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. The Company currently markets three medicines discovered and developed in our labs: BTK inhibitor BRUKINSA in the United States, China, Canada, and additional international markets; and non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab and PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.