On January 9, 2017 Incyte Corporation (Nasdaq:INCY) and Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported the decision to advance the clinical development program investigating the combination of epacadostat, Incyte’s investigational oral selective IDO1 inhibitor, with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy (Press release, Incyte, JAN 9, 2017, View Source [SID1234517316]).

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With the expansion of the clinical development program, the companies plan to initiate pivotal studies of epacadostat in combination with KEYTRUDA in four additional tumors: non-small cell lung cancer, renal cell carcinoma, bladder cancer and squamous cell carcinoma of the head and neck. Presentations of data from the ongoing studies of epacadostat in combination with KEYTRUDA, which support this decision, are expected at upcoming medical meetings.

"We are very pleased to announce the decision with Merck to initiate additional Phase 3 studies that will further evaluate the clinical utility of epacadostat in combination with KEYTRUDA," said Steven Stein, M.D., Incyte’s Chief Medical Officer. "Data from across the ECHO development program for epacadostat continues to be accrued, including from the ECHO-202 Phase 2 cohorts in combination with KEYTRUDA which support the decision to move forward into pivotal studies beyond melanoma. We look forward to initiation of these new Phase 3 trials as we seek to help improve clinical outcomes for patients with these cancers."

"The expansion of our clinical trial program with Incyte is an important component of our comprehensive approach to investigating the potential for KEYTRUDA in combination with promising compounds, such as epacadostat, to help make a difference in the lives of people with these cancers," said Dr. Roy Baynes, senior vice president, head of clinical development, and Chief Medical Officer, Merck Research Laboratories.

About ECHO
The ECHO clinical trial program was established to investigate the efficacy and safety of epacadostat as a core component of combination therapy in oncology. Ongoing Phase 1 and Phase 2 studies evaluating epacadostat in combination with PD-1 and PD-L1 inhibitors collectively plan to enroll over 900 patients in a broad range of solid tumor types as well as hematological malignancies. ECHO-301 (NCT02752074), a Phase 3 randomized, double-blind, placebo-controlled study investigating pembrolizumab in combination with epacadostat or placebo for the first-line treatment of patients with advanced or metastatic melanoma, is also underway. ECHO-301 was initiated in June 2016 and initial data from this study are expected to be available in 2018.

About Epacadostat (INCB024360)
Indoleamine 2,3-dioxygenase 1 (IDO1) is a key immunosuppressive enzyme that modulates the anti-tumor immune response by promoting regulatory T cell generation and blocking effector T cell activation, thereby facilitating tumor growth by allowing cancer cells to avoid immune surveillance. Epacadostat is a first-in-class, highly potent and selective oral inhibitor of the IDO1 enzyme that reverses tumor-associated immune suppression and restores effective anti-tumor immune responses. In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma. In these studies, epacadostat combined with the CTLA-4 inhibitor ipilimumab or the PD-1 inhibitor pembrolizumab improved response rates compared with studies of the immune checkpoint inhibitors alone.

About KEYTRUDA (pembrolizumab)
KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.
KEYTRUDA Indications and Dosing
Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.
Lung Cancer

KEYTRUDA is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA (pembrolizumab) is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA (pembrolizumab) for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and betablockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.
KEYTRUDA can cause other clinically important immune-mediated adverse reactions. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma.

KEYTRUDA (pembrolizumab) can cause severe or life-threatening infusion-related reactions, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

In KEYNOTE-002, KEYTRUDA was discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). Adverse reactions leading to interruption of KEYTRUDA occurred in 14% of patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%), and maculopapular rash (1%). The most common adverse reactions with KEYTRUDA vs chemotherapy were fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs 20%), and decreased appetite (20% with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.
KEYTRUDA was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

KEYTRUDA (pembrolizumab) was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of patients) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.
Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

On January 9, 2017 Cellular Biomedicine Group Inc. (CBMG) ("CBMG" or the "Company"), a clinical-stage biomedicine firm engaged in the development of effective immunotherapies for cancer and stem cell therapies for degenerative diseases, reported the approval and commencement of patient enrollment in China for its CALL-1 ("CAR-T against Acute Lymphoblastic Leukemia") Phase I clinical trial utilizing its optimized proprietary C-CAR011 construct of CD19 chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of patients with relapsed or refractory (r/r) CD19+ B-cell Acute Lymphoblastic Leukemia (ALL) (Press release, Cellular Biomedicine Group, JAN 9, 2017, View Source [SID1234517313]). The CALL-1 trial has begun enrollment with final data expected to be available at the end of 2017. Depending on the Phase I CALL-1 results, CBMG expects to initiate a larger Phase II clinical trial as soon as practicable.

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"Our CALL-1 trial represents the second CBMG-sponsored clinical trial after the recent launch of our CARD-1 trial in refractory DLBCL patients. This is another major corporate milestone and demonstrates CBMG’s ability to execute on our immuno-oncology plan and to forward our prioritized assets into clinical development in China," said Tony (Bizuo) Liu, Chief Executive Officer of CBMG.

CBMG’s CALL-1 Phase I dose-escalation trial will use the 3+3 design to evaluate the safety, efficacy and persistence of C-CAR011 in CD19+ r/r ALL patients.

"Relapsed or refractory CD19+ adult ALL patients have limited options and poor prognosis," said Dr. Li Yu from the PLA General Hospital ("PLAGH"), the Principal Investigator for the CALL-1 trial. "I am excited to be able to participate in the trial of C-CAR011 which may someday provide a treatment option for these patients."

"We are excited to launch this trial to better understand the potential C-CAR011 can have to address a large cancer population in China," said Dr. Yihong Yao, Chief Scientific Officer of CBMG.

About the CALL-1 Clinical Trial
CALL-1 is a Phase I single-site, single-arm dose-escalating trial consisting of three patient cohorts using escalating C-CAR011 cell dosing levels with three patients in each cohort. Phase I dose expansion will enroll an additional 6-12 patients to confirm the optimal dose. The primary end points are Dose-Limiting Toxicity (DLT) and Treatment Emergent Adverse Events (TEAE). Secondary endpoints will measure Overall Response Rate (CR + CRi, complete remission with incomplete hematopoietic recovery), MRD-CR rate at 8 weeks according to the NCCN Guideline Version 2.2016, Acute Lymphoblastic Leukemia, and overall survival at 6 months.

Dr. Li Yu, Director emeritus, Professor and Chief Physician of the Department of Hematology at the PLAGH in Beijing, China will conduct the trial. The PLAGH was founded in 1953 and is a top-ranking medical center in China, integrating medical care, education and research. The PLAGH has 125 clinical, medical and technological departments, 4,000 patient beds with annual volumes of more than 3.8 million outpatient visits, 110,000 admissions and over 65,000 surgical operations performed.

About C-CAR011
CBMG’s proprietary anti-CD19 chimeric antigen receptor T-cell (CAR-T) construct represents advancement over CBMG’s prior CBM-C19.1 construct, which completed a human proof-of-concept trial demonstrating an optimistic response rate with controllable toxicities. C-CAR011 is entirely engineered and manufactured in CBMG’s own GMP manufacturing facility in China.

About Acute Lymphoblastic Leukemia (ALL)
Acute Lymphoblastic Leukemia (ALL), also called acute lymphocytic leukemia, starts from the early type of white blood cells called lymphocytes in the bone marrow. The leukemia cells then invade the blood fairly quickly and may spread to other parts of the body, including the lymph nodes, liver, spleen, central nervous system (brain and spinal cord), and testicles (in males). The World Health Organization defines "acute" when greater than 20% of the cells in the bone marrow are blasts, which can progress quickly, and if untreated, would likely be fatal within months. According to the U.S. National Cancer Institute, 6,600 patients are diagnosed with ALL in the U.S. annually. Additionally, it is estimated that 27,000 patients in China will be diagnosed with ALL annually. While pediatric patients make up approximately 60% of the total and achieve an 85% effective cure rate, only 40% of Adult ALL patients achieve long-term disease-free survival.

On January 9, 2017 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that, per the licensing agreement for lirilumab, Bristol-Myers Squibb has paid Innate Pharma a US$15 million milestone payment for the continued exploration of lirilumab in combination with Opdivo (nivolumab) (Press release, Innate Pharma, JAN 9, 2017, View Source [SID1234517308]).

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This milestone payment follows the presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting (November 2016) of encouraging preliminary activity results from the cohort of patients with Squamous Cell Cancer of the Head and Neck (SCCHN) of a Phase I/II trial. These interim efficacy results – the first report for the combination of an anti-KIR antibody and an anti-PD-1 therapy – indicate that targeting both pathways with lirilumab and nivolumab respectively may provide enhanced clinical activity, particularly in PD-L1 positive tumors, with deep and durable responses in some patients.

Pierre Dodion, Chief Medical Officer at Innate Pharma, said: "The combination of lirilumab with nivolumab showed encouraging early efficacy signals in the initial part of the trial which support the strategy of simultaneously targeting the KIR and PD-1 pathways with lirilumab and nivolumab, respectively; the reported data point to broader potential for lirilumab. We look forward to further investigation of the combination in the Phase II part of this trial."

In total, Bristol-Myers Squibb is currently investigating lirilumab in six trials, across a range of solid and hematological cancer indications, in monotherapy and in combination with other agents, and Innate Pharma is responsible for conducting the EffiKIR trial, a randomized Phase II trial evaluating lirilumab as a single agent in patients with acute myeloid leukemia (see on clinicaltrials.gov).

About CA223-001: A Phase I/II Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of Anti-KIR (Lirilumab) Administered in Combination With Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors
CA223-001 is a Phase I/II dose escalation and cohort expansion study of lirilumab in combination with nivolumab in patients with advanced solid tumors.
During the dose escalation, patients with advanced solid tumors who progressed after ≥ 1 prior therapy received lirilumab 0.1–3.0 mg/kg once every 4 weeks (Q4W) plus nivolumab 3.0 mg/kg Q2W. Cohort expansion was initiated at the maximum dose of lirilumab 3.0 mg/kg Q4W plus nivolumab 3.0 mg/kg Q2W in patients with advanced solid tumors. The data reported at SITC (Free SITC Whitepaper) pertain to an expansion cohort in SCCHN. Key study endpoints include safety (primary), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and biomarker assessments.

The purpose of this Phase I/II open label study is to determine the safety of the combination of lirilumab and nivolumab and to explore the preliminary anti-tumor activity of the combination in patients with a range of advanced solid tumors.

On January 9, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for TECENTRIQ (atezolizumab) for the treatment of people with locally advanced or metastatic urothelial carcinoma (mUC) who are ineligible for cisplatin chemotherapy, and are either previously untreated (first-line) or have disease progression at least 12 months after receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant) (Press release, Hoffmann-La Roche, JAN 9, 2017, View Source [SID1234517307]). Urothelial carcinoma accounts for 90 percent of all bladder cancers and can also be found in the renal pelvis, ureter and urethra.

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"In May 2016, TECENTRIQ became the first treatment approved by the FDA for people with previously treated advanced bladder cancer in more than 30 years," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "We are committed to continue working with the FDA to make TECENTRIQ available to more people with this type of advanced bladder cancer, specifically those who are unable to tolerate cisplatin-based chemotherapy as an initial treatment."

This sBLA submission for TECENTRIQ is based on results from the Phase II IMvigor210 study, and the FDA will make a decision on approval by 30 April 2017. A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention or diagnosis of a serious disease.
TECENTRIQ is currently approved by the FDA to treat people with locally advanced or mUC who have disease progression during or following platinum-based chemotherapy or whose disease has worsened within 12 months of neoadjuvant or adjuvant platinum-based chemotherapy. TECENTRIQ is approved under accelerated approval for this indication based on tumour response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. TECENTRIQ is also approved for the treatment of people with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumour has EGFR or ALK gene abnormalities.

About the IMvigor210 study
IMvigor210 is an open-label, multicenter, single-arm Phase II study that evaluated the safety and efficacy of TECENTRIQ in people with locally advanced or mUC, regardless of PD-L1 expression. People in the study were enrolled into one of two cohorts. Cohort 1, upon which this sBLA submission is based, consisted of people who were ineligible for first-line cisplatin-based chemotherapy, and who had received no prior chemotherapies for locally advanced or mUC (i.e., first-line) or had disease progression at least 12 months after neoadjuvant or adjuvant chemotherapy. Cohort 2, which served as the basis for the FDA’s accelerated approval of TECENTRIQ in May 2016, included people whose disease had progressed during or following previous treatment with a platinum-based chemotherapy regimen, or who had disease progression within 12 months of treatment with a platinum-based neoadjuvant or adjuvant chemotherapy regimen. The primary endpoint of the study was objective response rate (ORR). Secondary endpoints included duration of response (DOR), overall survival (OS), progression-free survival (PFS) and safety.

About metastatic urothelial carcinoma
Metastatic urothelial cancer (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. 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 target and bind to a protein called PD-L1 (programmed death-ligand 1), which is expressed on tumour cells and tumour-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, TECENTRIQ may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells. TECENTRIQ is currently only approved in the US.

On January 9, 2017 Amgen (NASDAQ:AMGN) and Immatics Biotechnologies GmbH, a leading company in the field of cancer immunotherapy, reported a research collaboration and exclusive license agreement to develop next-generation, T-cell engaging bispecific immunotherapies targeting multiple cancers (Press release, Amgen, JAN 9, 2017, View Source [SID1234517306]).

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The collaboration will combine Immatics’ world-leading XPRESIDENT target discovery and T-cell receptor (TCR) capabilities with Amgen’s validated Bispecific T-cell Engager (BiTE) technology with the aim of creating novel oncology drugs. Amgen will be responsible for the clinical development, manufacturing and commercialization worldwide.

Under the terms of the agreement, Immatics will receive an upfront fee of $30 million and is eligible to receive over $500 million in development, regulatory and commercial milestone payments for each program and tiered royalties up to a double-digit percentage of net sales.

"We are very pleased to be entering this strategic collaboration with Amgen, which is contributing its bispecific T-cell engagers expertise, as together we look to develop novel immunotherapies that will deliver a step change in the treatment of several cancers. This collaboration also demonstrates Amgen’s confidence in Immatics’ world-leading immune-oncology target and TCR discovery capabilities," said Carsten Reinhardt, M.D., Ph.D., managing director and chief medical officer at Immatics.

"The intersection of immunology and oncology represents a promising and rapidly developing approach that can have a significant impact for patients with cancer," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We look forward to collaborating with Immatics to translate their unique target and TCR discovery capabilities combined with Amgen’s validated BiTE technology into novel therapies."

About T-cell Engaging Bispecific Cancer Immunotherapies

T-cell engaging bispecifics leverage the body’s immune system by redirecting the T-cell response towards cancer cells expressing specific tumor antigens. Immatics’ TCR-bispecifics and Amgen’s BiTE antibody constructs each possess two or more binding domains. One such binding domain specific to an intracellular antigen discovered by XPRESIDENT presented on the surface of a cancer cell; another such binding domain is designed to recognize a T-cell activator, such as CD3. This approach allows every T-cell to become activated and able to attack the tumor, independent of the T-cells’ intrinsic specificity. This bispecific approach is designed to improve the immunotherapies’ ability to eradicate malignant cells while avoiding damage to healthy tissues.