On June 23, 2017 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported updated clinical data from the ongoing Phase 2b Selinexor Against Diffuse Aggressive Lymphoma (SADAL) study evaluating lead product candidate, selinexor (KPT-330), an oral Selective Inhibitor of Nuclear Export / SINE compound, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Press release, Karyopharm, JUN 23, 2017, View Source [SID1234519665]). The data will be featured in an oral presentation at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) taking place June 22-25, 2017 in Madrid, Spain. In the SADAL study, selinexor has achieved a 33.3% overall response rate (ORR) in patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for transplantation. The observed responses continue to be durable, with a median duration of response (DOR) of greater than 7 months, including prolonged complete responses (CRs).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Updated Phase 2b SADAL Data in Relapsed or Refractory DLBCL

In the oral presentation, titled "Single Agent Oral Selinexor Exhibits Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) of Both GCB and Non-GCB Subtypes: The Phase 2b SADAL Study," Marie Maerevoet, MD, Institute Jules Bordet in Belgium, will present the updated Phase 2b SADAL data. Per the SADAL study protocol, the updated efficacy data were restricted to the interim analysis cohort (n=63), which were previously reported at AACR (Free AACR Whitepaper) 2017, and the updated safety results include updated data on all patients that received at least one dose of selinexor as of the data cutoff date.

Dr. Maerevoet commented, "We are highly encouraged by the impressive response rates that continue to be observed with single-agent oral selinexor in these heavily pretreated patients with DLBCL who have received two or more prior therapies and are not eligible for transplantation, and for whom no standard therapy exists. Along with being clinically active and durable, including prolonged complete responses, the 60mg dose continues to be well tolerated with a low incidence of Grade 3 or greater adverse events, which were manageable with dose modifications and standard supportive care."

A summary of the efficacy data to be presented at EHA (Free EHA Whitepaper) 2017 is outlined in the following table and described below.

Best Responses* in Patients as of 15 May 2017

Category N ORR (%) CR (%) PR (%) SD (%) PD/NE (%)
All patients 63 21 (33.3%) 9 (14.3%) 12 (19.0%) 6 (9.5%) 36 (57.1%)

60 mg 32 11 (34.4%) 4 (12.5%) 7 (21.9%) 1 (3.1%) 20 (62.5%)
100 mg 31 10 (32.2%) 5 (16.1%) 5 (16.1%) 5 (16.1%) 16 (51.6%)

GCB-Subtype 32 9 (28.1%) 4 (12.5%) 5 (15.6%) 3 (9.4%) 20 (62.5%)
Non-GCB-Subtype 31 12 (38.7%) 5 (16.1%) 7 (22.6%) 3 (9.7%) 16 (51.6%)
*Responses were adjudicated according to the Lugano Classification (Cheson, 2014) by an independent central radiological review committee. ORR=Overall Response Rate (CR+PR), DCR=Disease Control Rate (CR+PR+SD), CR=Complete Response, PR=Partial Response, SD=Stable Disease, PD=Progressive Disease, NE=Not Evaluable for Response. Responses are based on interim unaudited data for the first 63 patients (of 90 total patients enrolled as of the data cutoff date).

Based on the modified intention-to-treat analysis of the first 63 patients (median of 3 prior treatment regimens (range 2-5)), as adjudicated by an independent central radiological committee, 21 patients responded (9 patients with a CR and 12 patients with a PR) for an ORR 33.3%. An additional 6 patients experienced SD, for a disease control rate of 42.9%. The median DOR across all patients was greater than 7 months and responses tended to occur rapidly with a median of 2 months to onset. Among patients who responded, the median time on treatment was 9 months with a follow up of 12.8 months. As of the data cutoff date, 9 patients who responded remained on treatment, including 6 patients with a CR.

The median overall survival was 8 months for all patients on the study, consistent with the 6-7 month published survival data in this population, indicating that their prognosis is extremely poor. As of the data cutoff date, median survival for the patients with PR or CR had not been reached and is over 9 months; the median survival for patients with SD or PD, NE disease was 4.8 months.

Selinexor also showed robust, single-agent activity against GCB and non-GCB subtypes of DLBCL: Of the 32 patients with DLBCL of the GCB-subtype, 9 responded (4 patients with a CR, 5 patients with a PR) for an ORR of 28.1%. Of the 31 patients with DLBCL of the non-GCB (or ABC)-subtype, 12 responded (5 patients with a CR, 7 patients with a PR) for an ORR of 38.7%. Finally, amongst the 14 patients with "double-" or "triple-hit" DLBCLs, the ORR was 35%, indicating that selinexor has clear activity in this population, which usually has a particularly poor prognosis.

Among the 90 patients evaluated for safety as of the data cutoff date, the most common adverse events (AEs) across both dosing groups were fatigue (61%), nausea (51%), thrombocytopenia (50%), anorexia (49%), vomiting (31%) and anemia (30%), and were primarily grades 1 and 2 and were managed with dose modifications and/or standard supportive care. As expected, the most common grade 3 and 4 AEs in the 60mg arm were thrombocytopenia (28%), neutropenia (17%), anemia (15%), and fatigue (11%) and were manageable with dose modifications and/or standard supportive care.

As previously announced, in consultation with the U.S. Food and Drug Administration (FDA), Karyopharm has amended the SADAL study protocol to become a single-arm study focusing solely on single-agent selinexor dosed at 60mg twice weekly and has eliminated the 100mg arm. The FDA has agreed that the single-arm trial design appears appropriate for accelerated approval in DLBCL, though eligibility for accelerated approval will depend on the complete trial results and available therapies at the time of regulatory action. In total, the SADAL study is expected to enroll up to a total of 130 patients in the 60mg single-arm cohort and Karyopharm plans to report top-line results in the second half of 2018.

"The IRC-confirmed durable responses achieved with single-agent oral selinexor have improved over time and continue to demonstrate robust single-agent activity and prolonged responses in patients with heavily pretreated DLBCL, and these responses correlate with improved overall survival," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We were particularly pleased to see a 35% response rate in the double- or triple-hit subgroup, a particularly difficult to treat patient population. The 60mg treatment arm is enrolling on track, and we look forward to reporting top-line data from the SADAL study in the second half of 2018. Assuming a positive outcome, we expect to seek accelerated approval for selinexor in DLBCL."

Details for the Oral Presentation at EHA (Free EHA Whitepaper) 2017:

Title: Single Agent Oral Selinexor Exhibits Durable Responses in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) of Both GCB and Non-GCB Subtypes: The Phase 2b SADAL Study
Presenter: Marie Maerevoet, Institute Jules Bordet, Brussels, Belgium
Abstract code: S469
Topic: Aggressive Non-Hodgkin lymphoma — Clinical
Session: Aggressive Non-Hodgkin lymphoma — Relapsed/refractory
Location: Hall C
Date and Time: Saturday, June 24, 2017 from 14:45 – 17:00 CET

About Selinexor

Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,000 patients have been treated with selinexor and it is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the Company’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

On June 23, 2017 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported data from its ongoing multicenter BP-004 trial of BPX-501 and rimiducid in a cohort of pediatric patients with acute leukemias who lack a matched donor (Press release, Bellicum Pharmaceuticals, JUN 23, 2017, View Source [SID1234519662]). Results from 47 patients demonstrated that administering BPX-501 following an alpha/beta T-cell depleted haploidentical hematopoietic stem cell transplant (alpha/beta T-cell depleted haplo-HSCT) produced rapid immune reconstitution, low incidence of acute and chronic Graft versus Host Disease (GvHD), and a low rate of disease relapse. The data will be reviewed in an oral presentation at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) at 5 p.m. CEST on June 24 in Madrid, Spain.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These data demonstrate that BPX-501-modified T cells can provide rapid hematological reconstitution and a potentially stronger anti-leukemic effect in children with high-risk disease than traditional T-cell depleted transplants," said Franco Locatelli, MD, PhD, Director of the Department of Hematology and Oncology at Ospedale Pediatrico Bambino Gesù in Rome, Italy. "The incidence of GvHD was low, and managed by standard treatments or the administration of rimiducid. Patients who received rimiducid experienced a recovery of the beneficial, non-reactive BPX-501 T cells. These are very encouraging early outcome results for children who need a stem cell transplant and lack a matched donor."

Summary of Results (Abstract S495)

Investigators evaluated the safety and efficacy of an infusion of BPX-501 in children with high-risk acute lymphoblastic leukemia (ALL) (n=28) and acute myeloid leukemia (AML) (n=19) following an alpha/beta T-cell depleted haplo-HSCT. Patients had a median follow-up of approximately eight months (11 months in surviving patients). Results from the three European trial sites showed:

Disease relapse rate of 14.72% in BPX-501 treated patients
Median neutrophil recovery = 16 days (9-24); median platelet engraftment = 11 days (8-19); median time to hospital discharge = 21.5 days (14-103)
Acute GvHD Grade 2-4 was 11.83%; acute GvHD Grade 3-4 was 4.70%
Chronic GvHD Grade Moderate-Severe was 3.23%
Non-relapse mortality (NRM) of 3.23% in BPX-501 patients
Re-expansion of infection-fighting BPX-501 cells after a sharp decrease following infusion of rimiducid, with no reoccurrence of GvHD
Results compare favorably to historic controls1
Commented Rick Fair, President and CEO of Bellicum Pharmaceuticals, "We are pleased by the profile observed with BPX-501 in pediatric patients receiving a haploidentical transplant, and by its potential to reduce disease relapse. These results provide important insights into the potential long-term benefits of BPX-501, and support our plans to begin a mid-stage study this year in adults with hematologic cancers, for whom lack of a matched donor and disease relapse are significant treatment challenges."

The presentation slides (abstract S495) will be made available in the Events and Presentations section of the Bellicum website shortly after the time of the presentation.

About BPX-501
BPX-501 is an adjunct T-cell therapy administered after allogeneic HSCT, comprising genetically modified donor T cells incorporating Bellicum’s CaspaCIDe safety switch. It is designed to provide a safety net to eliminate alloreactive BPX-501 T cells (via administration of activator agent rimiducid) should uncontrollable GvHD occur. This enables physicians to more safely perform stem cell transplants by administering BPX-501 engineered T cells to speed immune reconstitution, provide control over viral infections and enhance Graft-versus-leukemic effect, without unacceptable GvHD risk. The ongoing BP-004 clinical study of BPX-501 is being conducted at transplant centers in the U.S. and Europe.

On June 23, 2017 NewLink Genetics Corporation (NASDAQ:NLNK) reported the presentation of data from the Phase 1b portion of a study of indoximod, an IDO pathway inhibitor, in combination with idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia (AML) (Press release, NewLink Genetics, JUN 23, 2017, View Source [SID1234519660]). Abstract E-912, Indoximod in Combination with Idarubicin and Cytarabine for Upfront Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia (AML): Phase 1 Report, is being presented by Ashkan Emadi, M.D., Ph.D., Associate Professor of Medicine at the University of Maryland Greenebaum Comprehensive Cancer Center, during the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in Madrid, Spain on Friday, June 23, 2017, 9:30 AM to Saturday, June 24, 7:00 PM CET.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

These data indicate indoximod does not appear to add significant toxicity to standard therapy for patients with newly diagnosed AML, and no regimen-limiting toxicities (RLT) have been observed to date. Initial data show that the morphological complete remission (CR) rate is as expected after one cycle of induction chemotherapy. Seven of seven patients who achieved CR were found to have no minimal residual disease (MRD-neg).

"While from a small number of patients, these data show an encouraging MRD negativity rate and may offer the potential for measurable clinical benefits for patients," said Dr. Emadi, Principal Investigator of this study.

About Indoximod
Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is one of the key immuno-oncology targets involved in regulating the tumor microenvironment and immune escape.

On June 23, 2017 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported that results will be presented today from its global BP-004 clinical trial of BPX-501 in the Presidential Symposium at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) being held in Madrid, Spain (Press release, Bellicum Pharmaceuticals, JUN 23, 2017, View Source [SID1234519659]). Clinical results reported in pediatric patients with a wide range of genetic blood diseases and hematologic cancers suggest that BPX-501 lowers the risks associated with haploidentical stem cell transplants, increasing their acceptability for more patients who could benefit but lack a matched donor. The EHA (Free EHA Whitepaper)’s Presidential Symposium showcases the top abstracts selected by the Scientific Program Committee each year.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The vast majority of patients in this study experienced successful engraftment, no or low grade GvHD, rapid immune recovery and early hospital discharge," said Dr. Franco Locatelli, MD, PhD, Director of the Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù (OPBG), Rome. "All cases of uncontrolled acute GvHD were resolved by administration of rimiducid to activate the CaspaCIDe safety switch incorporated in BPX-501. With low incidence of transplant-related mortality and manageable GvHD, these data suggest that the addition of BPX-501 T cells could represent a meaningful advance for patients in need of a transplant but who lack a matched related donor."

Updated Results of BP-004 Study in Global and EU Populations

Investigators reported on pediatric patients with hematologic cancers and genetic blood diseases who underwent treatment with BPX-501 after an alpha/beta T-cell depleted haploidentical hematopoietic stem cell transplant (alpha/beta T-cell depleted haplo-HSCT) and had at least six months of follow-up. Investigators reviewed overall data on 98 patients from 12 centers in the U.S. and Europe, as well as on the subset of 61 patients at European sites.

At the 180-day measurement time point, cumulative incidence of transplant-related mortality (TRM) was 5% in the overall patient population. A significant reduction in viral infections and reinfections was observed with BPX-501 compared to results from a study in Rome (OPBG) in patients undergoing an alpha/beta T-cell depleted haplo-HSCT without the addition of BPX-501 (n=107). Additionally, there were no reported adverse events associated with the use of BPX-501 or rimiducid. At six months of follow-up, the cumulative incidence of Grade 2-4 acute Graft versus Host Disease (GvHD) was 13 percent. The cumulative incidence of chronic GvHD was three percent at one year of follow-up.

The administration of rimiducid was required in 11 patients with acute GvHD who did not respond to standard treatments. In all 11 cases, rimiducid rapidly resolved the GvHD. In addition, the non-reactive T cells recovered, with no recurrence of GvHD.

Data from the subset of 61 patients from European sites were also reviewed in the presentation. At six months of follow-up there was no transplant-related mortality. Cumulative GvHD incidence remains low, with incidence rates of 10 percent for Grade 2-4 acute GvHD, and three percent for Grade 3-4 acute GvHD. There was no persistent chronic GvHD.

"Data from our global BP-004 study continue to show consistent and strong overall outcomes across a wide range of diseases, suggesting the potential to enable curative stem cell transplants from partially matched donors for more children," said Rick Fair, President and CEO of Bellicum Pharmaceuticals. "Data from this ongoing BP-004 study in Europe, along with comparative data from an observational trial of pediatric patients undergoing a stem cell transplant from matched unrelated donors, are expected to support the filing of a European Marketing Authorization Application in mid-2018."

Patient Populations Included in Study, By Disease Type

Genetic Blood Diseases (n=59) Hematologic Cancers (n=39)
Primary immune deficiencies (n=26) Acute lymphoblastic leukemia (ALL) (n=21)
Thalassemia major (n=8) Acute myeloid leukemia (AML) (n=14)
Hemophagocytic lymphohistiocytosis (HLH) (n=6) Other (n=4)
Sickle cell disease (n=5)
Other (n=14)

Hemoglobinopathies and Erythroid Disorders Poster Presentation
Also today at the 22nd Congress of EHA (Free EHA Whitepaper), updated results will be presented in patients with hemoglobinopathies and erythroid disorders, including five patients with sickle cell disease, in a poster presentation titled: "The Use of BPX-501 Donor T-Cell Infusion (with Inducible Caspase 9 Suicide Gene) Together with HLA-Haploidentical Stem Cell Transplant to Treat Children with Hemoglobinopathies and Erythroid Disorders."

All 15 patients in the cohort showed normal hemoglobin levels and remained transfusion-free at 180 days, with no transplant-related mortality.

The Presidential Symposium oral presentation (abstract S146) will take place today, June 23 at 3:45 – 4:00 PM CEST (9:45-10:00 AM EDT) and the poster (abstract P381) will be reviewed today at 5:15 – 6:45 PM CEST (11:15 AM – 12:45 PM EDT). Both presentations will be made available in the Events and Presentations section of the Bellicum website shortly after the time of the respective presentation.

About BPX-501
BPX-501 is an adjunct T-cell therapy administered after allogeneic HSCT, comprising genetically modified donor T cells incorporating Bellicum’s CaspaCIDe safety switch. It is designed to provide a safety net to eliminate alloreactive BPX-501 T cells (via administration of activator agent rimiducid) should uncontrollable GvHD occur. This enables physicians to more safely perform stem cell transplants by administering BPX-501 engineered T cells to speed immune reconstitution, provide control over viral infections and enhance Graft-versus-leukemia effect, without unacceptable GvHD risk. The ongoing BP-004 clinical study of BPX-501 is being conducted at transplant centers in the U.S. and Europe.

On June 23, 2017 Bayer reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended regorafenib for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with Nexavar (sorafenib) (Press release, Bayer, JUN 23, 2017, View Source [SID1234519658]). Regorafenib is the first and only treatment that has demonstrated a significant improvement in overall survival in second-line HCC patients who previously had no other options. The final decision of the European Commission on the marketing authorization is expected in the coming months. The anti-cancer medication from Bayer is already approved under the brand name Stivarga in more than 90 countries worldwide for the treatment of metastatic colorectal cancer (CRC), including countries of the EU, and in more than 80 countries globally for the treatment of metastatic gastrointestinal stromal tumors (GIST), including countries of the EU. The product recently gained approval in the U.S. for second-line treatment of HCC and additional regulatory filings for Stivarga in HCC are under review in countries around the world, including China.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Liver cancer is one of the leading cancer-related causes of death in Europe. Nexavar, as the first and only approved systemic treatment for HCC, has been a major advance in this field, but effective second-line treatment options are urgently needed for patients," said Robert LaCaze, Executive Vice President and Head of the Oncology Strategic Business Unit at Bayer. "The positive opinion for regorafenib in Europe is great news for patients as it supports our efforts to make this treatment available to as many patients as possible in the second-line HCC setting and offers a treatment plan with two therapies that both have shown to improve overall survival."

Liver cancer is often more difficult to treat than other cancers with an annual mortality rate of 48,000 in in the EU. Globally, it is the second leading cause of cancer-related deaths.

The positive opinion is based on data from the international, multicenter, placebo-controlled Phase III RESORCE [REgorafenib after SORafenib in patients with hepatoCEllular carcinoma; NCT 01774344] trial, which investigated patients with HCC whose disease had progressed during treatment with Nexavar. In the trial, regorafenib plus best supportive care (BSC) was shown to provide a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo plus BSC (HR 0.63; 95% CI 0.50-0.79; p<0.0001), which translates to a 37% reduction in the risk of death over the trial period. The median OS was 10.6 vs. 7.8 months for regorafenib and the placebo groups, respectively. Adverse events observed in the trial were generally consistent with the known safety profile of regorafenib. The most common treatment-emergent adverse events (regorafenib vs. placebo group) were hand–foot skin reaction (53% vs. 8%), diarrhea (41% vs. 15%), fatigue (40% vs. 32%) and hypertension (31% vs. 6%).

About Hepatocellular Carcinoma
Hepatocellular carcinoma, or HCC, is the most common form of liver cancer representing approximately 70-85 percent of liver cancer worldwide. Liver cancer is the sixth most common cancer in the world and the second leading cause of cancer-related deaths globally. More than 780,000 cases of liver cancer are diagnosed worldwide each year (52,000 in the European Union, 501,000 in the Western Pacific region and 30,000 in the United States) and the incidence rate is increasing. In 2012, approximately 746,000 people died of liver cancer including approximately 48,000 in the European Union, 477,000 in the Western Pacific region and 24,000 in the United States.

About Regorafenib (Stivarga)
Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R).

Regorafenib is approved under the brand name Stivarga in more than 90 countries worldwide, including the U.S., countries of the EU, China and Japan for the treatment of metastatic colorectal cancer (mCRC). The product is also approved in over 80 countries, including the U.S., countries of the EU, China and Japan, for the treatment of metastatic gastrointestinal stromal tumors (GIST). It was recently approved in the U.S. for second-line treatment of HCC. Additional regulatory filings for Stivarga in HCC are under review in countries around the world, including China.

In the EU, Stivarga is indicated for the treatment of adult patients with mCRC who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy, as well as for the treatment of adult patients with unresectable or metastatic GIST who progressed on or are intolerant to prior treatment with imatinib and sunitinib.

Regorafenib is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx, now an Amgen subsidiary, under which Onyx receives a royalty on all global net sales of regorafenib in oncology.