On July 21, 2017 Novartis reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of Rydapt (midostaurin) for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive (Press release, Novartis, JUL 21, 2017, View Source [SID1234519852]). If approved by the European Commission (EC), Rydapt will be indicated in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation chemotherapy, and for patients in complete response, followed by Rydapt single agent maintenance therapy, for adult patients with newly diagnosed AML who are FLT3 mutation-positive. Rydapt was also recommended for approval as monotherapy for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN) or mast cell leukemia.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

If approved, Rydapt will be the first targeted treatment available in the European Union (EU) for newly diagnosed FLT3 mutation-positive AML patients and advanced systemic mastocytosis (SM) patients. The opinion follows the recent US Food and Drug Administration (FDA) 2017 approval of Rydapt for FLT3-mutated AML and advanced SM on April 28 and the Swissmedic approval on May 4.

"Novartis is dedicated to bringing new treatment options to patients with rare diseases, including AML and advanced SM, which have seen limited treatment developments in the past 25 years," said Bruno Strigini, CEO, Novartis Oncology. "We are pleased with the positive recommendation from the CHMP and excited to move a step closer to bringing this much-needed treatment to these patients across Europe."

AML is a rare and aggressive cancer of the blood and bone marrow[2]. In the EU, there are over 18,000 estimated new cases of AML each year[3]. Approximately one-third of AML patients will have a FLT3 gene mutation[4].

FMS-like tyrosine kinase 3 (FLT3) is a type of cell-surface receptor which plays a role in increasing the number of certain blood cells[5] and the FLT3 gene mutation can result in faster disease progression, higher relapse rates and lower rates of survival than other forms of AML[4],[5],[6]. Prior to the approval of Rydapt in the US, the AML therapeutic strategy had remained relatively unchanged for more than 25 years[7],[8].

Advanced SM is a rare blood disorder characterized by uncontrolled growth and accumulation of mast cells – mediators of allergic responses – in one or more organs[9]. In advanced SM, mast cells accumulate in such high quantities that they begin to cause organ damage[9]. Median overall survival is currently less than six months for mast cell leukemia[10], two years for SM-AHN and 3.5 years for ASM[11].

The EC typically adheres to the recommendation of the CHMP and delivers its final decision within approximately two to three months. The decision will be applicable to all 28 EU member states, plus Iceland, Liechtenstein and Norway.

The positive opinion is based on the Phase III RATIFY (CALGB 10603 [Alliance]) clinical trial, which was conducted in collaboration with the Alliance for Clinical Trials in Oncology and 13 international cooperative groups. In the trial, newly diagnosed FLT3 mutation-positive patients who received Rydapt plus standard chemotherapy experienced significant improvement in overall survival with a 23% reduction in the risk of death compared with placebo plus standard chemotherapy, with median overall survival of 74.7 months and 25.6 months, respectively (hazard ratio [HR] = 0.77, 95% CI, 0.63, 0.95; one-sided p=0.0078)1. The full data from the RATIFY trial were recently published in the New England Journal of Medicine (NEJM)[12].

Event-free survival (EFS; event defined as no complete remission within 60 days of the start of induction therapy, relapse or death) was significantly longer for Rydapt plus chemotherapy versus placebo plus standard chemotherapy (median of 8.2 months compared to 3.0 months, HR = 0.78, 95% CI 0.66, 0.93 and one-sided p=0.0024). RATIFY is the largest worldwide clinical trial in newly diagnosed FLT3-mutated AML to date, as 3,277 AML patients were screened for the FLT3 mutation and 717 patients were enrolled[1].

In the Phase III AML RATIFY trial, the most frequent adverse reactions (incidence greater than or equal to 30%) in the Rydapt plus standard chemotherapy arm were febrile neutropenia, nausea, exfoliative dermatitis, vomiting, headache, petechiae (small red skin spots) and pyrexia. The most frequent non-hematologic Grade 3/4 adverse reaction was febrile neutropenia[1].

The recommendation in advanced SM is based on two single-arm open-label multicenter trials, including the Phase II study (CPKC412D2201), which was the largest prospective trial ever conducted in this rare disorder. The efficacy of Rydapt was established using modified Valent criteria, with patients demonstrating an overall response rate, defined as a major or partial response, of 59.6% (95% confidence interval [CI], 48.6, 69.8%). Efficacy was also assessed in a post-hoc analysis using the 2013 International Working Group-Myeloproliferative Neoplasms Research and Treatment-European Competence Network on Mastocytosis (IWG-MRT-ECNM) consensus criteria (n=113). This assessment estimated an overall response rate of 28.3% (95% CI, 20.2, 37.6)[1].

In advanced SM, the most frequent adverse reactions were nausea, vomiting, diarrhea, peripheral edema and fatigue. The most frequent Grade 3/4 adverse reactions were fatigue, sepsis, pneumonia, febrile neutropenia and diarrhea[1].

Rydapt Ongoing Clinical Development
In order to further investigate the potential of Rydapt in AML, Novartis is planning a Phase III study in newly diagnosed AML patients without a FLT3 mutation (wildtype).

About AML
AML is the most common acute leukemia in adults; it accounts for approximately 25% of all adult leukemias worldwide, with the highest incidence rates occurring in the US, Europe and Australia[13]. It also has the lowest survival rate of all adult leukemias[13].

AML prevents white blood cells from maturing, causing an accumulation of "blasts," which do not allow room for the normal blood cells[2]. Mutations in specific genes are found in many cases of AML[4], and genetic testing for mutations in newly diagnosed AML patients can help to determine prognosis and potential treatment strategies[14].

About Advanced SM
In advanced SM, the uncontrolled growth of neoplastic mast cells causes organ damage (e.g., liver dysfunction), low blood counts and weight loss[9]. Patients also suffer from debilitating systemic symptoms, such as pruritus (severe itching of the skin) caused by mast cells releasing inflammatory mediators, such as histamine, into the blood[9].

The uncontrolled proliferation of mast cells is caused in many people by a KIT gene mutation – the most common mutation, encoding the D817V substitution, occurs in approximately 90% of patients[15]. The KIT gene mutation results in activation of the KIT enzyme, which triggers the abnormal proliferation and survival of mast cells[16].

About Rydapt (midostaurin)
Rydapt (midostaurin) is an oral, multi-targeted inhibitor of multiple kinases, including FLT3 and KIT, which help regulate many essential cell processes, interrupting cancer cells’ ability to grow and multiply[17].

In the US, Rydapt is FDA-approved for the treatment of adults with newly diagnosed AML who are FMS-like tyrosine kinase 3 mutation-positive (FLT3+) as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy[17]. Rydapt is not indicated in the US as a single-agent induction therapy for the treatment of patients with AML. For a description of the experience with single-agent treatment beyond induction and consolidation, healthcare professionals in the US should refer to the Clinical Studies section of the US Prescribing Information (14.1)[17]. Rydapt is also approved to treat adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN) or mast cell leukemia, collectively referred to as advanced systemic mastocytosis (SM)[17].

The full US Prescribing Information for Rydapt can be found at: View Source

Rydapt is also approved in Switzerland, for use in combination with standard induction and consolidation chemotherapy, followed by maintenance monotherapy for treatment of newly diagnosed adult AML patients who have an FLT3 mutation. Rydapt is indicated in Switzerland for the treatment of adult patients with advanced SM.

Indications vary by country and not all indications are available in every country. The safety and efficacy profile of Rydapt has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that Rydapt will become commercially available for additional indications anywhere else in the world.

Rydapt Important Safety Information FROM THE US PRESCRIBING INFORMATION
Patients who are allergic to midostaurin or any of the ingredients in Rydapt should not take Rydapt. If a patient taking Rydapt develops signs of an allergic reaction, they should seek medical help immediately. Signs of an allergic reaction include trouble breathing, flushing, chest pain, throat tightness, and swelling of lips, mouth or throat.

Rydapt should be not be used during pregnancy since Rydapt may harm an unborn baby. Pregnancy testing should be conducted for women who might become pregnant. Effective birth control should be used during treatment and for at least four months after stopping Rydapt. If a patient becomes pregnant or thinks she may be, the patient should tell their doctor right away. Women should not breastfeed during treatment with Rydapt and for at least four months after the final dose. Men taking Rydapt who have female partners that are able to become pregnant should use effective birth control during his treatment with Rydapt and for at least four months after the last Rydapt dose. Rydapt may cause fertility problems in women and men, which may affect their ability to have children.

Rydapt may cause lung problems that may lead to death. Patients on Rydapt who develop a new or worsening cough, shortness of breath, or chest discomfort should get medical help right away. These may be signs of serious lung problems.

Common sides effects reported during Rydapt treatment for AML included low level of white blood cells with fever (febrile neutropenia); nausea; redness, pain or ulcers inside the mouth (mucositis); vomiting; headache; bruising; muscle or bone pain; nose bleeds; device-related infection; high blood sugar levels (hyperglycemia) and upper respiratory infections.

Common side effects reported during treatment for ASM, SM-AHM or mast cell leukemia included nausea; vomiting; diarrhea; swelling of the hands, feet or ankles; muscle or bone pain; stomach-area pain; tiredness; upper respiratory infection; constipation; fever; headache and trouble breathing.

If side effects including nausea, vomiting, and diarrhea occur, get worse or do not go away during treatment with Rydapt, patients should contact their doctor. Depending on the side effect and/or severity of the side effect that occur, their doctor may decrease their dose, temporarily stop, or completely stop treatment with Rydapt.

Patients should tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Rydapt may affect how these medicines work or these other medicines may affect how Rydapt works.

On July 21, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the EU Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Gazyvaro (obinutuzumab) in combination with chemotherapy, followed by Gazyvaro maintenance in people achieving a response, as a new treatment option for previously untreated advanced follicular lymphoma (Press release, Hoffmann-La Roche, JUL 21, 2017, View Source [SID1234519844]). The CHMP’s recommendation is based on results from the phase III GALLIUM study. Follicular lymphoma, the most common type of indolent (slow-growing) non-Hodgkin lymphoma, is considered incurable, and most people relapse repeatedly.1,2 Based on this positive CHMP recommendation, a final decision regarding the approval of Gazyvaro is expected from the European Commission in the near future.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"As follicular lymphoma is considered incurable, better initial treatment options are needed to prevent the disease from returning for as long as possible," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "MabThera has been the standard of care for the past 20 years. Based on the GALLIUM study, Gazyvaro-based therapy provides superior progression-free survival compared to MabThera-based therapy, setting a new benchmark for what can be achieved with initial therapy for follicular lymphoma."

The GALLIUM study is the first phase III study in previously untreated follicular lymphoma to show superior PFS over MabThera(rituximab)-based treatment, the current standard of care. Results showed that Gazyvaro-based treatment reduced the risk of disease progression or death (progression-free survival; PFS), as evaluated by investigator assessment, by 34 percent (HR=0.66; 95% CI 0.51-0.85, p=0.001) compared to MabThera-based treatment. As supported by an independent review committee (IRC), the risk of disease progression or death was reduced by 29 percent (HR=0.71; 95% CI 0.54-0.93, p=0.014) compared to MabThera/Rituxan-based treatment. Median PFS has not yet been reached in either treatment arm. Investigator assessment showed that at three years, 80.0 percent of patients who received Gazyvaro-based treatment were progression-free compared to 73.3 percent of patients who received MabThera-based treatment. Adverse events with either Gazyvaro or MabThera were consistent with those seen in previous studies.

About the GALLIUM study
GALLIUM (NCT01332968) is a global Phase III open-label, multi-centre, randomised two-arm study examining the efficacy and safety of Gazyvaro plus chemotherapy followed by Gazyvaro alone for up to two years, as compared head-to-head against MabThera plus chemotherapy followed by MabThera alone for up to two years or until disease progression (whichever occurs first). Chemotherapies (CHOP, CVP or bendamustine) were selected by each participating study site prior to beginning enrolment. GALLIUM included 1401 patients with previously untreated indolent non-Hodgkin lymphoma (iNHL), of which 1202 patients had follicular lymphoma. The primary endpoint of the study was investigator-assessed PFS in patients with follicular lymphoma, with secondary endpoints including PFS assessed by IRC, PFS in the overall study population (iNHL), response rate (overall response, ORR; and complete response, CR), overall survival (OS), and safety. The GALLIUM study is being conducted in cooperation with the NCRI (United Kingdom), GLSG (Germany), the East German Study Group Hematology and Oncology (OSHO; Germany).

About Gazyvaro (obinutuzumab)
Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system.

Gazyvaro is marketed as Gazyva outside the EU and Switzerland. Gazyva/Gazyvaro is currently approved in more than 80 countries in combination with chlorambucil, for people with previously untreated chronic lymphocytic leukaemia (CLL), and in combination with bendamustine for people with certain types of previously treated follicular lymphoma. The approvals in CLL were based on the CLL11 study, showing significant improvements with Gazyvaro plus chlorambucil across multiple clinical endpoints, including PFS, overall response rate (ORR), complete response rate (CR), and minimal residual disease (MRD) when compared head-to-head with MabThera plus chlorambucil.

The approvals in certain types of previously treated follicular lymphoma were based on the phase III GADOLIN study, in people with follicular lymphoma who did not respond to or who progressed during or within six months of prior MabThera -based therapy, showing a significant improvement in PFS and overall survival (OS) with Gazyvaro-based therapy compared to bendamustine alone.

Additional combination studies investigating Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are underway across a range of blood cancers.

About Follicular Lymphoma
Follicular lymphoma is the most common indolent (slow-growing) form of non-Hodgkin lymphoma (NHL), accounting for about one in five cases of NHL.1 It is considered incurable and relapse is common. Every day, more than 50 people in Europe are diagnosed with this type of NHL2. It is estimated that more than 75,000 people are diagnosed with follicular lymphoma each year worldwide2.

On July 21, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the EU Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for TECENTRIQ (atezolizumab) as a monotherapy for the treatment of adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) after they have been previously treated with chemotherapy (Press release, Hoffmann-La Roche, JUL 21, 2017, View Source [SID1234519843]). People with EGFR activating mutations or ALK positive tumour mutations should also have received targeted therapy before receiving TECENTRIQ. This positive recommendation is based on results from the large randomised Phase III OAK study and the randomised Phase II POPLAR study. The CHMP has also adopted a positive opinion for the use of TECENTRIQ as a monotherapy for the treatment of adults with locally advanced or metastatic urothelial carcinoma (mUC) who have been previously treated with a platinum based chemotherapy or who are considered ineligible for cisplatin chemotherapy. This positive opinion is based on results from the randomised Phase III IMvigor211 study and cohorts 1 and 2 from the single-arm Phase II IMvigor210 study.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This positive CHMP opinion represents great news for people living with either advanced lung or bladder cancer because, despite recent developments, long-term survival rates for people with these cancers are inferior to those with other common cancers," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are encouraged that the CHMP considered the totality of the data for TECENTRIQ including the importance of key clinical endpoints, such as long-term responses."
Based on this positive CHMP opinion, a final decision from the European Commisssion is expected in the near future. TECENTRIQ is already approved in the US and in a number of other countries for people with metastatic NSCLC; and for people with locally advanced or mUC and who are not eligible for cisplatin chemotherapy, or who have disease progression during or following platinum-containing therapy.
About the OAK study
OAK is a global, multicentre, open-label, randomised, controlled Phase III study that evaluated the efficacy and safety of TECENTRIQ compared with docetaxel. It enrolled 1225 patients with both squamous and non-squamous disease, regardless of the programmed death-ligand 1 (PD-L1) status of their tumours, and randomised them (1:1) to receive either TECENTRIQ administered intravenously at 1,200 mg every 3 weeks or docetaxel administered intravenously at 75 mg/m2 every 3 weeks. The co-primary endpoints were overall survival (OS) in the first 850 randomised patients (intention-to-treat population) and in a PD-L1-selected subgroup of this primary analysis population.
The OAK study showed that TECENTRIQ helped people in the overall study population live a median of 13.8 months – 4.2 months longer than those treated with docetaxel chemotherapy (median overall survival [OS]: 13.8 vs. 9.6 months; HR = 0.73, 95% CI: 0.62, 0.87).


CI=confidence interval; DOR=duration of response; IC=tumour-infiltrating immune cells; NE=not estimable; ORR=objective response rate; OS=overall survival; PFS=progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumours v1.1; *All comers refers to the primary analysis population consisting of the first 850 randomised patients ǂStratified by PD-L1 expression in tumour infiltrating immune cells, the number of prior chemotherapy regimens, and histology ** Based on the stratified log-rank test
About the POPLAR study
A phase II, multi-centre, international, randomised, open-label, controlled study, POPLAR, was conducted in patients with locally advanced or metastatic NSCLC who progressed during or following a platinum-containing regimen, regardless of PD-L1 expression. The primary efficacy outcome was overall survival. A total of 287 patients were randomised 1:1 to receive either TECENTRIQ (1,200 mg by intravenous infusion every 3 weeks until loss of clinical benefit) or docetaxel (75 mg/m2 by intravenous infusion on day 1 of each 3-week cycle until disease progression). Randomisation was stratified by PD-L1 expression status on IC, by the number of prior chemotherapy regimens and by histology.
An updated analysis with a total of 200 deaths observed and a median survival follow-up of 22 months showed a median OS of 12.6 months in patients treated with TECENTRIQ, vs. 9.7 months in patients treated with docetaxel (HR of 0.69, 95% CI: 0.52, 0.92). ORR was 15.3% vs. 14.7% and median DOR was 18.6 months vs. 7.2 months for TECENTRIQ vs. docetaxel, respectively.
About non-small cell lung cancer
Lung cancer is the leading cause of cancer death globally. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day. Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.
About the IMvigor211 study
IMvigor211 is a Phase III study of TECENTRIQ compared to chemotherapy in people with advanced bladder cancer who were previously treated with a platinum-based chemotherapy. The study evaluated the efficacy and safety of TECENTRIQ compared to chemotherapy of physician choice (vinflunine, paclitaxel or docetaxel) administered every three weeks in 931 people with previously-treated mUC who progressed during or following a platinum-based regimen. The primary efficacy endpoint was OS and key secondary endpoints include objective response rate, progression-free survival, duration of response and safety. IMvigor211 study did not meet its primary endpoint of overall survival (OS) compared to chemotherapy. These data were presented in full at the EACR-AACR-SIC Special Conference 2017.
The primary efficacy endpoint, overall survival, was to be tested in a successive fashion (hierarchical testing) in study populations defined by PD-L1 expression. The first population tested was people with the highest levels of PD-L1 expression (IC2/3), followed by those with any observable level of PD-L1 expression (IC1/2/3), and followed by the overall study population (Intention-To-Treat; ITT). Per the pre-specified hierarchical testing order, the IC2/3 (≥5%) population was tested first, with an OS HR of 0.87 (95% CI: 0.63, 1.21; median OS of 11.1 vs. 10.6 months for TECENTRIQ and chemotherapy respectively). In the overall study population (intention-to-treat or ITT) people treated with TECENTRIQ achieved a mOS of 8.6 months (CI: 95%; 7.8, 9.6) compared to 8.0 months (CI: 95%; 7.2, 8.6) with chemotherapy (HR 0.85, 95% CI 0.73-0.99).
Statistical significance needed to be achieved for the study populations in the following order: IC2/3 (≥5%), IC1/2/3 (≥1%), and ITT group. However, because statistical significance was not achieved for OS in the IC2/3 population, results could not be evaluated for statistical significance in the IC1/2/3 and ITT populations and those analyses are considered descriptive in nature.
Overall Response Rates (ORR) were similar to those previously reported in the phase II IMvigor210 study and similar between the two study arms. The median duration of response (mDOR), a secondary endpoint, for those receiving TECENTRIQ was 21.7 months (95% CI: 13.0, 21.7) in the overall study population, compared to 7.4 months (95% CI: 6.1, 10.3) for those receiving chemotherapy. At the time of data cutoff, the majority (63%) of people who responded to treatment with TECENTRIQ continued to respond, compared to 21% of people treated with chemotherapy.
About the IMvigor210 study (Cohort 2)
In Cohort 2, the co-primary efficacy endpoints were confirmed ORR as assessed by an IRF using RECIST v1.1 and investigator-assessed ORR according to Modified RECIST (mRECIST) criteria. There were 310 patients treated with TECENTRIQ 1,200 mg by intravenous infusion every 3 weeks until loss of clinical benefit. The study met its co-primary endpoints in Cohort 2, demonstrating statistically significant ORRs per IRF-assessed RECIST v1.1 and investigator-assessed mRECIST compared to a pre-specified historical control response rate of 10%.
An analysis was also performed with a median duration of survival follow-up of 21.1 months for Cohort 2. The confirmed ORRs per IRF-RECIST v1.1 were 28.0% (95% CI: 19.5, 37.9) in patients with PD-L1 expression IC2/3 (≥ 5%), 19.3% (95% CI: 14.2, 25.4) in patients with PD-L1 expression IC1/2/3 (≥ 1%), and 15.8% (95% CI: 11.9, 20.4) in all comers. The confirmed ORR per investigator-assessed mRECIST was 29.0% (95% CI: 20.4, 38.9) in patients with PD-L1 expression ≥ 5%, 23.7% (95% CI: 18.1, 30.1) in patients with PD-L1 expression ≥ 1%, and 19.7% (95% CI: 15.4, 24.6) in all comers. The rate of complete response per IRF-RECIST v1.1 in the all comer population was 6.1% (95% CI: 3.7, 9.4). For Cohort 2, median DOR per IRF-RECIST v1.1 was not reached in any PD-L1 expression subgroup or in all comers, however was reached in patients with PD-L1 expression < 1% (13.3 months; 95% CI 4.2, NE). The OS rate at 12 month was 37% in all comers.
About the IMvigor210 study (Cohort 1)
The positive CHMP opinion for patients who are ineligible for cisplatin-based chemotherapy is based on results from Cohort 1, which consisted of 119 people with locally advanced or mUC who were ineligible for cisplatin-containing chemotherapy and were either previously untreated or had disease progression at least 12 months after neoadjuvant (before surgery) or adjuvant (after surgery) chemotherapy. The primary endpoint of the study was objective response rate (ORR).

CI=confidence interval; DOR=duration of response; IC= tumour-infiltrating immune cells; IRF= independent review facility; NE=not estimable; ORR=objective response rate; OS=overall survival; PFS=progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumours v1.1.
Pooled Safety Profile
The safety of TECENTRIQ is based on pooled data in 2,160 patients with mUC and NSCLC. The most common adverse all grade reactions were fatigue (35.4%), decreased appetite (25.5%), nausea (22.9%), dyspnoea (21.8%), diarrhoea (18.6%), pyrexia (18.3%), rash (18.6%), vomiting (15.0%), arthralgia (14.2%), asthenia (13.8%) and pruritus (11.3%).
About metastatic urothelial carcinoma
Metastatic urothelial carcinoma (mUC) is associated with a poor prognosis and limited treatment options. It is a disease that has seen no major advances for more than 30 years outside of the US. UC is the ninth most common cancer worldwide, with 430,000 new cases diagnosed in 2012, and it results in approximately 145,000 deaths globally each year. Men are three times more likely to suffer from UC, compared with women, and the disease is three times more common in developed countries than in less developed countries.
About TECENTRIQ (atezolizumab)
TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1. TECENTRIQ is designed to bind to PD-L1 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 has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers
About Roche in cancer immunotherapy