On September 05 2018, Roche reported that it was notified by the U.S. Food and Drug Administration (FDA) that the review period for the supplemental Biologics License Application (sBLA) for TECENTRIQ (atezolizumab) in combination with Avastin (bevacizumab), carboplatin and paclitaxel for the initial treatment of people with metastatic non-squamous non-small cell lung cancer (NSCLC) has been extended by three months (Press release, Hoffmann-La Roche, SEP 5, 2018, View Source [SID1234529354]). The extension allows the FDA time to review additional information requested in support of the sBLA. FDA determined that the submission of this information constituted a major amendment to the sBLA resulting in this extension of the PDUFA goal date. The FDA is expected to make a decision on approval by December 05, 2018. In May 2018, TECENTRIQ in combination with Avastin, carboplatin and paclitaxel was granted Priority Review from the FDA for the initial treatment of people with metastatic non-squamous NSCLC based on results from the Phase III IMpower150 study.

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About NSCLC
Lung cancer is the leading cause of cancer death globally.[1] Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.[2] 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.[2] NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope. The squamous form tends to grow near the centre of the lung, and accounts for approximately 25-30% of all NSCLC cases.[3]

About TECENTRIQ
TECENTRIQ is a monoclonal antibody designed to bind with a protein called 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.

Currently, Roche has eight Phase III lung cancer studies underway, evaluating TECENTRIQ alone or in combination with other medicines.

TECENTRIQ is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC).

About Avastin (bevacizumab)
Avastin is a biologic cancer treatment approved across several types of cancers including advanced stages of breast cancer, colorectal cancer, non-small cell lung cancer, kidney cancer, ovarian cancer and cervical cancer, and recurrent glioblastoma. Avastin is approved in combination with chemotherapy for the first-line treatment of advanced NSCLC and, to-date, has helped over 500,000 patients lead longer lives. Avastin is considered a standard of care for the first-line treatment of advanced NSCLC and has been proven to significantly extend overall survival (OS). Avastin is currently approved in combination with any platinum-based chemotherapy in Europe, and with paclitaxel/carboplatin in the US, in first-line non-squamous NSCLC, based on results of the pivotal Phase III E4599 study. Avastin was the first medicine to help people with previously untreated advanced, non-squamous NSCLC live longer (OS) than one year when added to chemotherapy.

About the TECENTRIQ (atezolizumab) and Avastin (bevacizumab) combination
There is a strong scientific rationale to support combining TECENTRIQ and Avastin. The TECENTRIQ and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers, including first-line advanced NSCLC. Avastin, in addition to its established anti-angiogenic effects, may further enhance TECENTRIQ’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

On September 5, 2018 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the China National Medical Products Administration (NMPA) approved the kinase inhibitor LENVIMA (lenvatinib) as a single agent for the treatment of patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy (Press release, Eisai, SEPT 5, 2018, View Source [SID1234529296]). In China, the application of LENVIMA was submitted in October 2017 and was designated for Priority Review by the NMPA due to LENVIMA’s significant clinical benefit compared to existing treatments, leading to approval in approximately 10 months. This approval marks the first for LENVIMA in China, where the incidence of HCC is high, and the first new systemic therapy approved for the first-line treatment of unresectable HCC in China in ten years.

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"Over the past decade, there have been limited treatment options available for patients with unresectable HCC," said Dr. Takashi Owa, Vice President and Chief Medicine Creation Officer, Oncology Business Group, Eisai. "We are pleased to be able to deliver LENVIMA to HCC patients in China, and we are thankful for the collaborative efforts by regulatory and government authorities, as well as the patients and physicians who participated in the clinical studies and made this approval possible."

"Today’s milestone for LENVIMA is an important one for patients in China living with unresectable HCC, which is historically difficult to treat and has a poor prognosis," said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. "Merck remains committed to bringing new treatment advances to patients in China. The approval of LENVIMA, through our collaboration with Eisai, is the third cancer medicine in our portfolio to be approved in China this year – reinforcing the great progress being made to bring new treatment options forward for Chinese patients."

The approval was based on results from the REFLECT study (Study 304), an open-label, Phase 3 trial where LENVIMA demonstrated a treatment effect on overall survival (OS) by statistical confirmation of non-inferiority when compared with the standard of care, sorafenib, in 954 patients with previously untreated unresectable HCC; patients randomized to the LENVIMA arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. LENVIMA demonstrated statistically significant superiority and clinically meaningful improvements in progression-free survival (PFS), time to progression (TTP) and objective response rate (ORR). In a subpopulation analysis of 288 patients in the study from the greater Chinese region (mainland China, Hong Kong and Taiwan), LENVIMA demonstrated efficacy based on non-inferiority of OS compared to sorafenib, with improvements also observed in PFS, TTP and ORR. Approximately 80% of patients in the subpopulation were living with HCC resulting from chronic hepatitis B virus (HBV), which has high unmet medical need. For these patients, LENVIMA demonstrated non-inferiority based on OS compared with sorafenib, thereby demonstrating the effect of LENVIMA in patients with HCC resulting from HBV.

In the China package insert, the five most common adverse reactions observed in patients treated with LENVIMA were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%) and decreased weight (31%), which is consistent with the known side-effect profile of LENVIMA.

Liver cancer is the second leading cause of cancer-related deaths and is estimated to be responsible for approximately 750,000 deaths per year globally. Additionally, approximately 780,000 cases are newly diagnosed each year, about 80% of which occur in Asian regions. Specifically, in China, there are approximately 395,000 new cases and 380,000 deaths per year, accounting for approximately 50% of cases worldwide. HCC accounts for 85% to 90% of primary liver cancer cases. Unresectable HCC, for which treatment options are limited, is extremely difficult to treat, and the development of new treatments is necessary.

Since the initial launch, more than 10,000 patients have been treated with LENVIMA. Today, LENVIMA is approved as a treatment for refractory thyroid cancer in over 50 countries including the United States, Japan, in Europe and Asia, and as combination with everolimus as a second-line treatment for renal cell carcinoma (RCC) in over 45 countries including the United States and in Europe. For HCC, LENVIMA was approved for use in Japan in March 2018, and in the United States and Europe in August 2018. In Japan, approximately 3,000 HCC patients have been treated with LENVIMA since approval of this indication.

About the REFLECT Trial (Study 304)

REFLECT was a large (n=954) Phase 3, randomized, multicenter, open-label trial conducted by Eisai to compare the efficacy and safety of LENVIMA versus sorafenib as a first-line systemic treatment in patients with unresectable HCC. Patients at 154 trial sites in 20 countries were randomized to receive LENVIMA 12 mg or 8 mg once a day depending on body weight (≥60 kg or <60 kg, respectively) (n=478) or sorafenib 400 mg twice a day (n=476). Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of this study was OS, tested first for non-inferiority to sorafenib, then for superiority. The key secondary efficacy endpoints of this study included PFS, TTP and ORR, tested for superiority to sorafenib.

In the China package insert, REFLECT showed that LENVIMA achieved the primary endpoint, demonstrating a treatment effect on OS by statistical confirmation of non-inferiority to sorafenib. Patients treated with LENVIMA experienced a median OS of 13.6 months compared to 12.3 months with sorafenib (Hazard Ratio [HR]: 0.92; 95% Confidence Interval [CI]: 0.79-1.06). Patients randomized to the LENVIMA arm did not have a statistically significant improvement in OS compared to those in the sorafenib arm. In addition, LENVIMA showed statistically significant superiority and clinically meaningful improvements in the secondary efficacy endpoints of PFS, TTP and ORR, as confirmed by a blinded independent imaging review:

Median PFS was doubled with LENVIMA compared to sorafenib: 7.3 months versus 3.6 months (HR: 0.64; 95% CI: 0.55–0.75; p<0.00001) per blinded independent imaging review based on mRECIST criteria.
Median TTP was doubled with LENVIMA compared to sorafenib: 7.4 months versus 3.7 months (HR: 0.60; 95% CI: 0.51–0.71; p<0.00001) per blinded independent imaging review based on mRECIST criteria.
LENVIMA showed nearly 3.5 times the ORR of sorafenib: 40.6% (95% CI: 36.2-45.0) versus 12.4% (95% CI: 9.4-15.4) per blinded independent imaging review based on mRECIST criteria (odds ratio 5.01; 95% CI: 3.59-7.01; p<0.00001).
About the Subpopulation Analysis of Patients from the Greater Chinese Region

The results of subpopulation analysis of patients from the greater Chinese region were based on 288 patients out of the 954 HCC patients who participated in the REFLECT study. In this subpopulation analysis, median OS was 15.0 months for LENVIMA versus 10.2 months for sorafenib (HR: 0.73; 95% CI: 0.55-0.96; nominal p=0.02620). Independent imaging review based on mRECIST criteria revealed the following results: PFS (LENVIMA 8.4 months versus sorafenib 3.6 months in median [HR: 0.47; 95% CI: 0.35-0.64; nominal p<0.00001]), TTP (LENVIMA 9.2 months versus sorafenib 3.6 months in median [HR: 0.45; 95% CI: 0.33-0.62; nominal p<0.00001]) and ORR (LENVIMA 43.8% versus sorafenib 13.2% [odds ratio 5.14; 95% CI: 2.84-9.31; nominal p<0.00001]).

Additionally, of the 288 patients in the subpopulation, approximately 80% (n=242) were living with HCC resulting from HBV. An analysis of these patients revealed the following results for OS: LENVIMA (n=123) 14.9 months versus sorafenib (n=119) 9.9 months in median (HR: 0.72; 95% CI: 0.53-0.97).

About Unresectable Hepatocellular Carcinoma (HCC)

Liver cancer is the second leading cause of cancer-related deaths and is estimated to be responsible for 750,000 deaths per year globally. Additionally, 780,000 cases are newly diagnosed each year. There is a large regional difference, with about 80% of new cases occurring in Asian regions, including China and Japan. HCC accounts for 85% to 90% of primary liver cancer cases. HCC is associated with chronic liver disease, in particular cirrhosis. Major causes of cirrhosis include hepatitis B virus and hepatitis C virus. However, according to a recent investigation, non-B/non-C HCC is on the rise. Surgery is the first option for treatment, but for patients with unresectable HCC who are not amenable for potentially curative therapeutic interventions, which include liver transplant, surgical resection and tumor ablation (typically radiofrequency ablation or cryotherapy), or who are not suitable for transarterial chemoembolization (TACE), treatment options are limited and the prognosis is very poor.

About LENVIMA (lenvatinib) capsules 10 mg and 4 mg

LENVIMA (lenvatinib) is a kinase inhibitor that is indicated in the U.S.:

For the treatment of patients with locally recurrent or metastatic, progressive radioactive iodine-refractory differentiated thyroid cancer (DTC)
In combination with everolimus, for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)
LENVIMA, discovered and developed by Eisai, is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2α (FRS2α) phosphorylation.

Important Safety Information in the U.S.

Warnings and Precautions

Hypertension. In DTC, hypertension occurred in 73% of patients on LENVIMA (44% grade 3-4). In RCC, hypertension occurred in 42% of patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure ≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood pressure ≥100 mmHg. In HCC, hypertension occurred in 45% of LENVIMA-treated patients (24% grade 3). Grade 4 hypertension was not reported in HCC.

Serious complications of poorly controlled hypertension have been reported. Control blood pressure prior to initiation. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at reduced dose when hypertension is controlled or permanently discontinue based on severity.

Cardiac Dysfunction. Serious and fatal cardiac dysfunction can occur with LENVIMA. Across clinical trials in 799 patients with DTC, RCC, and HCC, grade 3 or higher cardiac dysfunction occurred in 3% of LENVIMA-treated patients. Monitor for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Arterial Thromboembolic Events. Among patients receiving LENVIMA or LENVIMA + everolimus, arterial thromboembolic events of any severity occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials.

Permanently discontinue following an arterial thrombotic event. The safety of resuming after an arterial thromboembolic event has not been established and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.

Hepatotoxicity. Across clinical studies enrolling 1,327 LENVIMA-treated patients with malignancies other than HCC, serious hepatic adverse reactions occurred in 1.4% of patients. Fatal events, including hepatic failure, acute hepatitis and hepatorenal syndrome, occurred in 0.5% of patients. In HCC, hepatic encephalopathy occurred in 8% of LENVIMA-treated patients (5% grade 3-5). Grade 3-5 hepatic failure occurred in 3% of LENVIMA-treated patients. 2% of patients discontinued LENVIMA due to hepatic encephalopathy and 1% discontinued due to hepatic failure.

Monitor liver function prior to initiation, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Renal Failure or Impairment. Serious including fatal renal failure or impairment can occur with LENVIMA. Renal impairment was reported in 14% and 7% of LENVIMA-treated patients in DTC and HCC, respectively. Grade 3-5 renal failure or impairment occurred in 3% of patients with DTC and 2% of patients with HCC, including 1 fatal event in each study. In RCC, renal impairment or renal failure was reported in 18% of LENVIMA + everolimus–treated patients (10% grade 3).

Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at reduced dose upon recovery or permanently discontinue for renal failure or impairment based on severity.

Proteinuria. In DTC and HCC, proteinuria was reported in 34% and 26% of LENVIMA-treated patients, respectively. Grade 3 proteinuria occurred in 11% and 6% in DTC and HCC, respectively. In RCC, proteinuria occurred in 31% of patients receiving LENVIMA + everolimus (8% grade 3).

Monitor for proteinuria prior to initiation and periodically during treatment. If urine dipstick proteinuria ≥2+ is detected, obtain a 24-hour urine protein. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Diarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC, diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81% of LENVIMA + everolimus–treated patients (19% grade 3). Diarrhea was the most frequent cause of dose interruption/reduction, and diarrhea recurred despite dose reduction.

Promptly initiate management of diarrhea. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Fistula Formation and Gastrointestinal Perforation. Of the 799 patients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and HCC, fistula or gastrointestinal perforation occurred in 2%. Fistulas and gastrointestinal perforations have also been reported in other lenvatinib clinical trials and in post-marketing experience. Pneumothorax has been reported with and without clear evidence of a bronchopleural fistula. Some reports of gastrointestinal perforation, fistula, and pneumothorax occurred in association with tumor regression or necrosis. In most cases of fistula formation or gastrointestinal perforation, risk factors such as prior surgery or radiotherapy were present.

Permanently discontinue in patients who develop gastrointestinal perforation of any severity or grade 3-4 fistula.

QT Interval Prolongation. In DTC, QT/QTc interval prolongation occurred in 9% of LENVIMA-treated patients and QT interval prolongation of >500 ms occurred in 2%. In RCC, QTc interval increases of >60 ms occurred in 11% of patients receiving LENVIMA + everolimus and QTc interval >500 ms occurred in 6%. In HCC, QTc interval increases of >60 ms occurred in 8% of LENVIMA-treated patients and QTc interval >500 ms occurred in 2%.

Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at reduced dose upon recovery based on severity.

Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of LENVIMA-treated patients. In 65% of cases, hypocalcemia improved or resolved following calcium supplementation with or without dose interruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred in 6% of LENVIMA + everolimus–treated patients. In HCC, grade 3 hypocalcemia occurred in 0.8% of LENVIMA-treated patients.

Monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity.

Reversible Posterior Leukoencephalopathy Syndrome. Across clinical studies of 1,823 patients who received LENVIMA as a single agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity and persistence of neurologic symptoms.

Hemorrhagic Events. Serious including fatal hemorrhagic events can occur with LENVIMA. In DTC, RCC, and HCC clinical trials, hemorrhagic events, of any grade, occurred in 29% of the 799 patients treated with LENVIMA as a single agent or in combination with everolimus. The most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and hematuria. In DTC, grade 3-5 hemorrhage occurred in 2% of LENVIMA-treated patients, including 1 fatal intracranial hemorrhage among 16 patients who received LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5 hemorrhage occurred in 8% of LENVIMA + everolimus–treated patients, including 1 fatal cerebral hemorrhage. In HCC, grade 3-5 hemorrhage occurred in 5% of LENVIMA-treated patients, including 7 fatal hemorrhagic events.

Serious tumor-related bleeds, including fatal hemorrhagic events, occurred in LENVIMA-treated patients in clinical trials and in the postmarketing setting. In postmarketing surveillance, serious and fatal carotid artery hemorrhages were seen more frequently in patients with anaplastic thyroid carcinoma (ATC) than other tumors. Safety and effectiveness of LENVIMA in patients with ATC have not been demonstrated in clinical trials.

Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction. LENVIMA impairs exogenous thyroid suppression. In DTC, 88% of patients had baseline thyroid stimulating hormone (TSH) level ≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated patients. In RCC and HCC, grade 1 or 2 hypothyroidism occurred in 24% of LENVIMA + everolimus–treated patients and 21% of LENVIMA-treated patients, respectively. In patients with normal or low TSH at baseline, elevation of TSH was observed post baseline in 70% of LENVIMA-treated patients in HCC and 60% of LENVIMA + everolimus–treated patients in RCC.

Monitor thyroid function prior to initiation and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.

Wound Healing Complications. Wound healing complications, including fistula formation and wound dehiscence, can occur with LENVIMA. Withhold for at least 6 days prior to scheduled surgery. Resume after surgery based on clinical judgment of adequate wound healing. Permanently discontinue in patients with wound healing complications.

Embryo-fetal Toxicity. Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to pregnant women. In animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended clinical doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits. Advise pregnant women of the potential risk to a fetus; and advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 30 days after the last dose.

Adverse Reactions

In DTC, the most common adverse reactions (≥30%) observed in LENVIMA-treated patients were hypertension (73%), fatigue (67%), diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%), decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%), vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia syndrome (32%), abdominal pain (31%), and dysphonia (31%). The most common serious adverse reactions (≥2%) were pneumonia (4%), hypertension (3%), and dehydration (3%). Adverse reactions led to dose reductions in 68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most common adverse reactions (≥10%) resulting in dose reductions were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); the most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were hypertension (1%) and asthenia (1%).

In RCC, the most common adverse reactions (≥30%) observed in LENVIMA + everolimus–treated patients were diarrhea (81%), fatigue (73%), arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%), nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema (42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%), decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%). The most common serious adverse reactions (≥5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose reductions or interruption in 89% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%). Treatment discontinuation due to an adverse reaction occurred in 29% of patients.In HCC, the most common adverse reactions (≥20%) observed in LENVIMA-treated patients were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%), decreased weight (31%), abdominal pain (30%), palmar-plantar erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia (24%), hemorrhagic events (23%), hypothyroidism (21%), and nausea (20%). The most common serious adverse reactions (≥2%) were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%), and decreased appetite (2%). Adverse reactions led to dose reductions or interruption in 62% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were fatigue (9%), decreased appetite (8%), diarrhea (8%), proteinuria (7%), hypertension (6%), and palmar-plantar erythrodysesthesia syndrome (5%). Treatment discontinuation due to an adverse reaction occurred in 20% of patients. The most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were fatigue (1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic failure (1%).

Use in Specific Populations

Because of the potential for serious adverse reactions in breastfed infants, advise women to discontinue breastfeeding during treatment and for at least 1 week after last dose. LENVIMA may impair fertility in males and females of reproductive potential.

No dose adjustment is recommended for patients with mild (CLcr 60-89 mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. LENVIMA concentrations may increase in patients with DTC or RCC and severe (CLcr 15-29 mL/min) renal impairment. Reduce the dose for patients with RCC or DTC and severe renal impairment. There is no recommended dose for patients with HCC and severe renal impairment. LENVIMA has not been studied in patients with end stage renal disease.

No dose adjustment is recommended for patients with HCC and mild hepatic impairment (Child-Pugh A). There is no recommended dose for patients with HCC with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.

No dose adjustment is recommended for patients with DTC or RCC and mild or moderate hepatic impairment. LENVIMA concentrations may increase in patients with DTC or RCC and severe hepatic impairment. Reduce the dose for patients with DTC or RCC and severe hepatic impairment.

On September 5, 2018 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that new data from its broad clinical development program across different types of lung cancer will be presented at the International Association for the Study of Lung Cancer (IASLC) 2018 World Conference on Lung Cancer (WCLC), taking place from September 23-26 in Toronto, Canada (Press release, Genentech, SEP 5, 2018, View Source [SID1234529319]). Ten abstracts have been accepted, including three ‘late breakers’ and five oral presentations.

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"We look forward to presenting new data from our comprehensive lung cancer program, including new immunotherapy and targeted treatment strategies across different types of lung cancer," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "We are particularly pleased to be sharing positive TECENTRIQ data in extensive-stage small cell lung cancer, which has seen limited progress in treatment over the last two decades, as well as new pivotal data for our investigational therapy entrectinib for the treatment of ROS1 fusion-positive lung cancer."

Key presentations

Progression-free survival (PFS) and overall survival (OS) data from the Phase III IMpower133 study of TECENTRIQ plus chemotherapy (carboplatin and etoposide) for the initial (first-line) treatment of people with extensive-stage small cell lung cancer (ES-SCLC) will be presented in the Presidential Symposium. These are the first positive survival data from a Phase III study with an immunotherapy-based combination in the initial treatment of ES-SCLC.

PFS and OS data will be presented from the Phase III IMpower132 study investigating TECENTRIQ plus pemetrexed and platinum-based chemotherapy (cisplatin or carboplatin) in the initial treatment of people with advanced non-squamous non-small cell lung cancer (NSCLC). The IMpower132 and IMpower133 data will be featured as part of WCLC’s official press program on Monday, September 24 and Tuesday, September 25, respectively.

Additionally, results from a Phase Ib study investigating Tarceva plus TECENTRIQ in tyrosine kinase inhibitor (TKI)-naïve people with EGFR mutation-positive NSCLC will also be presented.

New pivotal results of entrectinib, an investigational oral treatment for people with locally advanced or metastatic ROS1 fusion-positive NSCLC, from a pooled analysis including the global Phase II STARTRK-2 basket study will be presented. These data have also been selected to be featured in the WCLC press program on Monday, September 24.

Follow Genentech on Twitter via @Genentech and keep up to date with WCLC 2018 congress news and updates by using the hashtag #WCLC2018.

For more information on Genentech’s approach to cancer, visit View Source

Overview of key presentations featuring Genentech medicines at WCLC 2018

Medicine
Abstract title
Abstract number
Entrectinib

Efficacy and safety of entrectinib in locally advanced or metastatic ROS1 fusion-positive NSCLC
OA02.01 Oral
Monday, Sept. 24
10:30 – 10:40 a.m. EDT
TECENTRIQ (atezolizumab)
IMpower133: Primary PFS, OS and safety in a Phase 1/3 study of 1L atezolizumab plus carboplatin and etoposide in extensive-stage SCLC
PL02.07 Oral
Tuesday, Sept. 25
9:00 – 9:10 a.m. EDT
TECENTRIQ (atezolizumab)
IMpower132: PFS, OS and safety results of 1L atezolizumab plus carboplatin/cisplatin plus pemetrexed in stage IV non-squamous NSCLC
OA05.07 Oral
Monday, Sept. 24
2:35 – 2:45 p.m. EDT
TECENTRIQ (atezolizumab)
Comprehensive peripheral blood immunophenotyping and T-cell clonal analysis during neoadjuvant immunotherapy with atezolizumab in NSCLC
MA04.10 Mini Oral
Monday, Sept. 24
2:35 – 2:40 p.m. EDT
TECENTRIQ (atezolizumab)
Neoadjuvant atezolizumab in resectable non-small cell lung cancer (NSCLC): updated results from a multicenter study
MA04.09 Mini Oral
Monday, Sept. 24
2:30 – 2:35 p.m. EDT
TECENTRIQ (atezolizumab)
Tarceva
(erlotinib)
Long-term safety and clinical activity results from a Phase 1b of erlotinib plus atezolizumab in advanced NSCLC
MA15.02 Mini Oral
Tuesday, Sept. 25
1:35 – 1:40 p.m. EDT
TECENTRIQ (atezolizumab)
Avastin (bevacizumab)
IMpower150: Impact of chemotherapy cycles in 1L metastatic NSCLC in patients treated with atezolizumab and bevacizumab
P1.01-83 Poster
Monday, Sept. 24
4:45 – 6:00 p.m. EDT
TECENTRIQ (atezolizumab)
Retrospective descriptive analysis of metformin with atezolizumab in advanced non-small cell lung cancer in the OAK trial
P1.04-33 Poster
Monday, Sept. 24
4:45 – 6:00 p.m. EDT
TECENTRIQ (atezolizumab)
IMpower030: Phase III study evaluating neoadjuvant treatment of resectable stage II-IIIB NSCLC with atezolizumab plus chemotherapy
P2.17-27 Poster
Tuesday, Sept. 25
4:45 – 6:00 p.m. EDT
TECENTRIQ (atezolizumab)
Cost-effectiveness of atezolizumab for previously treated advanced or metastatic non-small cell lung cancer (NSCLC) in Canada
P3.04-17 Poster
Wednesday, Sept. 26
12:00 – 1:00 p.m. EDT
About lung cancer

According to the American Cancer Society, it is estimated that more than 234,000 Americans will be diagnosed with lung cancer in 2018. Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most prevalent type, accounting for around 85 percent of all lung cancer cases, and SCLC accounting for approximately 15 percent of all cases. It is estimated that approximately 60 percent of lung cancer diagnoses in the United States are made when the disease is in the advanced stages. While the ROS1 gene fusion can be found in any person with NSCLC, young never-smokers have the highest incidence of ROS1-positive NSCLC.

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 tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the re-activation of T cells. TECENTRIQ may also affect normal cells.

TECENTRIQ U.S. Indication (pronounced ‘tē-SEN-trik’)

TECENTRIQ is a prescription medicine used to treat:

A type of bladder and urinary tract cancer called urothelial carcinoma.

TECENTRIQ may be used when your bladder cancer:
has spread or cannot be removed by surgery, and if you have any one of the following conditions:
you are not able to take chemotherapy that contains a medicine called cisplatin, and your doctor has tested your cancer and found high levels of a specific protein on your cancer called programmed death-ligand 1 (PD-L1), as determined by an FDA-approved test, or
you are not able to take chemotherapy that contains any platinum regardless of PD-L1 status on your cancer, or
you have tried chemotherapy that contains platinum, and it did not work or is no longer working
The approval of TECENTRIQ in these patients is based on a study that measured response rate and duration of response. There is an ongoing study to confirm clinical benefit.

A type of lung cancer called non-small cell lung cancer (NSCLC).

TECENTRIQ may be used when your lung cancer:
has spread or grown, and
you have tried chemotherapy that contains platinum, and it did not work or is no longer working
If your tumor has an abnormal EGFR or ALK gene, you should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working.

It is not known if TECENTRIQ is safe and effective in children.

Important Safety Information

What is the most important information about TECENTRIQ?

TECENTRIQ can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life threatening and can lead to death.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

TECENTRIQ can cause serious side effects, including:

Lung problems (pneumonitis) –signs and symptoms may include new or worsening cough, shortness of breath, and chest pain
Liver problems (hepatitis) –signs and symptoms of hepatitis may include yellowing of the skin or the whites of the eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual
Intestinal problems (colitis) –signs and symptoms of colitis may include diarrhea (loose stools) or more bowel movements than usual, blood or mucous in the stools or dark, tarry, sticky stools, and severe stomach area (abdomen) pain or tenderness
Hormone gland problems (especially the thyroid, adrenal glands, pancreas, and pituitary) –signs and symptoms that the hormone glands are not working properly may include headaches that will not go away or unusual headaches, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, changes in mood or behavior (such as decreased sex drive, irritability, or forgetfulness), feeling cold, constipation, the voice gets deeper, urinating more often than usual, nausea or vomiting, and stomach area (abdomen) pain
Problems in other organs –signs and symptoms may include severe muscle weakness, numbness or tingling in hands or feet, confusion, blurry vision, double vision, or other vision problems, changes in mood or behavior, extreme sensitivity to light, neck stiffness, eye pain or redness, skin blisters or peeling, chest pain, irregular heartbeat, shortness of breath, or swelling of the ankles
Severe infections –signs and symptoms of infection may include fever, cough, flu-like symptoms, pain when urinating, and frequent urination or back pain
Severe infusion reactions –signs and symptoms of infusion reactions may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, swelling of the face or lips, dizziness, fever, feeling like passing out, and back or neck pain
Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with TECENTRIQ if patients have severe side effects.

Before receiving TECENTRIQ, patients should tell their healthcare provider about all of their medical conditions, including if they:

have immune system problems (such as Crohn’s disease, ulcerative colitis, or lupus); have had an organ transplant; have lung or breathing problems; have liver problems; have a condition that affects the nervous system (such as myasthenia gravis or Guillain-Barre syndrome); or are being treated for an infection
are pregnant or plan to become pregnant. TECENTRIQ can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with TECENTRIQ. If patients are able to become pregnant:
A healthcare provider should do a pregnancy test before they start treatment with TECENTRIQ.
They should use an effective method of birth control during their treatment and for at least 5 months after the last dose of TECENTRIQ.
are breastfeeding or plan to breastfeed. It is not known if TECENTRIQ passes into the breast milk. Do not breastfeed during treatment and for at least 5 months after the last dose of TECENTRIQ
Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of TECENTRIQ in people with urothelial carcinoma include:

feeling tired
decreased appetite
nausea
constipation
urinary tract infection
diarrhea
fever
The most common side effects of TECENTRIQ in people with non-small cell lung cancer include:

feeling tired
decreased appetite
muscle pain
cough
shortness of breath
TECENTRIQ may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of TECENTRIQ. Patients should ask their healthcare provider or pharmacist for more information. Patients should call their doctor for medical advice about side effects.

Report side effects to the FDA at 1-800-FDA-1088 or View Source Report side effects to Genentech at 1-888-835-2555.

Please visit View Source for the TECENTRIQ full Prescribing Information for additional Important Safety Information.

About Avastin (bevacizumab)

Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor (VEGF) that plays an important role throughout the lifecycle of the tumor to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumor blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumor blood supply is thought to be critical to a tumor’s ability to grow and spread in the body (metastasize).

Avastin Indications:

Metastatic colorectal cancer (mCRC) for first- or second-line treatment in combination with intravenous 5-fluorouracil–based chemotherapy. It is also approved to treat mCRC for second-line treatment, when used with fluoropyrimidine-based (combined with irinotecan or oxaliplatin) chemotherapy, after cancer progresses following a first-line treatment that includes Avastin.
Avastin is not approved for use after the primary treatment of colon cancer that has not spread to other parts of the body
Advanced nonsquamous non–small cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel, in people who have not received chemotherapy for their advanced disease
Metastatic kidney cancer (mRCC) when used with interferon alfa
Glioblastoma (GBM) in adult patients whose cancer has progressed after prior treatment (recurrent or rGBM)
Advanced cervical cancer (CC) in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is approved to treat persistent, recurrent, or metastatic cancer of the cervix
Ovarian cancer (OC). Avastin, in combination with carboplatin and paclitaxel, followed by Avastin alone, is used for the treatment of patients with advanced (Stage III or IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgery.
Avastin in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan, is approved to treat platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer (prOC) in women who received no more than two prior chemotherapy treatments.

Avastin, either in combination with carboplatin and paclitaxel or with carboplatin and gemcitabine, followed by Avastin alone, is approved for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer (psOC)

Possible serious side effects

Everyone reacts differently to Avastin therapy. So, it’s important to know what the side effects are. Although some people may have a life-threatening side effect, most do not . Their doctor will stop treatment if any serious side effects occur.

Patients should contact their health care team if there are any signs of these side effects.

Most serious side effects (not common, but sometimes fatal):

GI perforation. A hole that develops in the stomach or intestine. Symptoms include pain in the abdomen, nausea, vomiting, constipation, or fever
Wounds that don’t heal. A cut made during surgery can be slow to heal or may not fully heal. Avastin should not be used for at least 28 days before or after surgery and until surgical wounds are fully healed
Serious bleeding. This includes vomiting or coughing up blood; bleeding in the stomach, brain, or spinal cord; nosebleeds; and vaginal bleeding. If a patient has recently coughed up blood or had serious bleeding, they should be sure to tell their doctor
Other possible serious side effects

Abnormal passage in the body. This type of passage—known as a fistula—is an irregular connection from one part of the body to another and can sometimes be fatal
Severe high blood pressure. Blood pressure that severely spikes or shows signs of affecting the brain. Blood pressure should be monitored every 2 to 3 weeks while on Avastin and after stopping treatment
Kidney problems. These may be caused by too much protein in the urine and can sometimes be fatal
Infusion reactions. These were uncommon with the first dose (less than 3% of patients). 0.2% of patients had severe reactions. Infusion reactions include high blood pressure or severe high blood pressure that may lead to stroke, trouble breathing, decreased oxygen in red blood cells, a serious allergic reaction, chest pain, headache, tremors, and excessive sweating. The patient’s doctor or nurse will monitor for signs of infusion reactions
Severe stroke or heart problems. These may include blood clots, mini-stroke, heart attack, chest pain, and the heart may become too weak to pump blood to other parts of the body (congestive heart failure). These can sometimes be fatal
Nervous system and vision problems. Signs include headache, seizure, high blood pressure, sluggishness, confusion, and blindness
Side effects seen most often

In clinical studies across different types of cancer, some patients experienced the following side effects:

High blood pressure
Too much protein in the urine
Nosebleeds
Rectal bleeding
Back pain
Headache
Taste change
Dry skin
Inflammation of the skin
Inflammation of the nose
Watery eyes
Avastin is not for everyone

Patients should talk to their doctor if they are:

Undergoing surgery. Avastin should not be used for 28 days before or after surgery and until surgical wounds are fully healed
Pregnant or think they are pregnant. Data have shown that Avastin may harm a woman’s unborn baby. Birth control should be used while patients are on Avastin. If Avastin is stopped, patients should keep using birth control for 6 months before trying to become pregnant
Planning to become pregnant. Taking Avastin could cause a woman’s ovaries to stop working and may impair her ability to have children
Breastfeeding. Breastfeeding while on Avastin may harm the baby and is therefore not recommended during and for 6 months after taking Avastin
Patients should talk with their doctor if they have any questions about their condition or treatment.

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

For full Prescribing Information and Boxed WARNINGS on Avastin please visit View Source

About Tarceva (erlotinib)

Tarceva is a once-daily, oral non-chemotherapy medicine for the treatment of NSCLC whose cancer has spread to other parts of the body and that has certain types of EGFR mutations. It has been shown to inhibit EGFR, a protein involved in the growth and development of cancers. Tarceva is a trademark of OSI Pharmaceuticals, LLC, Farmingdale, NY, USA, an affiliate of Astellas Pharma US, Inc. In the United States, Tarceva is jointly marketed by Astellas and Genentech, a member of the Roche Group.

Tarceva Indication in NSCLC

Metastatic Non-Small Cell Lung Cancer (NSCLC):

Tarceva is prescribed for the treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test receiving first-line, maintenance, or second or greater line treatment after progression following at least one prior chemotherapy regimen.
Limitations of Use:

Safety and efficacy of Tarceva have not been established in patients with NSCLC whose tumors have other EGFR mutations.
Tarceva is not recommended for use in combination with platinum-based chemotherapy.
Important Safety Information

The following serious adverse reactions, which may include deaths, have been reported in patients taking Tarceva: Interstitial Lung Disease (ILD)-like events; Liver and/or kidney problems; Gastrointestinal (GI) perforations (the development of a hole in the stomach, small intestine, or large intestine); Serious skin conditions; Blood, bleeding and clotting problems (stroke); Eye disorders (dry eyes, eye irritation, and damage to the cornea); Bleeding events when taking warfarin or non-steroidal anti-inflammatory drugs (NSAIDs); Pregnancy (women should avoid becoming pregnant and avoid breastfeeding while taking Tarceva).

Patients should call their doctor right away if they have these signs or symptoms: Serious or ongoing diarrhea, nausea (feeling sick to the stomach), loss of appetite, or vomiting; New or worsening shortness of breath or cough; Eye irritation; New or worsening rash, blistering or skin peeling; Any changes in smoking habits.

The most common serious side effects include:

Diarrhea, weakness, rash, cough, shortness of breath, loss of appetite, nausea, and vomiting.

Patients should call their healthcare provider for medical advice about side effects.

Report side effects to the FDA at (800) FDA-1088 or View Source Patients and caregivers may also report side effects to Genentech at (888) 835-2555.

For full prescribing information, please call 1-877-TARCEVA or visit View Source

About entrectinib

Entrectinib (RXDX-101) is an investigational oral medicine in development for the treatment of locally advanced or metastatic solid tumors that harbor NTRK1/2/3 or ROS1 fusions. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRKA/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer. Entrectinib can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK fusions. Entrectinib is being investigated across a range of solid tumor types, including NSCLC, pancreatic cancer, sarcomas, thyroid cancer, salivary cancer, gastrointestinal stromal tumors (GIST) and cancers of unknown primary (CUP).

About Genentech in Personalized Cancer Immunotherapy

For more than 30 years, Genentech has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever to bring personalized cancer immunotherapy (PCI) to people with cancer. The goal of PCI is to provide each person with a treatment tailored to harness his or her own immune system to fight cancer. Genentech is studying more than 20 investigational medicines, 10 of which are in clinical trials. In every study we are evaluating biomarkers to identify which people may be appropriate candidates for our medicines. For more information visit View Source

On September 5, 2018 Checkmate Pharmaceuticals (Checkmate), reported that it has entered into a clinical trial collaboration and supply agreement with the alliance between Merck KGaA, Darmstadt, Germany, and Pfizer to evaluate CMP-001, a TLR9 agonist, in combination with avelumab*, a human anti-PD-L1 antibody (Press release, Checkmate Pharmaceuticals, SEPT 5, 2018, View Source [SID1234529297]). The collaboration will evaluate the safety and effectiveness of CMP-001 administered in combination with avelumab in patients with advanced squamous cell cancer of the head and neck (SCCHN) resistant to a prior PD-1/PD-L1 inhibitor.

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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

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"This collaboration is an important next step in advancing our clinical development program for CMP-001 into indications beyond melanoma, where we already have demonstrated proof-of-concept,’’ said Art Krieg, CEO of Checkmate. "Merck KGaA, Darmstadt, Germany, and Pfizer are ideal partners for Checkmate given their commitment to developing avelumab broadly in the immuno-oncology field."

"Early data suggest CMP-001 exhibits clinically encouraging activity and we are looking forward to investigating this compound in combination with avelumab in advanced head and neck cancer," said Chris Boshoff, M.D., Ph.D., Senior Vice President and Head of Immuno-oncology, Early Development and Translational Oncology, Pfizer Global Product Development. "Our collaboration with Checkmate further demonstrates the alliance’s commitment to explore novel combinations with avelumab to potentially improve patient outcomes."

"Combining avelumab with CMP-001 adds to our clinical development strategy of IO combinations in different hard-to-treat cancers," said Alise Reicin, Head of Global Clinical Development at the Biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono. "We look forward to working with Checkmate to explore how the combination of these agents can potentially advance care for these patients."

Avelumab has received accelerated approval** by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and previously treated patients with locally advanced or metastatic urothelial carcinoma (mUC), and is under further clinical evaluation across a range of tumor types under a global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer.

*Avelumab is under clinical investigation for treatment of SCCHN in combination with CMP-001 and has not been demonstrated to be safe and effective for this use. There is no guarantee that avelumab will be approved for SCCHN by any health authority worldwide.

About CMP-001

CMP-001 is a first-in-class CpG-A Toll-like receptor 9 (TLR9) agonist that is encapsulated in a virus-like particle (VLP). CMP-001 is designed to induce both innate and adaptive anti-tumor immune responses, thereby converting immunologically "cold" tumors into immunologically "hot" tumors, with the potential to mediate tumor regression. It is the only CpG-A class TLR9 agonist in clinical trials and differs from other CpG classes in clinical development by having a native DNA backbone that induces the highest levels of type I IFN. Based on analyses of gene expression in human tumors showing that increased IFN and related immune gene expression is associated with better response to PD-1 inhibition, it is believed that this mechanism of action may restore, enable or improve responses to anti-PD-1/PD-L1 therapeutics.

CMP-001 is being evaluated in multiple tumor types to assess its safety, activity, alternative routes of administration and combination with other immunotherapies and modalities. For information on CMP-001 trials that are currently recruiting patients, please visit www.clinicaltrials.gov.

About Avelumab

Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.1-3 Avelumab has also been shown to induce NK cell mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.3-5 In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Avelumab is currently being evaluated in the JAVELIN clinical development program, which involves at least 30 clinical programs, including seven Phase III trials, and more than 8,600 patients across more than 15 different tumor types. For a comprehensive list of all avelumab trials, please visit clinicaltrials.gov.

Approved Indications in the US**

The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information from the US FDA Approved Label

The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO for mMCC and patients with locally advanced or metastatic UC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.

On September 5, 2018 Immunocore Limited, a leading T Cell Receptor (TCR) biotechnology company focused on delivering first-in-class biological therapies that have the potential to transform the lives of people with serious diseases, reported that it has received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for US Patent Application No. 13/319597 (Press release, Immunocore, SEP 5, 2018, View Source [SID1234529281]). The allowed claims cover the optimal format for TCR-based T cell redirectors and will provide broad protection for the Company’s novel ImmTAC platform. The grant of this U.S. patent will complete broad patent protection for the ImmTAC platform in the US and adds to equivalent patent protection already obtained in other major territories including Europe and China. ImmTAC molecules are the first T cell redirectors to have demonstrated a durable response and robust overall survival rate in patients with solid tumours.

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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

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Commenting on the announcement, Andrew Hotchkiss, Chief Executive Officer at Immunocore, said: "We are delighted that the USPTO has issued this Notice of Allowance, which will provide protection of our proprietary platform technology in the US until 2030. Together with other granted and pending patents, the Notice of Allowance cements the Company’s position as a leader in soluble TCR-based therapeutics."

Bent Jakobsen, Chief Scientific Officer at Immunocore and co-inventor of the technology, added: "The allowance of this patent application further exemplifies the Company’s world-leading science and innovation in the design of potent TCR-based biologics able to address some of the most difficult-to-treat tumours."

Immunocore’s extensive IP portfolio provides broad protection for the ImmTAC platform and serves to underpin the Company’s expanding pipeline of TCR-based biologics for the treatment of cancer and other serious diseases. The first ImmTAC to reach the clinic, IMCgp100 is in pivotal trials for the treatment of metastatic uveal melanoma, and a second ImmTAC molecule, IMCnyeso has recently commenced clinical testing for the treatment of various solid tumours.