On June 3, 2018 FibroGen, Inc. (NASDAQ: FGEN), a biopharmaceutical company, reported Phase 1/2 clinical trial results of pamrevlumab in combination with standard-of-care chemotherapy in patients with locally advanced unresectable pancreatic cancer (LAPC) (Press release, FibroGen, JUN 3, 2018, View Source [SID1234527124]). . Principal investigator Vincent J. Picozzi, Jr., M.D., Director, Pancreas Center of Excellence, Virginia Mason Cancer & Digestive Diseases Institutes, presented the results in a discussion poster session at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago. Pamrevlumab is a proprietary first-in-class antibody targeting connective tissue growth factor (CTGF) under development for the treatment of fibrosis and fibroproliferative disorders.

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"These are some of the most exciting clinical trial results in locally advanced pancreatic cancer I have seen since I began treating pancreatic cancer patients," said Dr. Picozzi. "The data suggest that pamrevlumab in combination with chemotherapy has the potential to become a neoadjuvant treatment regimen for locally advanced unresectable pancreatic cancer patients that has not existed before."

Patients with locally advanced pancreatic cancer (without metastasis) tend to have a poor prognosis with a median survival of 9–18 months. In patients who have undergone resection of their tumor, median survival and five-year survival rates have been reported to be higher than those without resection. Therefore, treatment to achieve a surgical resection in this patient population is a meaningful treatment goal to potentially achieve a favorable overall survival outcome.

In this open-label, randomized Phase 1/2 study, pamrevlumab was administered in combination with standard-of-care chemotherapy (gemcitabine and nab-paclitaxel) and compared to treatment with chemotherapy alone in patients with locally advanced pancreatic ductal adenocarcinoma, who were not eligible for surgical resection based on histology, computerized tomography (CT) scans, and laparoscopy criteria, prior to randomization. Upon completion of the six months of study drug treatment, patients underwent surgical eligibility assessment based on pre-specified objective criteria. The study enrolled 37 patients: 24 received pamrevlumab + chemotherapy: 13 received chemotherapy alone.

At ASCO (Free ASCO Whitepaper) 2018, FibroGen reported that a higher proportion of patients whose tumor was previously considered unresectable became eligible for resection (based on protocol pre-specified post-treatment surgical eligibility criteria) after receiving pamrevlumab and chemotherapy than after receiving chemotherapy alone (at the end of 6 months of treatment), 70.8% vs. 15.4%. For those patients who met these surgical resection eligibility criteria at post-treatment assessment, individual patient condition and circumstance contributed to whether resection subsequently occurred. A higher proportion of pamrevlumab-treated patients achieved surgical resection than those received chemotherapy alone, 33.3% vs. 7.7%.

In the study, patients were followed for survival after evaluation for eligibility for resection and, when applicable, after resection. Patients who had successful resections in this study had a statistically significant longer median survival benefit as compared to patients who did not undergo resection, 40 months vs.18.6 months (p=0.0141), as of May, 2018. FibroGen is continuing to monitor study patients for survival.

"Patients with unresectable locally advanced pancreatic cancer are in need of an innovative and effective treatment with the potential to transform non-operable cancer into resectable disease," said Elias Kouchakji, M.D., Senior Vice President, Clinical Development and Drug Safety. "The updated clinical results we are reporting at ASCO (Free ASCO Whitepaper) suggest that pamrevlumab may improve the treatment outcomes for patients who are currently deemed unresectable."

About Locally Advanced Pancreatic Cancer

In locally advanced pancreatic cancer (LAPC), tumors typically encase structures, particularly blood vessels that are closely associated with the pancreas such as the superior mesenteric artery and superior mesenteric vein. Involvement of the cancer around these blood vessels precludes surgical removal of the tumor. Approximately 80% of newly diagnosed LAPC patients are classified as having unresectable disease, and patients with unresectable LAPC have a median survival only slightly better than that of patients with metastatic pancreatic cancer. Patients with resectable cancer whose tumors are surgically removed have a much better prognosis, with median survival of approximately 23 months, and some patients being cured.

About Pamrevlumab

Pamrevlumab is a first-in-class antibody developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF), a common factor in fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. Pamrevlumab is advancing towards Phase 3 clinical development for the treatment of idiopathic pulmonary fibrosis (IPF) and pancreatic cancer, and has been granted Orphan Drug Designation (ODD) in each of these indications, and is currently in a Phase 2 trial for Duchenne muscular dystrophy (DMD). Pamrevlumab recently received Fast Track designation from the U.S. Food and Drug Administration for the treatment of patients with locally advanced unresectable pancreatic cancer. Pamrevlumab has demonstrated a good safety and tolerability profile in multiple Phase 2 trials conducted to date. For information about pamrevlumab studies currently recruiting patients, please visit www.clinicaltrials.gov.

On June 3, 2018 Polaris Group reported results from a phase 1 clinical study, showing that Polaris lead therapeutic candidate ADI‑PEG 20 in combination with FOLFOX demonstrated promising efficacy for heavily pre-treated hepatocellular carcinoma (HCC) patients (Press release, Polaris Pharmaceuticals, JUN 3, 2018, View Source [SID1234527209]). The results were presented by Dr. James Harding from Memorial Sloan Kettering Cancer Center at the American Society Clinical Oncology’s 2018 annual meeting.

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Overall, 38 HCC patients who have failed at least one line of prior systemic treatment were enrolled and a partial response (PR) was observed in 8 (21.0%), including two in Taiwan. Of the 38, 21 had failed at least two lines of prior systemic treatment, and PRs were observed in 5/21 (23.8%). Currently, all 5 of the third-line or later PR patients are still alive, with 4 of 5 still undergoing treatment and 2 having now maintained a PR for over two years; thus suggesting responses can potentially be durable.

Side effects of the combination have been what would be expected for FOLFOX only, except for injection site reactions consistent with ADI‑PEG 20’s intramuscular route of administration.

Given these encouraging results, a meeting was held with the United States Food & Drug Administration (FDA). Based on this meeting, the study has been expanded into a global, phase 2, single-arm study to support accelerated approval for HCC patients who have failed at least two lines of prior systemic therapies. This study is currently enrolling patients in the US and Taiwan, and will be expanded into UK, Italy, Korea and China.

"ADI‑PEG 20 plus FOLFOX is showing more favorable efficacy compared to historic controls and the combination remains well tolerated. We appreciate the helpful comments of the FDA in assisting us to craft the phase 2 portion of this protocol", said John Bomalaski, M.D., Executive Vice President, Medical Affairs, of Polaris. "We now have a number of clinical trials underway with ADI‑PEG 20 in combination with standard of care agents in multiple cancer indications. These other studies have also shown that ADI‑PEG 20 in combination with multiple chemotherapy agents is well tolerated, and highly improves response rates. We are committed to developing an effective treatment for the 3rd-line or later HCC patients who have no approved treatment option", he added.

About ADI‑PEG 20

ADI‑PEG 20 is a biologic being developed by Polaris Group to treat cancers carrying a major metabolic defect that renders them unable to internally synthesize arginine. Because arginine is essential for protein synthesis and survival of cells, these cancer cells become dependent upon the external supply of arginine to survive and grow. ADI‑PEG 20 is designed to deplete the external supply of arginine, causing arginine-dependent cancer cells to die while leaving the patient’s normal cells unharmed. Multiple cancers have been reported to have a high degree of arginine-dependency and can potentially be treated with ADI‑PEG 20.

On June 3, 2018 Exelixis, Inc. (Nasdaq: EXEL) reported results from sub-group analyses of the CELESTIAL phase 3 pivotal trial of cabozantinib in advanced hepatocellular carcinoma (HCC) comparing outcomes by duration of sorafenib treatment in patients whose only prior treatment was sorafenib and outcomes based on age (Press release, Exelixis, JUN 3, 2018, View Source;p=RssLanding&cat=news&id=2352879 [SID1234527074]). The findings, presented in two posters at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting during the Gastrointestinal (Noncolorectal) Cancer Poster Session from 8:00 – 11:00 a.m. CDT in Hall A, showed that cabozantinib improved overall survival (OS) and progression-free survival (PFS) compared with placebo irrespective of duration of prior sorafenib treatment or age category.

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"We’re pleased with the encouraging CELESTIAL subgroup data presented at ASCO (Free ASCO Whitepaper), which showed that cabozantinib provided benefits to patients regardless of duration of prior sorafenib treatment or age," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "We continue to work closely with the U.S. FDA as they review the filing application for cabozantinib for previously treated advanced hepatocellular carcinoma and hope it may soon provide a new option for patients with this difficult-to-treat cancer who have few alternatives."

Outcomes in Patients who had Received Sorafenib [abstract 4088]

The sub-analysis of patients in CELESTIAL who received sorafenib as their only prior systemic therapy was presented by Robin Kate Kelley, M.D., University of California San Francisco. In this subgroup-analysis, patients were grouped by the length of time they had been treated with sorafenib (less than three months; three to six months; more than six months) to assess the effect of cabozantinib in patients with varying benefit from prior sorafenib. In all three groups, cabozantinib improved OS and PFS versus placebo:

Treatment-related grade 3 or 4 adverse events (AEs) that occurred in at least 5 percent of any patient group were palmar-plantar erythrodysesthesia, aspartate aminotransferase increased, hypertension, fatigue, decreased appetite, diarrhea, asthenia and anemia.

Outcomes in Patients Based on Age [abstract 4090]

The sub-analysis evaluating patients in the CELESTIAL trial based on age was presented by Lorenza Rimassa, M.D., Humanitas Clinical and Research Center. In this sub-analysis, patients were grouped as younger than 65 years of age and 65 years of age and older. The findings showed OS and PFS were consistently improved with cabozantinib versus placebo in each age category:

Treatment-related grade 3 or 4 AEs occurred in at least 5 percent of either age group and were similar in nature and frequency to the AEs that occurred in patients who received sorafenib as their only prior systemic therapy.

An encore of the CELESTIAL trial data originally presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI) will be presented by Dr. Ghassan K. Abou-Alfa, Memorial Sloan Kettering Cancer Center, during the Gastrointestinal (Noncolorectal) Cancer Poster Discussion Session today from 4:45 – 6:00 p.m. CDT in Hall D2 [abstract 4019].

The CELESTIAL trial was the basis for Exelixis’ supplemental New Drug Application filed with the U.S. Food and Drug Administration (FDA) for CABOMETYX (cabozantinib) tablets as a treatment for patients with previously treated advanced HCC. The Prescription Drug User Fee Act action date for this application is January 14, 2019. On March 28, 2018, our partner Ipsen announced that they received validation of the application for variation to the CABOMETYX marketing authorization from the European Medicines Agency, the European regulatory authority, for the addition of a new indication for patients with previously treated advanced HCC.

About the CELESTIAL Study

CELESTIAL is a phase 3 randomized, double-blind, placebo-controlled study of cabozantinib in patients with advanced HCC conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who received prior sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms during the blinded treatment phase of the trial. The primary endpoint for the trial is overall survival, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.

Results of the trial were first presented by Dr. Abou-Alfa at 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in January 2018.

About HCC

Liver cancer is the second-leading cause of cancer death worldwide, accounting for more than 700,000 deaths and nearly 800,000 new cases each year.1 In the U.S., the incidence of liver cancer has more than tripled since 1980.2 HCC is the most common form of liver cancer, making up about three-fourths of the estimated nearly 42,000 new cases in the U.S. in 2018. HCC is the fastest-rising cause of cancer-related death in U.S.3 Without treatment, patients with advanced HCC usually survive less than 6 months.4

About CABOMETYX (cabozantinib)

CABOMETYX tablets are approved in the United States for the treatment of patients with advanced RCC. CABOMETYX tablets are also approved in the European Union, Norway, Iceland, Australia, Switzerland and South Korea for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy, and in the European Union for previously untreated intermediate- or poor-risk advanced RCC. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan, including RCC and HCC.

Please see Important Safety Information below and full U.S. prescribing information at View Source

U.S. Important Safety Information

Hemorrhage: Severe and fatal hemorrhages have occurred with CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic events was 3% in CABOMETYX-treated patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
Gastrointestinal (GI) Perforations and Fistulas: In RCC studies, fistulas were reported in 1% of CABOMETYX-treated patients. Fatal perforations occurred in patients treated with CABOMETYX. In RCC studies, gastrointestinal (GI) perforations were reported in 1% of CABOMETYX-treated patients. Monitor patients for symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula which cannot be appropriately managed or a GI perforation.
Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. In RCC studies, venous thromboembolism occurred in 9% (including 5% pulmonary embolism) and arterial thromboembolism occurred in 1% of CABOMETYX-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, including hypertensive crisis. In RCC studies, hypertension was reported in 44% (18% Grade ≥ 3) of CABOMETYX-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: In RCC studies, diarrhea occurred in 74% of patients treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients treated with CABOMETYX. 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.
Palmar-Plantar Erythrodysesthesia (PPE): In RCC studies, palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume CABOMETYX at a reduced dose.
Reversible Posterior Leukoencephalopathy Syndrome (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 may be associated with CABOMETYX. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during CABOMETYX treatment and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, hypertension, PPE, weight decreased, vomiting, dysgeusia, and stomatitis.
Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
Lactation: Advise women not to breastfeed while taking CABOMETYX and for 4 months after the final dose.
Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

On June 3, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported findings today from a Phase 2 study that showed treatment with erdafitinib resulted in durable responses in patients with metastatic or surgically unresectable urothelial cancer (mUC) and fibroblast growth factor receptor alterations (FGFRalt) (Press release, Johnson & Johnson, JUN 3, 2018, View Source [SID1234527110]). This is a patient population with high unmet need based on poor outcomes when treated with available therapies. Erdafitinib is a once-daily pan-FGFR inhibitor.1 FGFRs are cell proteins that, if altered, can contribute to the development of cancer.1 Alterations occur in approximately 20 percent of mUC patients.1 The results were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting in Chicago (Abstract #4503) and have been selected for the Best of ASCO (Free ASCO Whitepaper) Meetings.1

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"These study results are very promising, particularly as this is an area of high unmet need with patients who otherwise have very limited treatment options remaining. We hope that the response rates shown by erdafitinib could eventually give patients with metastatic or surgically unresectable urothelial cancer a new treatment option"

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"I am very encouraged by these Phase 2 data showing that erdafitinib had promising response rates and progression-free survival in a patient population with such high unmet need," said Dr. Yohann Loriot, Senior Consultant, Department of Cancer Medicine & INSERM, Institut Gustave Roussy, University of Paris Sud, Villejuif, France. "Currently there are no targeted therapies approved for specific subsets of patients with urothelial cancer who have genetic alterations. While immune checkpoint inhibitors have led to improvements in outcomes for these patients, we are still finding that many patients do not respond to treatment."

BLC2001 (NCT02365597) is a multicentre, open-label Phase 2 study evaluating the efficacy and safety of erdafitinib in the treatment of adult patients with locally advanced or metastatic urothelial cancer, whose tumours have certain FGFR alterations.1 Ninety-nine patients were treated with an optimised dosing schedule using pharmacodynamically guided dose up-titration: a starting dose of erdafitinib at 8 mg daily, with the possibility to increase the dose to 9 mg daily based on serum phosphate levels.2 Twelve percent of patients were chemo-naïve, 89 percent of patients had received one or more lines of therapy, 43 percent of patients had received two or more prior lines of therapy, and 78 percent of patients had visceral metastases.2 There was a 40 percent confirmed overall response rate1 (RECIST 1.1;* 3% Complete Response, 37% Partial Response), a median progression-free survival of 5.5 months and median overall survival of 13.8 months.2 In patients who experienced grade 3 adverse events (AEs), the most common were, stomatitis (9%) and diarrhoea (4%).1 Seven patients discontinued due to treatment-related AEs.2

"These study results are very promising, particularly as this is an area of high unmet need with patients who otherwise have very limited treatment options remaining. We hope that the response rates shown by erdafitinib could eventually give patients with metastatic or surgically unresectable urothelial cancer a new treatment option," said Dr Ivo Winiger-Candolfi, Europe, Middle East and Africa (EMEA) Oncology Therapeutic Area Lead, Janssen. "The successful development of new oncology therapies, such as erdafitinib, is an example of our precision medicine approach: providing the right patient, with the right treatment, at the right time. We recognise that every patient is unique and that by accounting for individual differences in people’s genes, environments and lifestyles, we can optimise the therapeutic benefit for particular groups of patients. We look forward to understanding the potential efficacy and broader safety profile of erdafitinib in both Phase 3 development as well as in combination with anti-PD1 therapy."

*RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumors which is a standard way to measure how well a cancer patient responds to treatment and is based on whether tumours shrink, stay the same, or get bigger.3

About Urothelial Cancer

Europe has among the highest incidence rates of bladder cancer in the world and mortality rates for men are by far the highest recorded worldwide.4 It is the fifth most frequently diagnosed cancer in the EU, with about 124,000 new cases each year for both sexes.5 The majority (90%) of bladder cancer consists of urothelial carcinoma in Western Europe.6 Urothelial bladder cancer starts in the bladder lining (urothelial cells or transitional cells) and can be non-invasive or invasive.7 For patients with metastatic disease, outcomes can be poor due to the often rapid progression of the tumour and the lack of efficacious treatments.8 The relative five-year survival rate for patients with metastatic disease is five percent.9

About erdafitinib

Erdafitinib is a once-daily oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor being evaluated by Janssen Research & Development in Phase 2 and 3 clinical trials in patients with advanced urothelial cancer.10 FGFRs are a family of receptor tyrosine kinases which may be upregulated in various tumour cell types and may be involved in tumour cell proliferation, tumour angiogenesis and tumour cell survival.11 In 2008, Janssen entered into an exclusive worldwide license and collaboration agreement with Astex Therapeutics Ltd. to develop and commercialise erdafitinib.

Erdafitinib received Breakthrough Therapy Designation from the U.S. Food and Drug Administration in March 2018.12 The aim is to move towards regulatory submission with the Phase 2 data and continue to pursue erdafitinib in Phase 3 clinical development, as well as in combination with anti-PD-1 therapy.

On June 3, 2018 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seattle Genetics, Inc. (Nasdaq: SGEN) reported the presentation of updated phase 1 data of enfortumab vedotin, an investigational antibody-drug conjugate (ADC), at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting in Chicago (Press release, Astellas, JUN 3, 2018, View Source [SID1234527059]). In this phase 1 study (EV-101), enfortumab vedotin was evaluated as monotherapy for patients with metastatic urothelial cancer including patients who previously received a checkpoint inhibitor.i This phase 1 study is part of a broader program focused on investigating enfortumab vedotin in both monotherapy and in combination with a checkpoint inhibitor for locally advanced or metastatic urothelial cancer.

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(PRNewsfoto/Astellas Pharma Inc.)

"Many patients with locally advanced or metastatic urothelial cancer previously treated with checkpoint inhibitors have a poor prognosis and limited subsequent treatment options," said Jonathan E. Rosenberg, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center and presenter of the updated phase 1 data at ASCO (Free ASCO Whitepaper). "Data from the ongoing study support the potential of enfortumab vedotin in locally advanced or metastatic urothelial cancer, based on the objective response rate and preliminary estimates of survival."

"We are encouraged by these updated data for enfortumab vedotin, which further support the rapid expansion of a comprehensive clinical trial program and the registrational study that is already underway in metastatic urothelial cancer," said Steven Benner, M.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development, Astellas. "We look forward to working closely with our partner, Seattle Genetics, as we continue to evaluate enfortumab vedotin for patients with metastatic urothelial cancer."

Robert Lechleider, M.D., Senior Vice President, Clinical Development at Seattle Genetics added, "These ASCO (Free ASCO Whitepaper) data from the phase 1 study of enfortumab vedotin further support its Breakthrough Therapy Designation from the FDA, and the rationale for our ongoing pivotal trial, EV-201. We look forward to completing enrollment of the EV-201 pivotal trial for patients with metastatic urothelial cancer who have received both a platinum-based therapy and a checkpoint inhibitor. Positive data in this patient subgroup may represent a potential expedited registration pathway."

The following updated results were presented by Dr. Rosenberg:

Updated Results from the Enfortumab Vedotin Phase 1 (EV-101) Study in Patients with Metastatic Urothelial Cancer: (Abstract #4504, oral abstract session on Sunday, June 3 from 9:12-9:24 a.m. CT)1

Study Design

A total of 112 patients with metastatic urothelial cancer treated with 1 or more prior chemotherapy or who were ineligible for cisplatin received a 30-minute infusion of enfortumab vedotin at 1.25 mg/kg on day 1, 8 and 15 of each 28-day cycle.ii
Sixty-three percent of patients had received 2 or more prior therapies in the metastatic setting.1
The primary objective of the study was tolerability. A secondary objective was antitumor activity, which was assessed by investigators every 8 weeks.2
Study Results

Of 112 evaluable patients, confirmed complete responses were observed in 4 patients and confirmed partial responses were observed in 41 patients, with an overall response rate of 41 percent.1
The most commonly reported treatment-related adverse event was All Grade fatigue (54 percent). Anemia (8 percent), hyponatremia (7 percent), urinary tract infection (7 percent) and hyperglycemia (6 percent) were the most common ≥ Grade 3 AEs.1 Four patients experienced a fatal treatment-related adverse event (respiratory failure, urinary tract obstruction, diabetic ketoacidosis, multi-organ failure).2
Additionally, the ORR in the 89 patients with prior checkpoint inhibitor therapy was 40 percent, 44 percent in the 23 patients who had not been treated with a checkpoint inhibitor, and 39 percent in the 33 patients with liver metastases.1
For all enrolled patients, the interim median overall survival was 13.6 months, the overall median duration of response was 5.75 months and the median progression-free survival was 5.4 months.1
EV-201 Study: A Single-Arm, Open-Label, Multicenter Study of Enfortumab Vedotin for Treatment of Patients with Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Immune Checkpoint Inhibitor Therapy (Abstract #TPS4590, poster session on Saturday, June 2 from 8:00-11:30 a.m. CT)iii

In addition, the EV-201 trial in progress poster was presented at the meeting. EV-201 is an ongoing single-arm, single-agent pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with checkpoint inhibitor therapy, including those who had also been treated with a platinum chemotherapy and those who were platinum naive.3

More information about the enfortumab vedotin clinical trials can be found at View Source

About Urothelial Cancer
According to the American Cancer Society, urothelial cancer, also known as transitional cell carcinoma (TCC), is the most common type of bladder canceriv (90 percent of casesv). Approximately 81,000 people in the U.S. are anticipated to be diagnosed with bladder cancer during 2018.vi Bladder cancer is the fourth most common cancer in men, but is less common in women.6 Outcomes are poor for people diagnosed with metastatic disease, with a five-year survival rate of 4.8 percent.vii

About Enfortumab Vedotin
Enfortumab vedotin is an investigational ADC composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE, using Seattle Genetics’ proprietary, linker technology. Enfortumab vedotin targets Nectin-4, a cell adhesion molecule identified as an ADC target by Astellas, which is expressed on many solid tumors.