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ImmunoGen Reports Recent Progress and Operating Results for Six-Month Period and Quarter Ended December 31, 2016

On February 17, 2016 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported recent highlights and reported financial results for the six-month period and quarter ended December 31, 2016 (Press release, ImmunoGen, FEB 17, 2017, View Source [SID1234517759]).

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"In 2016, we strengthened ImmunoGen operationally and financially with a focused strategy and disciplined execution," said Mark Enyedy, ImmunoGen’s president and chief executive officer. "Building upon this momentum, we enter 2017 well positioned to deliver on multiple clinical milestones. In January, we advanced our lead program to Phase 3, dosing the first patient in the FORWARD I study of mirvetuximab soravtansine in ovarian cancer. At the Society of Gynecologic Oncology annual meeting next month, we will present data from the mirvetuximab biopsy cohort, followed by initial data in the second quarter from the mirvetuximab combination regimens being evaluated in our FORWARD II study. We are also excited about the potential of our DNA-alkylating ADCs and expect to report the first data from the Phase 1 study of IMGN779 for acute myeloid leukemia in mid-2017 and to file an IND for IMGN632 in the third quarter."

Recent highlights include:

Proprietary Portfolio

First patient dosed in the Phase 3 FORWARD I registration trial of mirvetuximab soravtansine in platinum-resistant ovarian cancer (January 2017);
Publication of results of the mirvetuximab soravtansine Phase 1 expansion cohort in the Journal of Clinical Oncology (December 2016);
Oral and poster presentations highlighting preclinical data for IMGN632 at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (December 2016), demonstrating exceptional activity in acute myeloid leukemia (AML) models, including those resistant to standard of care therapies, as well as reduced toxicity to human marrow progenitor cells, compared to a DNA-crosslinking payload while maintaining similar potency;
Presentation of preclinical data at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 2016 conference demonstrating the potential for enhanced activity when combining mirvetuximab soravtansine with immune checkpoint inhibition (November 2016).
Partner Programs

Sanofi advancing isatuximab (SAR650984), a CD38-targeting antibody, in combination with pom-dex to a Phase 3 clinical trial in multiple myeloma (Q4 2016); and
Novartis dosing the first patient with HKT288, a CDH6-targeting ADC, in a Phase 1 clinical trial in ovarian cancer and renal cell carcinoma (December 2016).
Upcoming anticipated events include:

Activation of more than 100 sites in North America and Western Europe to enable the rapid enrollment of patients to the mirvetuximab soravtansine Phase 3 FORWARD I trial;
Presentation of:
Expanded Phase 1 data from the biopsy cohort for mirvetuximab soravtansine at the Society of Gynecologic Oncology (SGO) annual meeting (March 2017);
Nine posters highlighting ImmunoGen’s technology and innovation in ADCs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting (April 2017);
Initial data from the Company’s Phase 1b/2 FORWARD II trial evaluating mirvetuximab soravtansine in combination with Avastin, carboplatin, Doxil or Keytruda (Q2 2017);
Pooled data from over 100 ovarian cancer patients treated in multiple mirvetuximab soravtansine Phase 1 cohorts and data from the Phase 1 steroid eye drop expansion cohort (Q2 2017);
Initial Phase 1 data for IMGN779, a CD33-targeting ADC, for the treatment of AML (mid-2017), which will be the first clinical data reported with an ADC using ImmunoGen’s DNA-alkylating payload;
Filing of an IND to initiate clinical testing with IMGN632, a CD123-targeting ADC integrating a more potent DNA-alkylating payload (Q3 2017).
Financial Results

As previously disclosed, effective January 1, 2017, ImmunoGen transitioned to a fiscal year ending December 31. Revenues for the six month transition period ended December 31, 2016 were $21.5 million, compared to $32.9 million for the six months ended December 31, 2015. License and milestone fees for the current period include a $5 million partner milestone payment achieved compared to $8.6 million of amortization of upfront fees received from Takeda and $8 million from partner milestone payments in the prior period. Revenues in the current period include $12.9 million of non-cash royalty revenues, compared with $12.0 million in non-cash royalty revenues and $0.2 million in cash royalty revenues for the prior period. Revenues for the current period also include $2.8 million of research and development support fees and $0.7 million of clinical materials revenue, compared with $1.6 million and $2.3 million, respectively, in the prior period.

Operating expenses for the six month transition period ended December 31, 2016 were $89.0 million, compared to $89.7 million for the six months ended December 31, 2015. Operating expenses in the current period include research and development expenses of $66.6 million, compared to $73.3 million in the prior period. This change is primarily due to a decrease in third-party costs resulting from activities performed in the prior period to support pivotal development for mirvetuximab soravtansine, decreased costs associated with manufacturing clinical materials on behalf of our partners, and decreased cytotoxic and antibody costs due to timing of supply requirements. Operating expenses include general and administrative expenses of $18.0 million in the current period, compared to $16.4 million in the prior period. This increase is primarily due to $2.4 million of one-time third-party service fees incurred relating to the Company’s strategic review and resulting restructuring activities, partially offset by lower salaries and related expenses and lower administrative expenses. Operating expenses in the current period correspondingly include a $4.4 million restructuring charge, which includes costs related to a 17% workforce reduction and a $1 million impairment loss on leasehold improvements related to leased office space that the Company will not occupy and will seek to sublease.

ImmunoGen reported a net loss of $78.9 million, or $0.91 per basic and diluted share, for the Company’s six month fiscal year transition period ended December 31, 2016 compared to a net loss of $67.0 million, or $0.77 per basic and diluted share, for the same period last year.

ImmunoGen had approximately $160.0 million in cash and cash equivalents as of December 31, 2016, compared with $245.0 million as of June 30, 2016, and had $100.0 million of convertible debt outstanding in each period. Cash used in operations was $83.7 million for the six months ended December 31, 2016, compared with $65.5 million for the six months ended December 31, 2015. Capital expenditures were $1.4 million and $5.1 million for the six months ended December 31, 2016 and 2015, respectively.

Financial Guidance

For 2017, ImmunoGen expects:

revenues between $70 million and $75 million, which includes $28 million of expected upfront and milestone fees from our partners;
operating expenses between $175 million and $180 million; and
cash and marketable securities at December 31, 2017 between $35 million and $40 million.
ImmunoGen expects that its current cash plus expected cash revenues from partners and collaborators will enable the Company to fund operations into the second quarter of 2018.

Heat Biologics Presents Immune Data on its HS-410 Phase 2 Bladder Cancer Trial at the Genitourinary Cancers Symposium

On February 17, 2017 Heat Biologics, Inc. ("Heat") (Nasdaq:HTBX), reported that it presented a poster of its immunological data from its 94-patient Phase 2 trial evaluating vesigenurtacel-L (HS-410) either alone or in combination with BCG in patients with non-muscle invasive bladder cancer (NMIBC) at the 2017 Genitourinary (GU) Cancers Symposium (Press release, Heat Biologics, FEB 17, 2017, View Source [SID1234517757]). Researchers reported that HS-410, in combination with BCG, continues to be generally well-tolerated, that HS-410 activates CD8+ T cells and that these immune responders appear to have a lower recurrence rate than non-immune responders. Taken together, these data strengthen support for the vaccine mechanism of action and clinical proof-of-concept of immune activation.

Patients were also evaluated based on their levels of tumor infiltrating lymphocytes (TIL) at the start of treatment. In the placebo arm, patients with low TIL levels at baseline had a higher incidence of disease recurrence than patients with high TIL levels at baseline. However, in the vaccine-treated group, recurrence levels were essentially the same between the high and low TIL subgroups, at 25% and 29%, respectively. The fact that these two groups of patients saw clinical outcomes that were roughly identical may warrant further evaluation.

"These data continue to support our hypothesized vaccine mechanism of action," said Jeff Hutchins, Ph.D., Heat’s Chief Scientific Officer and Senior Vice President of Preclinical Development. "Furthermore, we believe this vaccine treatment strategy could be evaluated in more advanced bladder patient populations, where immunotherapy has been shown to be effective, but where not all patients respond to therapy, likely due to insufficient T cell activation and proliferation."

As previously reported, vaccine arms did not show a statistical improvement over the placebo arm in the primary endpoint (1-year recurrence free survival). However, in keeping with clinical trial guidance, Heat continues to monitor all patients enrolled in the study for a 2-year duration.

The poster will be uploaded to the publications section of Heat’s corporate website in line with the conference’s embargo policy.

Myriad’s BRACAnalysis CDxÂ® Test Successfully Identified Metastatic Breast Cancer Patients with Improved Outcomes from AstraZeneca’s PARP Inhibitor, Olaparib

On February 17, 2017 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported new findings from the OlympiAD study that show its BRACAnalysis CDx test successfully identified patients with HER2-negative metastatic breast cancer who have BRCA mutations and who had improved response with Lynparza (olaparib), AstraZeneca’s PARP inhibitor (Press release, Myriad Genetics, FEB 17, 2017, View Source [SID1234517753]).

The high level results — announced earlier today from AstraZeneca — are the first reported clinical data from the OlympiAD study (NCT02000622), which assessed the efficacy and safety of olaparib monotherapy versus physicians’ choice of chemotherapy (i.e., capecitabine, vinorelbine or eribulin) in the treatment of metastatic breast cancer. Of the 302 patients in the study, 98 percent (297/302) tested positive for germline BRCA1/2 mutations as determined by Myriad’s FDA-approved BRACAnalysis CDx test. The results demonstrated a statistically-significant improvement of progression-free survival (PFS) among BRCA-mutated patients treated with olaparib compared to those treated with physicians’ choice.

"We believe the results of the OlympiAD trial support use of the BRACAnalysis CDx test to help inform treatment decisions in the metastatic breast cancer setting and will expand the patient population who can benefit from BRCA testing," said Johnathan Lancaster, M.D., Ph.D., chief medical officer of Myriad Genetic Laboratories. "This study underscores Myriad’s commitment to our pharmaceutical partners and to advancing the field of personalized medicine so that new effective treatment options are available to patients."

It is estimated there are approximately 60,000 patients with metastatic breast cancer, two thirds of whom are not currently eligible for BRCA testing based upon family and personal history alone or current testing criteria. If approved as a new indication this would triple the number of patients with metastatic breast cancer who would benefit from BRCA testing.

The ongoing collaboration between Myriad and AstraZeneca to develop a novel companion diagnostic test to identify candidates for treatment with olaparib began in 2007. In Dec. 2014, Myriad received FDA approval for BRACAnalysis CDx to help identify patients with advanced ovarian cancer who are eligible for fourth-line treatment with olaparib. BRACAnalysis CDx is Myriad’s first FDA-approved companion diagnostic and was the first-ever laboratory developed test reviewed and approved by the FDA.

About BRACAnalysis CDx
BRACAnalysis CDx is an in vitro diagnostic device intended for the qualitative detection and classification of variants in the protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes using genomic DNA obtained from whole blood specimens collected in EDTA. Single nucleotide variants and small insertions and deletions (indels) are identified by polymerase chain reaction (PCR) and Sanger sequencing. Large deletions and duplications in BRCA1 and BRCA2 are detected using multiplex PCR. Results of the test are used as an aid in identifying ovarian cancer patients with deleterious or suspected deleterious germline BRCA variants eligible for treatment with Lynparza (olaparib). This assay is for professional use only and is to be performed only at Myriad Genetic Laboratories, a single laboratory site located at 320 Wakara Way, Salt Lake City, UT 84108.

About Lynparza
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells. Lynparza is currently approved by regulatory health authorities in the EU for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. It is also approved in the US as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated (as detected by an FDA-
test) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Lynparza is currently being investigated in another separate non-metastatic breast cancer Phase III study called OLYMPIA. This study is still open and recruiting patients internationally.

Phase II study supports potential for Roche’s TECENTRIQ (atezolizumab) plus Avastin (bevacizumab) for people with locally advanced or metastatic renal cell carcinoma

On February 18, 2107 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported encouraging results from the Phase II IMmotion150 study that compared TECENTRIQ (atezolizumab) plus Avastin (bevacizumab) and TECENTRIQ monotherapy to sunitinib alone in people with previously untreated, locally advanced or metastatic renal cell carcinoma (mRCC) (Press release, Hoffmann-La Roche, FEB 17, 2017, View Source [SID1234517752]). These results were presented at the 2017 Genitourinary Cancers Symposium taking place from February 16-18 in Florida, USA.

IMmotion150 is the first randomised clinical trial to evaluate the combination of TECENTRIQ and Avastin in mRCC. The study was designed to inform further clinical development of this combination and these study results reinforce the potential of this combination in this setting.

The study showed that people whose disease expressed PD-L1 (programmed death-ligand 1) and were treated with TECENTRIQ plus Avastin had a 36 percent reduction in the risk of their disease worsening or death compared to people treated with sunitinib alone (median progression-free survival [mPFS]: 14.7 vs. 7.8 months; HR= 0.64; 95% CI 0.38, 1.08). No PFS advantage was observed compared to sunitinib in the intention-to-treat [ITT] population (mPFS: 11.7 vs. 8.4 months; HR = 1.00; 95% CI 0.69, 1.45). Median Duration of Response (DoR) has not yet been reached after 20.7 months of follow-up across treatment arms. Adverse events in the TECENTRIQ plus Avastin arm were consistent with those observed in previous studies of each medicine.

"These Phase II results support the scientific rationale for potentially combining TECENTRIQ and Avastin in people with this type of kidney cancer," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "There is a significant need for new treatment options for people living with advanced RCC, a disease where currently only about one in 10 people are alive beyond five years following diagnosis."

Roche is also evaluating TECENTRIQ plus Avastin vs sunitinib in a Phase III study (IMmotion151; NCT02420821) in people with previously untreated, locally advanced or metastatic RCC. A study of TECENTRIQ as adjuvant treatment for RCC began enrolling earlier this year.

About the IMmotion150 study
IMmotion150 is a global, multicentre, open-label, randomised Phase II study that was designed to evaluate the efficacy and safety of TECENTRIQ plus Avastin (Arm A), TECENTRIQ alone (Arm B) or sunitinib alone (Arm C) in 305 patients with previously untreated, locally advanced or metastatic RCC. People in Arm A received TECENTRIQ administered intravenously at 1200 mg every 3 weeks (6-week cycles) plus Avastin intravenously at 15 mg until disease progression or lack of clinical benefit. People in Arm B received TECENTRIQ alone (until disease progression or lack of clinical benefit), and people in Arm C received sunitinib 50 mg orally daily for 4 weeks followed by 2 weeks rest until disease progression.

The co-primary endpoints were PFS per RECIST v.1.1 via Independent Review Facility (IRF) assessment in all randomised patients (ITT population) and in the PD-L1 selected (IC1/2/3) subgroup. PD-L1 expression was assessed on tumour-infiltrating immune cells (IC) with an investigational immunohistochemistry (IHC) test based on the SP142 antibody being developed by Roche Tissue Diagnostics. Secondary endpoints included IRF-assessed overall response rate (ORR) and duration of response (DoR), investigator-assessed PFS, ORR, DoR and safety, and overall survival (OS). A summary of the efficacy data from Arms A, B and C of the IMmotion150 study is included below.

IMmotion150 was designed with planned crossover. Over three quarters (78 percent) of sunitinib patients (Arm C) who progressed subsequently received TECENTRIQ plus Avastin (Arm A) OS results were immature at time of analysis with only 35 percent of events having occurred.

Safety in the TECENTRIQ plus Avastin arm appeared consistent with the known safety profile of the individual medicines. No new safety signals were identified. Frequency of all-grade treatment-related adverse events was similar between arms. The most common AE’s occurring in more than 20% of patients receiving Tecentriq plus Avastin and with a greater than 5% increase when compared to sunitinib included: arthralgia (38%), proteinuria (36%), epistaxis (28%), and pruritus (22%). Frequency of grade 3-4 AEs regardless of relationship to treatment were similar between patients treated with TECENTRIQ plus Avastin (63%) and sunitinib (69%). Treatment-related grade 3-4 events reported in 40% of TECENTRIQ plus Avastin treated patients and 57% of sunitinib treated patients. One person who was treated with TECENTRIQ plus Avastin experienced intracranial haemorrhage that led to death. Fifteen of 101 patients (15%) treated with TECENTRIQ plus Avastin discontinued treatment for adverse events.

About renal cell carcinoma
Renal cell carcinoma (RCC) is the most common type of kidney cancer and forms when abnormal cells develop in the small tubes (known as renal tubules) in the kidneys. Each year about 338,000 people are diagnosed with kidney cancer globally accounting for nearly 145,000 deaths worldwide.1 The disease is more prevalent in males and people aged 55–74 years.2 Currently there is a significant need for more effective treatments with only about one in ten people alive five years post diagnosis.2

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.

About Avastin
With the initial approval for advanced colorectal cancer in 2004, Avastin became the first anti-angiogenic therapy made widely available for the treatment of patients with an advanced cancer. Today, Avastin is continuing to transform cancer care across the world through its proven survival benefit (overall survival and/or progression free survival) in several types of cancer, including colorectal cancer, non-small cell lung cancer, kidney cancer, breast cancer, ovarian cancer, cervical cancer, and glioblastoma. Avastin has made anti-angiogenic therapy a fundamental pillar of cancer treatment today with over 2.4 million patients treated with this medicine so far. With one of the largest clinical development programmes ever seen in oncology, Avastin will continue to transform how patients are treated as ongoing studies seek to understand the full potential of this medicine and its combinations with the most cutting edge therapies in development.

Exelixis Announces Phase 1 Trial Results for Cabozantinib in Combination with Nivolumab with or without Ipilimumab in Refractory Metastatic Urothelial Carcinoma and Other Genitourinary Tumors

On February 17, 2017 Exelixis, Inc. (NASDAQ:EXEL) reported results from a phase 1 trial of cabozantinib in combination with either nivolumab or nivolumab plus ipilimumab in patients with refractory genitourinary tumors (Press release, Exelixis, FEB 17, 2017, View Source [SID1234517749]). The primary endpoint of the trial is to determine the dose limiting toxicity (DLT) and recommended phase 2 doses of the doublet and triplet combinations. The findings were presented during a poster session (Abstract #293) on February 17 at the 2017 Genitourinary Cancers Symposium, which is being held in Orlando, Florida, February 16 – 18, 2017.

Between July 22, 2015 and December 31, 2016, 48 patients were accrued with previously treated metastatic urothelial carcinoma (mUC, n=19), urachal adenocarcinoma (n=4), squamous cell carcinoma of the bladder or urethra (n=2), germ cell tumor (n=4), castration-resistant prostate cancer (n=9), renal cell carcinoma (n=4), trophoblastic tumor (n=1), sertoli cell tumor (n=1) or penile squamous cell carcinoma (n=4) and treated in two parts. In Part I, 30 patients were treated with the doublet combination of cabozantinib and nivolumab at four dose levels. In Part II, 18 patients were treated with the triplet combination of cabozantinib, nivolumab and ipilimumab at three dose levels.

Among the 43 patients who were evaluable for response, the objective response rate (ORR) for all tumor types was 30 percent (38 percent for the doublet dosing schedule and 18 percent for the triplet dosing schedule), with a 7 percent complete response (CR) rate and a 23 percent partial response (PR) rate. Stable disease (SD) was reported in 56 percent of patients. The ORR for patients with mUC was 38 percent, and 2 of 16 patients achieved a CR, while 2 patients with squamous cell carcinoma of the bladder had objective responses (1 CR and 1 PR). In the mUC cohort, 15 of 16 patients had a CR, PR or SD as their best response.

Grade 3 adverse events (>5 percent of patients) observed in the doublet combination included neutropenia (17 percent), hypophosphatemia (13 percent), hypertension (10 percent), lipase increase (7 percent), fatigue (7 percent), diarrhea (7 percent) and dehydration (7 percent). Grade 3 adverse events (>5 percent of patients) observed in the triplet combination included hypertension (17 percent), hypophosphatemia (17 percent), fatigue (13 percent), hyponatremia (13 percent), lipase increase (13 percent), nausea (13 percent) and rash (6 percent). There were limited numbers of grade 4 adverse events (10 percent including thrombocytopenia and lipase increase in the doublet combination, and 6 percent (lipase increase) in the triplet combination), and no grade 5 adverse events observed in either part of the trial.

"There is a significant unmet need for treatment regimens that can slow tumor progression in advanced, intractable cancers such as metastatic urothelial carcinoma. The use of combination therapies may be a strategy that could increase anti-tumor activity in these patients," said Andrea Apolo, M.D., Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, the principal investigator of the trial. "Previously reported data from Part I of the trial showed that cabozantinib in combination with nivolumab provided an encouraging objective response rate and tolerability profile across a diverse range of genitourinary tumors. Data from Part II also demonstrate that using cabozantinib with two immunotherapy agents is well-tolerated with promising early activity. These results support the further evaluation of both regimens in these tumor types."

The recommended doses for the ongoing expansion cohorts were determined to be cabozantinib 40 mg daily plus nivolumab 3 mg/kg once every 2 weeks for the doublet and cabozantinib 40 mg daily, nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses, then nivolumab 3 mg/kg every 2 weeks for the triplet.

"These early clinical results generated by our collaborators at the NCI-CTEP suggest that the combination of cabozantinib with either nivolumab or nivolumab and ipilimumab in patients with genitourinary malignancies is associated with an encouraging tolerability, safety and activity profile," said Michael M. Morrissey, Ph.D., president and Chief Executive Officer of Exelixis. "With these results in hand, we are committed to further examining the potential of cabozantinib in combination with a variety of immunotherapies to treat a broad range of genitourinary and other cancers."

About the Trial

The trial is sponsored by the U.S. National Cancer Institute (NCI) through Cooperative Research and Development Agreements between the NCI’s Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis, and both Bristol-Myers Squibb and Exelixis. Andrea Apolo, M.D., of the NCI’s Genitourinary Malignancies Branch, is the principal investigator. The trial is being conducted by the NCI and includes centers from its Experimental Therapeutics Clinical Trials Network.

The primary endpoint of the phase 1 trial is to determine the dose limiting toxicity (DLT) and recommended phase 2 doses of the doublet and triplet combinations. The secondary endpoint is clinical response rate as assessed by RECIST 1.1. Part I of the study included four dosing levels: cabozantinib 40 mg daily plus nivolumab 1 mg/kg once every 2 weeks; cabozantinib 40 mg daily plus nivolumab 3 mg/kg once every 2 weeks; cabozantinib 60 mg daily plus nivolumab 1 mg/kg once every 2 weeks; and cabozantinib 60 mg daily plus nivolumab 3 mg/kg once every 2 weeks.

Part II of the study included three dosing levels: cabozantinib 40 mg daily, nivolumab 1 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses, then nivolumab 1 mg/kg every 2 weeks; cabozantinib 40 mg daily, nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses, then nivolumab 3 mg/kg every 2 weeks; and cabozantinib 60 mg daily, nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses, then nivolumab 3 mg/kg every 2 weeks.

Data from Part I of the study evaluating the combination of cabozantinib with nivolumab in patients with previously treated genitourinary tumors were presented by Dr. Apolo at the European Society for Medical Oncology 2016 Congress. Expansion cohorts assessing cabozantinib and nivolumab are currently being accrued with bladder, renal and rare genitourinary cancer patients. Data from these patients will be reported at a later date.

About Genitourinary Cancers

Genitourinary cancers are those that affect the urinary tract, bladder, kidneys, ureter, prostate, testicles, penis or adrenal glands — parts of the body involved in reproduction and excretion — and include renal cell carcinoma and urothelial carcinoma.1

Kidney cancer is among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S., according to the American Cancer Society’s 2016 statistics.2 Clear cell renal cell carcinoma is the most common type of kidney cancer in adults.3 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.2 Approximately 30,000 patients in the U.S. and 68,000 globally require treatment.4

Prostate cancer is the second most common cause of cancer death in men, behind only skin cancer.5 There is a high survival rate for patients when prostate cancer is detected early, but once the disease has spread to other parts of the body the five-year survival rate is just 28 percent.6 Approximately 2,850,000 men were living with prostate cancer in the U.S. in 2013,7 and 180,000 new cases are diagnosed each year.5

Urothelial cancers encompass carcinomas of the bladder, ureter and renal pelvis at a ratio of 50:3:1, respectively.8 Urothelial carcinoma occurs mainly in older people, with 90 percent of patients aged 55 or older.9 Bladder cancer is the fourth most common cancer in men and accounts for about five percent of all new cases of cancer in the U.S. each year.9 In 2013, an estimated 587,426 people were living with bladder cancer in the U.S.10

About CABOMETYX (cabozantinib)

CABOMETYX is the tablet formulation of cabozantinib. Its 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 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 September 9, 2016, the European Commission approved CABOMETYX tablets for the treatment of advanced renal cell carcinoma in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy in the European Union, Norway and Iceland. 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. On December 21, 2016, this agreement was amended to include commercialization rights for Ipsen in Canada. On January 30, 2017, Exelixis and Takeda Pharmaceutical Company Limited announced an exclusive licensing agreement for the commercialization and further clinical development of cabozantinib for all future indications in Japan, including RCC.

Cabozantinib is not indicated for the treatment of refractory mUC and other genitourinary tumors.

U.S. 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.

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