On June 6, 2016 Kyowa Hakko Kirin Co., Ltd. (Tokyo; 4151 President and CEO: Nobuo Hanai; "Kyowa Hakko Kirin") reported the preliminary results today from the pivotal Phase 2 study of mogamulizumab (Code name: KW-0761) for the treatment of Adult T-cell Leukemia-Lymphoma (ATL) (Press release, Kyowa Hakko Kirin, JUN 5, 2016, View Source [SID:1234513141]).

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"We are very pleased to announce that we have completed the largest, prospective randomized clinical trial for relapsed/refractory ATL and that the preliminary results of this pivotal Phase 2 study showed potential of mogamulizumab for the treatment of relapsed/refractory ATL, where no standard of care exists" said Yoichi Sato, Managing Executive Officer, Vice President, Head of Research and Development Division of Kyowa Hakko Kirin.

Study Design
Patients from the USA, EU, and Latin America with aggressive relapsed or refractory ATL were randomized 2:1 to treatment with mogamulizumab or to 1 of 3 investigator choice (IC) regimens (Gem/Ox, DHAP or pralatrexate). Patients in the IC arm were permitted to cross-over to treatment with mogamulizumab after progression. Overall Response Rate (ORR; confirmed and unconfirmed) was assessed by the treating investigator (IA) and through blinded assessment by independent review (IR).

Study Results
71 patients were randomized (47 to mogamulizumab, 24 to IC). In the mogamulizumab treated group, unconfirmed ORR was 28% (13/47) by IR and 34% (16/47) by IA, while in the IC group, unconfirmed ORR was 8% (2/24) by IR and 0/24 by IA. Confirmed ORR (response maintained at successive evaluations approximately 8 weeks apart) for mogamulizumab was 11% by IR and 15% by IA, while there were no confirmed responses in the IC group. 18 out of 24 patients in the IC arm crossed over to mogamulizumab and 3 patients (17%) responded (1 of the responses was confirmed). The median duration of confirmed response for mogamulizumab was 5.0 months by IR and 5.5 months by IA. One patient had a response lasting more than 9 months. The frequently observed treatment-emergent, adverse events in the mogamulizumab arm included infusion reactions (46.8%), rash/drug eruption (19.1%) and infections (51.1%). The safety data collected from this study were similar to what has previously been documented.

These data from the study were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 5th, 2016.
The Kyowa Hakko Kirin Group companies strive to contribute to the health and well-being of people around the world by creating new value through the pursuit of advances in life sciences and technologies.

About Mogamulizumab
Mogamulizumab is a humanized mAb directed against CC chemokine receptor 4 (CCR4), which is frequently expressed on leukemic cells of certain hematologic malignancies including ATL. Mogamulizumab was produced using Kyowa Hakko Kirin’s proprietary POTELLIGENT platform, which is associated with enhanced antibody-dependent cellular cytotoxicity (ADCC), and was launched in Japan in May 2012 for the treatment of patients with relapsed or refractory CCR4-positive ATL under the trade name POTELIGEO. The drug was approved for indication expansion and was granted marketing authorization in Japan for the treatment of patients with relapsed or refractory CCR4-positive, peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) in March 2014, and with chemotherapy-naive CCR4-positive ATL in December 2014.

About Adult T-cell Leukemia-Lymphoma (ATL)
ATL is a disease entity within the category of mature T- and NK-cell neoplasms, according to the classification by the World Health Organization. It is an extremely aggressive T lymphocytic malignancy that originates in T-cells infected with the human T-lymphotropic virus-1(HTLV-1). ATL has a very distinct epidemiology and geographic distribution, primarily involving areas of Japan, the Caribbean Basin, parts of South America, the Middle East and sub-Saharan Africa, where HTLV-1 infection is endemic. In non-endemic regions such as North America and Europe, HTLV-1 infection is mainly found in immigrants from endemic areas, their offspring or sexual contacts. Treatment regimens for ATL have not been standardized, especially in the relapsed/refractory setting, representing a large unmet medical need in this patient population.

On June 5, 2016 Exelixis, Inc. (NASDAQ:EXEL) and Ipsen (Euronext:IPN; ADR:IPSEY) reported overall survival (OS) results from the phase 3 METEOR trial of CABOMETYX (cabozantinib) tablets in patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy (Press release, Exelixis, JUN 5, 2016, View Source;p=RssLanding&cat=news&id=2175112 [SID:1234513004]). The findings will be presented during an oral abstract session today at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, and were published today in The Lancet Oncology.1 The OS results demonstrate that CABOMETYX reduces the risk of death by one third versus everolimus.

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Exelixis previously announced that METEOR met its primary endpoint, progression-free survival (PFS), and secondary endpoints, OS and objective response rate.

"The overall survival benefit conferred by treatment with CABOMETYX — which was consistently favorable across a variety of prespecified and post-hoc patient subgroups — is a strong complement to the progression-free survival and objective response rate findings previously reported," said Toni Choueiri, M.D., Clinical Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute. "With the recent FDA approval of CABOMETYX, patients in need of additional options now have access to a differentiated treatment demonstrated to help them live longer while also delaying the progression of their cancer."

In METEOR, at a median follow-up of nearly 19 months, CABOMETYX demonstrated an increase in median OS of nearly 5 months versus everolimus: 21.4 months versus 16.5 months for everolimus (HR 0.66, 95% CI [0.53-0.83], P=0.0003), corresponding to a 34 percent reduction in the risk of death.

CABOMETYX treatment resulted in consistent benefits in OS and PFS across various pre-specified and post-hoc analysis subgroups. Benefits were independent of Memorial Sloan Kettering Cancer Center risk group (favorable, intermediate, or poor), number and type of prior vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapies (one, or more than one), duration of first VEGFR TKI treatment (6 months or less, or more than 6 months), presence of bone and/or visceral metastases, and levels of the MET biomarker in tumors (high, low, or unknown). Additional details on benefits seen in subgroups of patients based on the presence of bone metastases and prior VEGFR TKI therapy will be presented in a poster session at 1 p.m. CDT on June 6.

"We are excited to share the detailed overall survival results from the METEOR trial with the oncology community at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting," said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. "The five-year survival rate for patients diagnosed with advanced kidney cancer is only 12 percent, underscoring the need for new treatment options that help patients live longer while delaying the progression of their disease. Critically, CABOMETYX — the first FDA-approved therapy to demonstrate a benefit in all three key efficacy parameters — now shows consistent survival benefit across all subgroups of patients evaluated in METEOR."

"Recent data from the METEOR trial confirms the benefit in median overall survival of almost 5 months that CABOMETYX can provide to patients with advanced renal cell carcinoma," said Marc de Garidel, Chairman and CEO, Ipsen. "We are dedicated to diligently working with Exelixis and regulatory authorities to bring cabozantinib to patients who seek new therapeutic options with established survival benefits."

At the time of the analysis, the median duration of treatment in the trial was 8.3 months with CABOMETYX versus 4.4 months with everolimus. Dose reductions occurred for 62 percent and 25 percent of patients, respectively. Discontinuation rate due to an adverse event not related to disease progression was 12 percent with CABOMETYX and 11 percent with everolimus.

The most common grade 3 or 4 adverse events were hypertension (15 percent), diarrhea (13 percent) and fatigue (11 percent) in the CABOMETYX arm and anemia (17 percent), fatigue (7 percent) and hyperglycemia (5 percent) in the everolimus arm. Serious adverse events ≥ grade 3 occurred in 130 (39 percent) of cabozantinib-treated patients and in 129 (40 percent) of everolimus-treated patients.

On April 25, 2016 CABOMETYX was approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy.

Please see Important Safety Information below and full U.S. prescribing information for CABOMETYX (cabozantinib) tablets at View Source

About the METEOR Phase 3 Pivotal Trial

METEOR was an open-label, event-driven trial of 658 patients with advanced renal cell carcinoma who had failed at least one prior VEGFR TKI therapy. The primary endpoint was PFS in the first 375 patients treated. Secondary endpoints included OS and objective response rate in all enrolled subjects. The trial was conducted at approximately 200 sites in 26 countries, and enrollment was weighted toward Western Europe, North America, and Australia.

Patients were randomized 1:1 to receive 60 mg of CABOMETYX daily or 10 mg of everolimus daily and were stratified based on the number of prior VEGFR TKI therapies received and on MSKCC risk criteria. No cross-over was allowed between the study arms.

METEOR met its primary endpoint of significantly improving PFS. Compared with everolimus, CABOMETYX was associated with a 42 percent reduction in the rate of disease progression or death. Median PFS for CABOMETYX was 7.4 months versus 3.8 months for everolimus (HR=0.58, 95% CI 0.45-0.74, P<0.0001). CABOMETYX also significantly improved the objective response rate compared with everolimus (P<0.0001). These data were presented at the European Cancer Congress in September 2015 and published in The New England Journal of Medicine.2

Exelixis to Host Investor/Analyst Briefing Later Today

Exelixis will host a live investor/analyst briefing today, Sunday, June 5, 2016, from 7:30-9:30 p.m. EDT / 6:30-8:30 p.m. CDT / 4:30-6:30 p.m. PDT. During the briefing, Exelixis management and invited guest speakers will review and provide context for the cabozantinib data presented at the ASCO (Free ASCO Whitepaper) Annual Meeting. The briefing will be webcast live and can be accessed by logging on to www.exelixis.com and proceeding to the Event Calendar page under Investors & Media. Please connect to the company’s website at least 15 minutes prior to the webcast to ensure adequate time for any software download that may be required to listen to the webcast. An archived replay of the webcast will also be available on the Event Calendar page under Investors & Media at www.exelixis.com for one year. A telephone replay of the webcast will be available until 11:59 p.m. EDT on June 7, 2016. Access numbers for the phone replay are: 855-859-2056 (domestic) and 404-537-3406 (international); the passcode is 15007787.

About Advanced Renal Cell Carcinoma

The American Cancer Society’s 2016 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.3 Clear cell RCC is the most common type of kidney cancer in adults.4 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12 percent, with no identified cure for the disease.3 Approximately 17,000 patients in the U.S. and 37,000 globally require second-line or later treatment.5

The majority of clear cell RCC tumors have lower than normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.6,7 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.8-11 MET and AXL may provide escape pathways that drive resistance to VEGFR inhibitors.7,8

About CABOMETYX

CABOMETYX targets include MET, AXL and VEGFR-1, -2 and -3. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.

CABOMETYX, the tablet formulation of cabozantinib, is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.

On April 25, 2016, the FDA approved CABOMETYX tablets for the treatment of patients with advanced renal cell carcinoma who have received prior anti-angiogenic therapy.

On January 28, 2016, the European Medicines Agency (EMA) validated Exelixis’ Marketing Authorization Application (MAA) for cabozantinib as a treatment for patients with advanced renal cell carcinoma who have received one prior therapy. The MAA has been granted accelerated assessment, making it eligible for a 150-day review, versus the standard 210 days. On February 29, 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan.

Important Safety Information

Hemorrhage: Severe hemorrhage occurred with CABOMETYX. The incidence of Grade ≥3 hemorrhagic events was 2.1% in CABOMETYX-treated patients and 1.6% in everolimus-treated patients. Fatal hemorrhages also occurred in the cabozantinib clinical program. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.

Gastrointestinal (GI) Perforations and Fistulas: Fistulas were reported in 1.2% (including 0.6% anal fistula) of CABOMETYX-treated patients and 0% of everolimus-treated patients. GI perforations were reported in 0.9% of CABOMETYX-treated patients and 0.6% of everolimus-treated patients. Fatal perforations occurred in the cabozantinib clinical program. Monitor patients for symptoms of fistulas and perforations. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.

Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. Venous thromboembolism was reported in 7.3% of CABOMETYX-treated patients and 2.5% of everolimus-treated patients. Pulmonary embolism occurred in 3.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Events of arterial thromboembolism were reported in 0.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.

Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension. Hypertension was reported in 37% (15% Grade ≥3) of CABOMETYX-treated patients and 7.1% (3.1% Grade ≥3) of everolimus-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.

Diarrhea: Diarrhea occurred in 74% of patients treated with CABOMETYX and in 28% of patients treated with everolimus. Grade 3 diarrhea occurred in 11% of CABOMETYX-treated patients and in 2% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to diarrhea occurred in 26% of patients.

Palmar-Plantar Erythrodysesthesia Syndrome (PPES): Palmar-plantar erythrodysesthesia syndrome (PPES) occurred in 42% of patients treated with CABOMETYX and in 6% of patients treated with everolimus. Grade 3 PPES occurred in 8.2% of CABOMETYX-treated patients and in <1% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPES or Grade 3 PPES until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to PPES occurred in 16% of patients.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Embryo-fetal Toxicity: CABOMETYX can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.

Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, PPES, hypertension, vomiting, weight decreased, and constipation.

Drug Interactions: Strong CYP3A4 inhibitors and inducers: Reduce the dosage of CABOMETYX if concomitant use with strong CYP3A4 inhibitors cannot be avoided. Increase the dosage of CABOMETYX if concomitant use with strong CYP3A4 inducers cannot be avoided.

Lactation: Advise a lactating woman not to breastfeed during treatment with CABOMETYX and for 4 months after the final dose.

Reproductive Potential: Contraception―Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the final dose. Infertility ―CABOMETYX may impair fertility in females and males of reproductive potential.

Hepatic Impairment: Reduce the CABOMETYX dose in patients with mild (Child-Pugh score [C-P] A) or moderate (C-P B) hepatic impairment. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

Please see full Prescribing Information at View Source

On June 5, 2016 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported that interim results from the Phase 1 clinical trial of RXDX-105, the company’s orally available, small molecule multikinase inhibitor with potent activity against such targets as RET and BRAF, were presented at the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago (Abstract 2574) (Press release, Ignyta, JUN 5, 2016, View Source [SID:1234513070]). RXDX-105 is Ignyta’s second clinical stage compound after entrectinib, the furthest advanced inhibitor for solid tumors with NTRK (neurotrophin receptor kinase), ROS1, or ALK gene rearrangements.

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"We continue to be encouraged by the safety and preliminary antitumor activity data from our Phase 1 clinical trial of RXDX-105," said Pratik Multani, M.D., Chief Medical Officer of Ignyta. "Given the performance of RXDX-105 thus far, we look forward to the results from the Phase 1b portion of the study, in which we are further evaluating this investigational agent and its activity in targeted patient populations with relevant molecular alterations, as well as in patients with unselected lung cancer."

The Phase 1 dose escalation portion of the clinical trial was designed to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), as well as preliminary anti-cancer activity, of single agent RXDX-105 in patients with advanced or metastatic solid tumors.

As of the May 3, 2016, data cut-off, the findings showed:

A total of 55 patients with a range of solid tumors were dosed with RXDX-105 in the clinical trial;
RXDX-105 was well tolerated:
The most frequent treatment-emergent adverse events were fatigue, nausea, rash, vomiting, diarrhea, decreased appetite, constipation, anemia, muscle spasms, and abdominal pain;
Four Grade 3 dose-limiting toxicities (DLTs) were observed: maculopapular rash, fatigue, diarrhea and hyperbilirubinemia, each of which resolved upon study drug interruption; and
Three serious adverse events (SAEs) were considered treatment-related: Grade 2 headache, Grade 3 hyperbilirubinemia and Grade 3 drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). No Grade 4 or Grade 5 treatment-related adverse events were observed;
An MTD based on DLTs was not reached; based upon overall safety and exposure during Phase 1, the RP2D was determined to be 350 mg, once daily in the fed state, and is being further evaluated in the Phase 1b portion of the study;
Pharmacokinetic measurements showed increased exposure with increasing dose, with a half-life compatible with once-daily dosing. Dosing in the fed state appears to increase exposure over dosing in the non-fed state;
Exposures reached levels expected to be efficacious based on tumor growth inhibition in animal models of RET- and BRAF-driven tumors; and
Twenty patients were dosed at or above the clinically relevant dose of 275 mg in the fed state, 11 of whom had an actionable RET or BRAF alteration. Tumor regression of greater than 20% was observed in four of the 20 patients, including:
an unconfirmed partial response (38% reduction) in a patient with medullary thyroid cancer with a RET M918T mutation;
a 28% reduction in target lesions in a patient with non-small cell lung cancer (NSCLC) with a BRAF D594G mutation;
a 26% reduction in target lesions in a patient with ovarian cancer with a BRAF V600E mutation; and
finally, as previously reported at the ENA Conference 2015 (Wang, 2015), a confirmed partial response (40% reduction) in a patient with NSCLC with a KRAS G12C mutation, who continues on treatment after 10 cycles.
In addition to RXDX-105, Ignyta is developing a pipeline of first-in-class and best-in-class molecularly targeted therapies to fight cancer – with the ultimate goal of not just shrinking tumors, but eradicating cancer relapse and recurrence in precisely defined patient populations. Ignyta recently presented combined data from two Phase 1 clinical trials of its lead product candidate entrectinib that indicated the drug showed signs of clinical activity in patients who had several different types of cancer with NTRK1/2/3, ROS1 or ALK gene alterations and had not previously been treated with a Trk-, ROS1-, or ALK-directed targeted therapy. Entrectinib is the most potent Trk inhibitor in the clinic and the only Trk inhibitor with clinically demonstrated activity against primary and metastatic tumors in the central nervous system (CNS), a frequent site of progression of advanced solid tumors.

"We are excited to continue testing the potential for our molecularly targeted therapies, like entrectinib and RXDX-105, to shrink tumors and eradicate residual disease in selected patient populations," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "We remain committed to serving those patients who have the highest unmet need and may otherwise not have effective treatment options."

On Monday, June 6, 2016, Ignyta will file a Form-8-K with the U.S. Securities and Exchange Commission (SEC) containing the materials presented at the ASCO (Free ASCO Whitepaper) Annual Meeting. The company’s SEC filings can be found on the company’s website at www.ignyta.com and on the SEC’s website at www.sec.gov.

On June 5, 2016 Tyrogenex, a privately held biopharmaceutical company, reported that data from its Phase I study of X-82, an oral dual anti-VEGFR/PDGFR tyrosine kinase inhibitor, with everolimus in solid tumors were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2016 held in Chicago, Illinois (Press release, Tyrogenex, JUN 5, 2016, View Source [SID:1234513093]).

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The data presented were from the Phase I study in which X-82 was combined with full dose everolimus in solid tumors to determine the dose limiting toxicities and recommended Phase II dose for pNET and RCC. Results were presented by Dr. Benjamin R. Tan, MD, Washington University School of Medicine, in a poster titled "Phase I study of X-82, an oral dual anti-VEGFR/PDGFR tyrosine kinase inhibitor, with everolimus in solid tumors."

"The results from this study provide critical information for moving forward with the development of X-82 in solid tumors," said Dr. Tan. "We have also seen favorable responses in renal cell carcinoma (RCC) and prolonged stable diseases (SD) in neuroendocrine tumors (NET) patients, which warrant further investigations in these tumor types. Tyrogenex continued to advances this program with the goal of providing patients suffering from a variety of solid tumors with a safe and effective treatment option."

About the Phase I Study

A 3+3 dose escalation design was utilized to determine the dose limiting toxicities and the recommended Phase II dose of daily oral X-82 plus everolimus at 10 mg PO daily for patients with solid malignancies. Key eligibility criteria included PS 0-1, measurable disease adequate organ function and normal LVEF.

Key conclusions from the study include:

Recommended Phase II dose is X-82 at 300 mg PO daily plus everolimus at 10 mg PO daily
Dose limiting toxicities include Grade 3 fatigue, mucositis and hypophosphatemia
Encouraging responses and prolonged stable disease seen in RCC and NETs
An expansion cohort for RCC and PNET are ongoing at Washington University and Vanderbilt University
About X-82

Tyrogenex’s lead compound is X-82. X-82 inhibits both VEGF and PDGFR. Tyrogenex believes X-82 targets the basic mechanisms of neovascular eye diseases, including angiogenesis, fibrosis and inflammation. X-82 is currently being evaluated for wet Age-Related Macular Degeneration (AMD) and solid tumors.

On June 5, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) and it collaborators reported data showing that higher tumor mutational burden, as estimated by comprehensive genomic profiling with FoundationOne, successfully predicted a greater likelihood of response and longer response duration to cancer immunotherapies in patients with advanced bladder cancer and metastatic melanoma as well as several other tumor types (Press release, Foundation Medicine, JUN 5, 2016, View Source [SID:1234513005]). The results were presented in two oral sessions, and several poster discussions at the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) taking place in Chicago.

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"Successful application of cancer immunotherapy in the clinic is one of the most important advances in cancer treatment in decades," said Vincent Miller, M.D., chief medical officer at Foundation Medicine. "These data suggest that tumor mutational burden could serve as an independent predictive biomarker to aid clinicians in identifying patients who are most likely to benefit from cancer immunotherapies that target either the PD-1 or PD-L1 proteins."

Cancer immunotherapy works by helping the immune system mount an effective anti-cancer response, a process that depends in part on the recognition of cancer-specific proteins called neoantigens. Tumor mutational burden has been shown to correlate well with the number of neoantigens, and therefore it may help identify patients most likely to respond to cancer immunotherapies. By combining comprehensive genomic profiling of 315 genes utilizing the FoundationOne assay, with Foundation Medicine’s advanced and proprietary algorithm that filters out normal individual genomic variants, FoundationOne can reliably and accurately measure tumor mutational burden without the need for whole exome sequencing. Foundation Medicine expects to provide a CLIA-certified version of tumor mutational burden on all FoundationOne and FoundationOne Heme reports to physicians in the third quarter 2016.

Overview of Data Presentations

The IMvigor 210 study of TecentriqTM (atezolizumab; anti-PD-L1; Genentech/Roche) in locally advanced or metastatic urothelial carcinoma evaluated three separate biomarkers: PD-L1 protein expression as measured by immunohistochemistry, molecular subtype as measured by gene expression and The Cancer Genome Atlas, and mutational load (often referred to as tumor mutational burden) as measured by FoundationOne. All three biomarkers were shown to be independent predictors of response to Tecentriq.

"PD-L1 Expression, Cancer Genome Atlas (TCGA) Subtype and Mutational Load are Independent Predictors of Response to Atezolizumab (atezo) in Metastatic Urothelial Carcinoma (mUC; Imvigor210)", by Jonathan E. Rosenberg, M.D., Memorial Sloan Kettering Cancer Center [Abstract #104, Clinical Science Symposium, Sunday June 5, 9:57-10:09 AM].
"These results are particularly exciting given the amount of variability inherent to using immunohistochemistry (IHC) to measure biomarkers. There are many different PD-L1 IHC tests, for example, and pathologists often do not see agreement between them," stated Vamsidhar Velcheti, M.D., assistant professor, Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic. "We need a truly quantitative and reproducible approach to predicting response to immunotherapies, and measuring tumor mutational burden using FoundationOne may provide us with that solution."

In a separate melanoma study, higher mutational burden as measured by FoundationOne was associated with a greater likelihood of response and a more durable response to pembrolizumab; anti-PD-1; Merck, nivolumab; anti-PD-1; Bristol Myers Squibb, and Tecentriq, thereby providing oncologists with greater confidence in the potential for clinical benefit from a host of newly approved immunotherapies.

"Hybrid Capture-Based Next Generation Sequencing (HC NGS) in Melanoma Identifies Markers of Response to Anti-PD1/PD-L1", by Douglas Buckner Johnson, M.D., M.S.C.I., Vanderbilt-Ingram Cancer Center [Abstract #105, Clinical Science Symposium, Sunday June 5, 10:21-10:33 AM]
Dr. Miller continued, "The clinical reality is that some patients respond very well to cancer immunotherapies and others do not. As a result, the ability to leverage our molecular information platform to identify the right candidates for these immunotherapies is an important advance for the field of precision medicine. Matching the right therapy with the right patient has the potential to both improve outcomes and increase efficiency in the current care model."

These conclusions were further supported by two additional presentations at ASCO (Free ASCO Whitepaper) 2016 that demonstrated that total mutational burden could also predict response to cancer immunotherapy in lung and colorectal cancers:

"Total Mutational Burden (TMB) in Lung Cancer and Relationship with Response to PD-1/PD-L1 Targeted Therapies", by David R. Spigel, M.D., Sarah Cannon Research Institute [Abstract #9017, Poster Session, Saturday June 4, 8:00-11:30 AM].
"Tumor Mutational Burden as a Potential Biomarker for PD1/PD-L1 Therapy in Colorectal Cancer", by Thomas J. George, M.D., F.A.C.P., University of Florida [Abstract #3587, Poster Session, Saturday June 4, 8:00-11:30 AM].