On December 10, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the phase II coopERA Breast Cancer study met its primary endpoint in the neoadjuvant treatment of early stage ER-positive, HER2-negative breast cancer (Press release, Hoffmann-La Roche, DEC 10, 2021, View Source [SID1234596754]). Breast cancer is the most frequently diagnosed type of cancer, with major societal impact.2 Hormone receptor (HR)-positive breast cancer is the most common subtype, representing ~70% of all diagnoses, or an estimated 1.6 million cases annually across the world.2,3

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"The coopERA Breast Cancer results show the potential positive impact giredestrant could bring for people with early, oestrogen receptor-positive breast cancer, and provide a strong rationale for our ongoing phase III lidERA Breast Cancer study in the adjuvant setting," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "At Roche, we are striving to develop new treatments that might improve or extend the lives of many people with ER-positive breast cancer."

The coopERA Breast Cancer trial is evaluating the efficacy and safety of neoadjuvant treatment with giredestrant (formerly known as GDC-9545), an investigational next generation selective oestrogen receptor degrader (SERD) versus standard of care treatment (anastrozole) in postmenopausal women with oestrogen receptor (ER)-positive, HER2-negative, untreated early breast cancer. The primary endpoint of the study, which measured suppression of the tumour proliferation marker Ki67 was met, following two weeks of treatment with giredestrant versus anastrozole:1

Giredestrant showed a statistically significant mean Ki67 reduction of 75% (95% CI: –80%, –70%) versus 67% for anastrozole (95% CI: –73%, –59%; p=0.0433).
The secondary endpoint of complete cell cycle arrest rate was 19.6% with giredestrant versus 12.8% with anastrozole (95% CI: -4.25, 17.97), which suggests that giredestrant was better at stopping tumour cell proliferation than anastrozole.
Giredestrant was found to be well tolerated and have a safety profile consistent with previous clinical trials.4,5
Final analysis, including overall response rates and combination data with palbociclib are expected next year.
"A significant unmet need remains in early ER-positive breast cancer with currently around half of people having to stop treatment for reasons such as the toll of side effects," said Sara Hurvitz, coopERA Breast Cancer Principal Investigator. "The superior, robust anti-tumour activity of giredestrant after just two weeks of treatment in coopERA Breast Cancer provides early insights into its potential as an effective and tolerable alternative treatment in the early-stage setting."

The coopERA Breast Cancer study is one of several studies to be presented at the San Antonio Breast Cancer Symposium (7-10 December 2021) showing progress in Roche’s comprehensive ER-positive clinical development programme and it provides further evidence of giredestrant’s clinical activity and tolerable safety profile. This includes:

Abstract #1842 – an analysis of the GO39932 study demonstrated encouraging clinical activity of giredestrant as a single agent and in combination with palbociclib, with consistent activity across analysed biomarkers.6
Abstract #1186 – a comprehensive cardiac safety analysis of the GO39932 study found no clinically relevant cardiac effects with 100 mg of giredestrant. A lower, standardised once-daily 30 mg dose has been selected for the giredestrant development programme.7
Abstract #2041 – a ‘trial in progress’ update on the phase III lidERA Breast Cancer study, investigating giredestrant in over 4,000 people with early-stage ER-positive, HER2-negative breast cancer. It is the first study to evaluate an oral SERD in the adjuvant setting.8

About giredestrant
Giredestrant is a potent, next generation investigational selective oestrogen receptor (SERD) with best-in-class potential. It is designed to fully block oestrogen receptor (ER) signalling with robust receptor occupancy and demonstrates an exceptional preclinical profile. Oestrogen encourages ER-positive breast cancer cells to grow by attaching to the ER. Giredestrant works by blocking this receptor to prevent the action of oestrogen, and in the process causes the receptor to be degraded. This investigational medicine has also shown efficacy regardless of ESR1 mutation status (mutations in the ESR1 gene are important mechanisms of resistance to hormone therapy).9,10,11,12,13

Given orally, giredestrant delivers an encouraging clinical efficacy and safety profile and has shown superior pre-clinical potency over other SERDs in development. The oral administration of giredestrant has the potential to transform the treatment experience for patients, offering greater convenience and a less painful option compared to therapies administered via intramuscular injection.4,5,9

Giredestrant has a comprehensive development programme across a broad range of settings and treatment combinations for patients with ER-positive, HER2-negative breast cancer. Roche have completed recruitment of patients into a phase II study in second/third-line ER-positive, HER2-negative locally advanced or metastatic breast cancer (acelERA Breast Cancer), and are currently enrolling patients into two phase III studies (persevERA Breast Cancer, lidERA Breast Cancer) evaluating giredestrant across early and metastatic ER-positive, HER2-negative breast cancer settings, as a monotherapy or in combination with palbociclib. In the phase I/II MORPHEUS study giredestrant is being investigated in combination with multiple treatment partners in pre-treated metastatic ER-positive, HER2-negative breast cancer. We are also planning to investigate giredestrant in ER-positive, HER2-positive breast cancer. A standardised once-daily 30 mg dose has been selected for the giredestrant development programme.14,15,16,17

Giredestrant received U.S. Food and Drug Administration Fast Track Designation (FTD) as a second and third-line treatment for ER-positive, HER2-negative, metastatic breast cancer. FTD is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.18

About coopERA Breast Cancer (NCT04436744)19
An open-label, two-arm, phase II study to evaluate the efficacy, safety, and pharmacokinetics of giredestrant versus anastrozole (in the window of opportunity phase) and giredestrant plus palbociclib compared with anastrozole plus palbociclib (in the neoadjuvant phase) in postmenopausal women with untreated, ER-positive, HER2-negative early breast cancer. The primary endpoint of the study is the geometric change in Ki67 scores (a measure of how quickly cancer cells are proliferating) from baseline to week 2 during the window of opportunity phase. Secondary endpoints include complete cell cycle arrest rate, safety outcomes and plasma concentration of giredestrant.

About lidERA Breast Cancer20
An open-label, two-arm, randomised, multicentre, phase III study to evaluate efficacy and safety of adjuvant giredestrant compared with endocrine therapy of physician’s choice in people with medium- and high-risk stage I-III ER-positive, HER2-negative early breast cancer. The primary endpoint of the study is invasive disease-free survival (iDFS), measured from randomisation to the first occurrence of an iDFS event (up to 10 years). Secondary endpoints include overall survival and disease-free survival. LidERA Breast Cancer is currently the only ongoing early breast cancer trial investigating an oral SERD.

About Roche in breast cancer
Roche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough innovations in HER2-positive and triple-negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for all forms of early and advanced breast cancer, including triple-negative and hormone receptor-positive.

Our targeted medicines Herceptin (trastuzumab), Perjeta (pertuzumab), Phesgo, Kadcyla (trastuzumab emtansine) and Tecentriq (atezolizumab) are continuing to transform the treatment of early and advanced HER2-positive and triple-negative breast cancers and, through our clinical programmes, we hope to bring new treatment combinations to people with breast cancer, ultimately improving outcomes.

On December 10, 2021 BeiGene (NASDAQ: BGNE; HKEX: 06160), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, reported results from the RATIONALE 309 trial of tislelizumab versus placebo in combination with chemotherapy as a first-line treatment for patients with recurrent or metastatic nasopharyngeal cancer (RM-NPC) at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress 2021, taking place on December 8-11, 2021 (Press release, BeiGene, DEC 10, 2021, View Source [SID1234596776]).

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"We are pleased that tislelizumab in combination with chemotherapy demonstrated a statistically significant progression-free survival benefit for patients with RM-NPC over chemotherapy," commented Yong (Ben) Ben, M.D., Chief Medical Officer, Immuno-Oncology at BeiGene. "A filing based on these results is currently under review in China, where NPC as an endemic disease remains a significant unmet medical need. We look forward to continued discussions with the health authority and are working to bring this important immunotherapy to patients in China as soon as we can."

In August 2021, the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) accepted a supplement Biologics License Application (sBLA) for tislelizumab in combination with chemotherapy as a first-line treatment for patients with RM-NPC based on results from the interim analysis of the RATIONALE 309 trial.

Results from RATIONALE 309: Tislelizumab vs. Placebo in Combination with Chemotherapy in First-Line RM-NPC

Proffered Paper: 121O

RATIONALE 309 is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial (NCT03924986) designed to evaluate the efficacy and safety of tislelizumab combined with gemcitabine and cisplatin (Arm A) versus placebo combined with gemcitabine and cisplatin (Arm B) as a first-line treatment for patients with RM-NPC. The primary endpoint of the trial is progression-free survival (PFS) in the intent-to-treat (ITT) population as assessed by an independent review committee (IRC) per RECIST v1.1 criteria; secondary endpoints include IRC-assessed overall response rate (ORR), IRC-assessed duration of response (DoR), overall survival (OS), investigator-assessed PFS, time to second objective disease progression (PFS2), and safety. A total of 263 patients were enrolled in the trial, with 131 and 132 randomized to Arm A and Arm B, respectively, with balanced baseline characteristics between both arms.

"In the RATIONALE 309 trial, the addition of tislelizumab to chemotherapy significantly prolonged PFS for previously untreated patients with RM-NPC, an aggressive head and neck cancer prevalent in Asia, with consistent survival benefit across patient subgroups. Safety results in both arms remained similar to known risks and no new safety signals were identified. The promising results support the potential of tislelizumab in combination with chemotherapy as a new standard of care in China for the first-line treatment of RM-NPC," commented Yunpeng Yang, M.D., Professor at Sun Yat-sen University Cancer Center and principal investigator of the study.

As of March 26, 2021, with a median follow-up time of 10.0 months, RATIONALE 309 achieved the primary endpoint at the interim analysis, with the combination of tislelizumab and chemotherapy demonstrating a statistically significant improvement in PFS, compared to the combination of placebo and chemotherapy, per IRC assessment. Efficacy results included:

The median PFS was 9.2 months (95% CI: 7.6, 10.1) in Arm A, compared to 7.4 months (95% CI: 5.6, 7.5) in Arm B, with a stratified hazard ratio (HR) of 0.52 (95% CI: 0.38, 0.73) and stratified log-rank p < 0.0001, as assessed by IRC;
The PFS rate at six, nine, and 12 months was 66.1% (95% CI 56.9, 73.8), 51.0% (95% CI: 41.1, 60.1), and 35.7% (95% CI: 25.2, 46.4) in Arm A, compared to 53.0% (95% CI: 43.4, 61.8), 21.6% (95% CI: 13.5, 30.9), and 12.2% (95% CI: 5.6, 21.4) in Arm B, as assessed by IRC;
The median PFS was 9.8 months (95% CI: 7.8, 11.9) in Arm A, compared to 7.6 months (95% CI: 6.6, 7.8) in Arm B, with a stratified HR of 0.54 (95% CI: 0.38, 0.76), as assessed by investigators;
Consistent PFS benefit was observed in most subgroups, including disease status, baseline liver metastases, and gender;
The ORR and complete response (CR) rate were 69.5% and 16.0% in Arm A, compared to 55.3% and 6.8% in Arm B, as assessed by IRC; and
The median DoR was 8.5 months (95% CI: 6.5, NE), compared to 6.1 months (95% CI: 4.7, 6.2) as assessed by IRC.
The safety profile of tislelizumab and chemotherapy combination was manageable, consistent with known risks of each treatment agent. Safety results included:

All patients (100%) in Arm A experienced at least one treatment-emergent adverse event (TEAE) of any grade, with the most common (≥20.0%) being anemia, decreased white blood cell count, decreased neutrophil count, nausea, decreased platelet count, decreased appetite, vomiting, constipation, leukopenia, neutropenia, rash, hypothyroidism, increased alanine aminotransferase (ALT), hyponatremia, increased blood creatinine, increased aspartate aminotransferase (AST), malaise, and pyrexia;
In comparison, 131 patients (99.2%) in Arm B experienced at least one TEAE of any grade, with the most common (≥20.0%) being anemia, nausea, decreased white blood cell count, decreased platelet count, decreased neutrophil count, vomiting, decreased appetite, constipation, leukopenia, neutropenia, hyponatremia, malaise, hypokalemia, rash, increased AST, and hypoalbuminemia;
Grade ≥3 TEAEs were reported in 106 patients (80.9%) in Arm A, compared to 108 patients (81.8%) in Arm B;
Serious TEAEs were reported in 36 patients (27.5%) in Arm A, compared to 44 patients (33.3%) in Arm B;
TEAEs leading to permanent treatment discontinuation and death occurred in 2 patients (1.5%) and 5 patients (3.8%), respectively, in Arm A, compared to 3 patients (2.3%) and 2 patients (1.5%), respectively, in Arm B; and
In Arm A, 24 patients (18.3%) experienced at least one immune-mediated TEAE of any grade, including 3 patients (2.3%) reporting Grade ≥3 events.
About Nasopharyngeal Cancer

Nasopharyngeal cancer (NPC) is a malignant, squamous cell carcinoma which arises from the epithelial cells of the nasopharynx, most commonly originating in the pharyngeal recess (the fossa of Rosenmüller).1 There were an estimated 62,555 new cases of NPC in China in 2020, accounting for 46.8 percent of the worldwide incidence.2 Despite the heavy public health burden of NPC in southern China and other endemic areas, relatively little is known about the etiology and prevention of NPC.3 The major risk factors for NPC are genetic predisposition, Epstein-Barr virus (EBV) infection, and consumption of salt-preserved food.4 The median overall survival rate is about 20 months in advanced NPC;5 however, progressively worsening prognoses falling to a three-year survival of 7-40% were reported in patients with recurrent or metastatic NPC, indicating a high medical unmet need for more effective treatment.6,7,8

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 approved 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. NMPA also granted 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, four supplemental Biologics License Applications for tislelizumab are under review by the Center for Drug Evaluation (CDE) of the NMPA, including as second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy, for patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors, for the treatment of patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have disease progression following or are intolerant to first-line standard chemotherapy, and for first-line treatment of patients with recurrent or metastatic nasopharyngeal cancer (NPC).

In the U.S., a Biologics License Application for tislelizumab as a treatment for patients with unresectable recurrent locally advanced or metastatic ESCC after prior systemic therapy is currently under review by the U.S. Food and Drug Administration with a PDUFA target action date of July 12, 2022.

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 2,750 colleagues dedicated to advancing more than 70 ongoing clinical trials involving more than 14,000 patients and healthy volunteers. Our expansive portfolio is directed by a predominantly internalized clinical development team supporting trials in more than 45 countries and regions. 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, Bristol Myers Squibb, and EUSA Pharma. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, 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.

On December 10, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported new follow-up efficacy, safety and patient-reported outcomes (PROs) data from the phase II CITYSCAPE trial, investigating the novel anti-TIGIT cancer immunotherapy tiragolumab plus Tecentriq (atezolizumab) compared with Tecentriq alone as an initial (first-line) treatment for people with PD-L1-positive metastatic non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, DEC 10, 2021, View Source [SID1234596738]). The full results are being featured as an oral presentation in the Proffered Paper session 2 (Abstract LBA2) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress 2021, taking place 8-11 December.1

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"These encouraging results suggest that combining anti-TIGIT and anti-PD-L1 cancer immunotherapies such as tiragolumab and Tecentriq could potentially represent a novel approach to address unmet needs in cancer," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "With tiragolumab, we have the largest and most advanced anti-TIGIT clinical programme, and we look forward to the results of our phase III trials in lung cancer and other challenging tumour types."

After 2.5 years median follow-up, tiragolumab plus Tecentriq continued to show an improvement in the intention-to-treat (ITT) population (n=67), driven by the PD-L1-high population (TPS ≥ 50%) (n=29). In the ITT population, the combination reduced the risk of disease worsening or death (progression-free survival; PFS) by 38% (median PFS=5.6 vs. 3.9 months; hazard ratio (HR)=0.62, 95% CI: 0.42-0.91) and improved overall response rates (ORR) (38.8% vs. 20.6%) compared with Tecentriq alone. A predefined exploratory analysis in the PD-L1-high population showed a 71% reduction in the risk of disease worsening or death (median PFS=16.6 vs. 4.1 months; HR=0.29, 95% CI: 0.15-0.53) and a clinically meaningful improvement in ORR (69% vs. 24.1%) with the combination compared with Tecentriq alone.1

The analysis also showed that tiragolumab plus Tecentriq improved overall survival (OS), a secondary endpoint of the study, in the ITT population, which was driven by the PD-L1-high population. After 2.5 years median follow-up, median OS was 23.2 vs. 14.5 months (HR=0.69, 95% CI: 0.44-1.07) in the ITT population. The exploratory data in the PD-L1-high population showed a clinically meaningful OS improvement. The median was not reached for the tiragolumab regimen and is projected to be greater than 30.3 months based on the lower confidence interval (NE (30.3-NE) vs. 12.8 months (4.7-24.2); HR=0.23, 95% CI: 0.10-0.53).1

Data suggest that the combination was generally well-tolerated, showing similar rates of Grade 3-4 treatment-related adverse events (AEs) when adding tiragolumab to Tecentriq compared with Tecentriq alone (22.4% vs. 25%). The most common all cause AEs (rate greater than 5% difference between study groups) seen with the combination were infusion-related reactions, stiffness, dry skin, fatigue and rash. After longer follow-up, no new safety signals were observed with the combination. Patients generally reported minimal-to-moderate symptoms and generally maintained their quality of life compared with the start of treatment. PRO data from this exploratory analysis showed that lung symptoms, such as dyspnoea and pain, did not appear to deteriorate with the addition of tiragolumab to Tecentriq.1

CITYSCAPE study forms the basis of an industry-leading development programme across multiple settings and tumour types.3

The phase III SKYSCRAPER-01 trial is currently ongoing to confirm these results in the PD-L1-high population, with the goal of bringing this treatment option to patients. Earlier this year, tiragolumab was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration – representing the first anti-TIGIT therapy to be granted this designation and the 37th BTD for Roche’s portfolio of medicines. Since 2020, Roche has initiated five phase III trials evaluating tiragolumab plus Tecentriq in early and metastatic disease in lung (SKYSCRAPER-01, SKYSCRAPER-02, SKYSCRAPER-03) and oesophageal cancers (SKYSCRAPER-07, SKYSCRAPER-08). Tiragolumab is also being evaluated in other solid tumours as well as in haematological cancers.

About the CITYSCAPE study1
CITYSCAPE is a global phase II, randomised and blinded study evaluating tiragolumab plus Tecentriq (atezolizumab) compared with Tecentriq alone in 135 patients with first-line PD-L1-positive locally advanced, unresectable or metastatic non-small cell lung cancer. Patients were randomised 1:1 to receive either tiragolumab plus Tecentriq or placebo plus Tecentriq, until progressive disease or loss of clinical benefit. Co-primary endpoints are overall response rate (ORR) and progression-free survival (PFS). Secondary endpoints include safety, overall survival (OS) and patient-reported outcomes (PROs). PRO results were assessed with EORTC QLQ-C30, a questionnaire developed to assess the quality of life of people with cancer, administered at baseline and throughout study treatment.

About tiragolumab
Tiragolumab is a first-in-class novel immune checkpoint inhibitor with an intact Fc region. Tiragolumab selectively binds to TIGIT, a novel inhibitory immune checkpoint which suppresses the immune response to cancer.1 Based on preclinical research, tiragolumab is thought to work as an immune amplifier with other cancer immunotherapies such as Tecentriq.2 The TIGIT pathway is distinct but complementary to the PD-L1/PD-1 pathway. Dual blockade with tiragolumab and Tecentriq may help overcome immune suppression and restore the immune response.1

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called Programmed Death Ligand-1 (PD-L1), which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of NSCLC, SCLC, certain types of metastatic urothelial cancer, in PD-L1-positive metastatic triple-negative breast cancer and for hepatocellular carcinoma. In the US, Tecentriq is also approved in combination with Cotellic (cobimetinib) and Zelboraf (vemurafenib) for the treatment of people with BRAF V600 mutation-positive advanced melanoma.

About Roche in cancer immunotherapy
Roche’s rigorous pursuit of groundbreaking science has contributed to major therapeutic and diagnostic advances in oncology over the last 50 years, and today, realising the full potential of cancer immunotherapy is a major area of focus. With over 20 molecules in development, Roche is investigating the potential benefits of immunotherapy alone, and in combination with chemotherapy, targeted therapies or other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system to attack their cancer. Our scientific expertise, coupled with innovative pipeline and extensive partnerships, gives us the confidence to continue pursuing the vision of finding a cure for cancer by ensuring the right treatment for the right patient at the right time.

In addition to Roche’s approved PD-L1 checkpoint inhibitor, Tecentriq (atezolizumab), Roche’s broad cancer immunotherapy pipeline includes other checkpoint inhibitors, such as tiragolumab, a novel cancer immunotherapy designed to bind to TIGIT, individualised neoantigen therapies and T-cell bispecific antibodies.

On December 10, 2021 Inceptua Group – pharmaceutical company and service partner – reported that the European Commission (EC) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) has approved the transfer of the marketing authorization for Apealea (paclitaxel micellar) from Oasmia Pharmaceutical AB to Inceptua AB (Press release, Inceptua Medicines, DEC 10, 2021, View Source;utm_medium=rss&utm_campaign=inceptua-receives-approval-of-marketing-authorization-transfer-of-apealea-paclitaxel-micellar-for-the-treatment-of-ovarian-cancer [SID1234596756]). Apealea is approved in combination with carboplatin for the treatment of adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer.

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Inceptua have the exclusive right to distribute and commercialize Apealea in the EU, Norway, Iceland, Liechtenstein, Switzerland and the UK.

Stefan Fraenkel, Chief Executive Officer, Inceptua Group, says:

"We are pleased that the European Commission and MHRA has granted approval for Inceptua to market Apealea, Europe’s first non-Cremophor EL formulation of paclitaxel. With our deep commercialization capabilities and expertise, Inceptua is uniquely positioned to maximize the availability of Apealea for patients with ovarian cancer in this region."

Clive Whitcher, Head of Inceptua Pharma, says:

"With Apealea, ovarian cancer patients now have a treatment option that provides a shorter infusion time without mandatory premedication. We believe there is great potential for Apealea to help patients with ovarian cancer and we look forward to bringing this important treatment to patients in need throughout Europe."

On 25 March 2020, Oasmia Pharmaceutical AB and US based Elevar Therapeutics Inc. signed a global strategic partnership deal to commercialise Apealea. On 28 December 2020, Inceptua signed a licence agreement with Elevar Therapeutics Inc. to commercialise Apealea in Europe.

About Ovarian Cancer

Ovarian cancer is one of the most common female cancers affecting the primary reproductive organs.1 Globally, it is the third most common cancer among women and has the highest mortality rate2,3. Although ovarian cancer has a lower prevalence in comparison with breast cancer, it is three times more lethal, and it is predicted that, by the year 2040, the mortality rate of this cancer will rise significantly4,5. About half of the women who are diagnosed with ovarian cancer are 63 years or older and many of these patients are predisposed to age-related comorbidities, such as diabetes, which can influence treatment response and prognosis6.

About Apealea (paclitaxel micellar)

Apealea is a patented, water-soluble, intravenously injectable, non-Cremophor based formulation of paclitaxel that can be given without premedication such as steroids and with a shorter infusion time. Paclitaxel is a well-known chemotherapy agent used to treat breast, ovarian, lung, bladder, prostate, melanoma, and oesophageal cancer, as well as other types of solid tumour cancers. Cremophor-EL, is a formulation vehicle used for various poorly-water soluble drugs, including the anticancer agent paclitaxel and is associated with allergic reactions. Apealea received marketing authorization by the European Commission in November 2018, making it Europe’s first non-Cremophor-EL formulation of paclitaxel approved for use in ovarian cancer.

On December 10, 2021 The Multiple Myeloma Research Foundation (MMRF) reported that new insights related to novel targets, risk assessment, and precision medicine approaches generated through the use of the MMRF landmark CoMMpass Study will be presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Multiple Myeloma Research Foundation, DEC 10, 2021, View Source [SID1234596777]). In total, ASH (Free ASH Whitepaper) will feature 33 presentations developed through the work of more than 200 researchers from 180 institutions all using the CoMMpass data.

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The MMRF initiated the CoMMpass Study more than ten years ago to address the need for a large, comprehensive, genomic and clinical data set that was publicly available to researchers to realize the potential of precision medicine. It has now become one of the largest longitudinal genomic datasets of any cancer and the source of more than 150 myeloma scientific publications and abstracts. The insights generated by CoMMpass have led to groundbreaking discoveries that have transformed the research community’s understanding of myeloma at a genomic level. The MMRF is now working with five institutions (Beth Israel Deaconess Medical Center, Emory University, Mt. Sinai School of Medicine, Mayo Clinic, and Washington University, St. Louis) on a companion project called Immune Atlas that will complement the genomic and clinical data in CoMMpass with high dimensional immune profiling of the same patients, creating standards and generating robust immune data to further advance precision medicine. The initial findings from this effort are among the 33 abstracts.

"CoMMpass has exceeded our expectations as a wellspring for insightful research and to generate new hypotheses that we can test in the laboratory and at the bedside," said Hearn Jay Cho, MD, PhD, Chief Medical Officer, the MMRF. "CoMMpass continues to shape our research agenda, particularly in precision medicine clinical trials such as MyDRUG and MyCheckpoint, and this will only expand with the addition of Immune Atlas. We are also looking beyond CoMMpass by building our next major data set with the MMRF CureCloud."

The MMRF CureCloud was launched in 2019 as a next generation data source capturing genomic sequencing data through blood samples of newly diagnosed myeloma patients and longitudinal clinical data shared by patients through their electronic medical records. The first abstracts derived from CureCloud are being presented at ASH (Free ASH Whitepaper) representing the next game-changing longitudinal study in myeloma research. Unique to CureCloud is that it was specifically designed to not only power research, but also as an immediate and ongoing resource to clinicians and patients. Each CureCloud patient receives their personal genomic data report, learns about possible clinical trials, and will have ongoing access to new and evolving insights related to their disease. The database is designed to continuously identify insights from patients that will help other patients gain deeper understanding of possible treatment paths as more patients join the program.

"Our mission is to deliver a cure for each and every myeloma patient. We know that getting there will require access to data to progress the development of precision medicines. This is our ultimate focus as we share data with our research collaborators and patients every day," said Michael Andreini, President and CEO, the MMRF. "The data and insights we share are generating a deeper understanding of the biology of myeloma and helping to identify new targets and markers for risk and disease progression. They are also driving the discovery and delivery of more precise treatments for all patients as we pursue a world without myeloma."

For complete data on MMRF abstracts being presented at the 63rd ASH (Free ASH Whitepaper) Annual Meeting please contact C.J. Volpe at [email protected]

About the MMRF CoMMpass StudySM
The MMRF CoMMpass Study is a longitudinal study of patients with newly diagnosed active multiple myeloma. The goal is to map the genomic profile of each patient to clinical outcomes to develop a more complete understanding of patient responses to treatments. A cornerstone of the MMRF’s Personalized Medicine Initiative, the study is collecting and analyzing tissue samples, clinical data and genetic information from 1,000 newly diagnosed multiple myeloma patients for at least eight years. The CoMMpass Study was made possible by a $40M investment by the MMRF.
The MMRF CoMMpass Study opened in July of 2011 and now includes 1,150 patients from 76 sites in the United States, Canada and European Union. Data from the MMRF CoMMpass Study is made available to researchers via the MMRF’s Researcher Gateway (View Source), an online, open-access portal designed to make key genomic and clinical data available for additional study. The MMRF CoMMpass Study is being supported through a public-private partnership of patient donors and industry partners, including Takeda Oncology, Amgen, Bristol-Myers Squibb, Janssen Pharmaceuticals, Inc. and Janssen Diagnostics. Additional collaborating research partners include the Translational Genomics Research Institute, Van Andel Research Institute and GNS Healthcare. Please visit www.themmrf.org/research-partners/the-commpass-study to learn more about the study.