On June 1, 2019 Five Prime Therapeutics, Inc. (NASDAQ: FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported monotherapy data from the dose escalation portion of the Phase 1a/1b clinical trial of FPA150 in patients with advanced solid tumors (Press release, Five Prime Therapeutics, JUN 1, 2019, View Source [SID1234536770]). These data were presented at the Developmental Immunotherapy and Tumor Immunobiology Poster Session during the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The poster can be found on the Scientific Publications page of the Five Prime Therapeutics website.

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The data are the first presentation of FPA150 results and include safety and pharmacokinetics results from the Phase 1a monotherapy dose escalation portion of the study. The Phase 1a monotherapy portion of the study is being conducted in patients with advanced solid tumors, and the Phase 1b monotherapy expansion is enrolling patients with breast, ovarian and endometrial tumors that overexpress B7-H4.

"FPA150 is a first-in-class B7-H4 antibody that blocks inhibitory signaling to CD8 T cells and promotes the killing of B7-H4 overexpressing tumors through enhanced ADCC," said Jasgit Sachdev, M.D. and Director of Breast and Gynecologic Early Phase Trials at the HonorHealth Research Institute. "It is promising to see in this study that FPA150 was well tolerated at doses as high as 20mg/kg with no dose-limiting toxicities."

The open-label, multi-dose, multi-center Phase 1a dose escalation study was conducted in patients with advanced-stage solid tumors regardless of B7-H4 overexpression at monotherapy doses ranging from 0.01 to 20 mg/kg every three weeks in an accelerated titration followed by 3+3 design and in a separate dose exploration cohort in which patients with tumors that overexpress B7-H4 were treated at doses of 3 or 10 mg/kg every three weeks with mandatory pre- and on-treatment biopsies.

FPA150 monotherapy demonstrated a favorable safety profile with no dose-limiting toxicities or treatment-related serious adverse events. Evaluation of anti-tumor activity is ongoing. A recommended dose of 20 mg/kg every three weeks was selected based on safety and pharmacokinetics.

"Rapid enrollment of this first-in-human study of a novel targeted agent with checkpoint blockade and ADCC activity highlights the significant unmet need in patients with advanced breast and gynecologic cancers," said Helen Collins, Chief Medical Officer of Five Prime Therapeutics. "The preliminary data from the Phase 1a portion of this study, in patients with tumors overexpressing B7-H4, support continued evaluation of FPA150 in the monotherapy and in the anti-PD1 combination therapy setting."

Of the 29 patients in the Phase 1a portion of the study,18 had B7-H4 positive tumors based on medium or high immunohistochemistry (IHC) scores, including 11 patients with advanced ovarian cancer. Of these, one patient with ovarian cancer, who had been treated with seven prior lines of therapy including anti-PD1 therapy, achieved a confirmed partial response with a duration of 6.2 months.

Monotherapy Phase 1b expansion began in February 2019 and is enrolling cohorts of patients with B7-H4 positive breast, ovarian and endometrial cancers at a dose of 20 mg/kg every three weeks. A safety lead-in of the combination of Keytruda (pembrolizumab), a PD1 antibody, and FPA150 has also begun enrolling patients with B7-H4 positive ovarian cancer. The company expects to present preliminary efficacy results from the monotherapy expansion cohorts and early safety results from the FPA150-Keytruda combination at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) in September 2019.

About FPA150
FPA150 is a novel, fully human, afucosylated monoclonal antibody targeting B7-H4. B7-H4 overexpression is observed in multiple solid tumors, including breast and gynecologic cancers. FPA150 is designed with a dual mechanism of action: blocking the T cell checkpoint activity of B7-H4 as well as promoting enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells expressing B7-H4.

About Five Prime Therapeutics
Five Prime Therapeutics, Inc. discovers and develops innovative protein therapeutics to improve the lives of patients with serious diseases. Five Prime’s product candidates have innovative mechanisms of action and address patient populations in need of better therapies. The company focuses on researching and developing immuno-oncology and targeted cancer therapies paired with companion diagnostics to identify patients who are most likely to benefit from treatment with Five Prime’s product candidates. Five Prime has entered into strategic collaborations with leading global pharmaceutical companies and has promising product candidates in clinical and preclinical developm

On June 1, 2019 Nektar Therapeutics (Nasdaq: NKTR) reported that biomarker and clinical data from PIVOT-02 is being presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Meeting in Chicago, Illinois (Press release, Nektar Therapeutics, JUN 1, 2019, View Source [SID1234536786]).

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New baseline biomarker analyses and updated clinical study efficacy and safety results were shared in a presentation titled, "Baseline tumor-immune signatures associated with response to bempegaldesleukin (NKTR-214) and nivolumab" (Abstract #2623/Poster Board #267) by Michael Hurwitz, Ph.D., M.D. who serves as Assistant Professor of Medicine, Medical Oncology at Yale Cancer Center during the "Developmental Immunotherapy and Tumor Immunobiology" poster session on Saturday, June 1, 2019.

"The Stage IV melanoma patients enrolled in the ongoing PIVOT-02 study continue to experience both deepening and durability of response over time," said Jonathan Zalevsky, Ph.D., Chief Scientific Officer at Nektar Therapeutics. "This translated into a 34% rate of complete response at a 12-month follow-up for the 38 efficacy-evaluable patients in this cohort. Further, 42% of patients achieved a 100% reduction in target lesions. Finally, corresponding lymphocyte data highlight the benefit of replenishing and stimulating T cells continuously over the course of treatment with an I-O doublet regimen."

Bempegaldesleukin (NKTR-214, bempeg) is an investigational, CD122-preferential IL-2 pathway agonist designed to provide sustained signaling through the IL-2 beta-gamma receptor. PIVOT-02 is an ongoing Phase 2 study evaluating bempeg in combination with nivolumab in solid tumors.

Highlights from the biomarker, clinical efficacy and safety data presented at ASCO (Free ASCO Whitepaper) 2019 are provided below:

Biomarkers and Mechanism of Action:

Exploratory biomarker analyses of PIVOT-02 baseline tumor biopsies identified immune signatures that potentially enrich for response in patients with 1L metastatic melanoma and not 1L metastatic urothelial carcinoma.
Notable response rates were seen in both 1L metastatic melanoma and 1L metastatic urothelial cancer patients (ASCO 2019 and ASCO (Free ASCO Whitepaper)-GU 2019), regardless of PD-L1 status or unfavorable tumor microenvironments.
12 Month Follow-Up for 1L Melanoma Cohort in PIVOT-02:
(Response measured by RECIST 1.1 by independent central radiology review for 38 efficacy-evaluable patients per protocol which were treated at the recommended Phase 2 dose in PIVOT-02 and with >1 on treatment scan. Data cut as of March 29, 2019):

At a median time of follow-up of 12.7 months, confirmed objective response rate (ORR) was 53% (20/38) in efficacy-evaluable patients, with 34% (13/38) of patients achieving confirmed complete responses. 42% (16/38) of patients achieved a maximum reduction of 100% in target lesions. DCR, also known as disease control rate (CR+ PR + SD) was 74%.
Median time to response was 2 months. Median duration of response was not reached. At the 12.7 month median follow-up, data were too immature to calculate median progression-free survival (PFS).
80% (16/20) of patients with responses have ongoing responses. Amongst the 35 patients with known pre-treatment PD-L1 status, ORR in PD-L1 negative patients was 6/14 (43%) and in PD-L1 positive patients was 13/21 (62%). One of three patients with unknown PD-L1 baseline status experienced a CR.
The most common (>30%) treatment-related adverse events (TRAEs) were grade 1-2 fatigue (65.9%), pyrexia (61.0%), rash (56.1%), pruritus (48.8%), nausea (41.5%), influenza like illness (39.0%), arthralgia (36.6%), chills (34.1%) and myalgia (31.7%). A total of 6/41 (14.6%) of patients experienced a Grade 3 (G3) or higher TRAE with 4/41 (9.8%) patients discontinuing treatment due to a TRAE. A total of 41 patients have been treated at the RP2D with 3 patients discontinuing prior to 1st scan due to an unrelated treatment-emergent adverse event (n=1) and patient decision (n=2).
A Phase 3 trial evaluating bempeg in combination with nivolumab versus nivolumab in first-line advanced melanoma patients is currently recruiting patients (NCT03635983). A Phase 2 pivotal trial evaluating bempeg in combination with nivolumab in first-line metastatic urothelial cancer is currently recruiting patients (NCT03785925).

Details of the poster presentation are provided below and a link to a copy of the poster presentation is available on Nektar’s corporate website: View Source

Abstract #2623/Poster Board #267
Title: "Baseline tumor-immune signatures associated with response to bempegaldesleukin (NKTR-214) and nivolumab", Hurwitz, M., et al.
Date: Saturday, June 1, 2019, 8:00 a.m. – 11:00 a.m. Central Time
Location: McCormick Place, Exhibit Hall A

On June 1, 2019 Intensity Therapeutics, Inc., a clinical-stage biotechnology company pioneering a novel, immune-based approach to treat solid tumor cancers through direct injection of its proprietary therapeutic agents, reported positive preliminary results from the company’s ongoing Phase 1/2 clinical trial of its lead product candidate, INT230-6, in a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Intensity Therapeutics, JUN 1, 2019, View Source [SID1234536755]).
The poster highlights the results of 34 patients with 15 different types of advanced or metastatic solid tumors that have failed all or are not candidates for approved, available therapies.

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INT230-6 was well tolerated in doses up to 120 mL, including intratumoral dosing into more than 100 tumors deep in the body. The 120 mL dose of INT230-6 contains amounts of the cytotoxic agents greater than a typical intravenous (IV) dose. Based on comparisons to historical IV data of the active agents comprising INT230-6, the observed pharmacokinetic profiles indicate that drug remains mostly in the tumor following INT230-6 dosing. While the trial is aimed at assessing safety, several patients have shown tumor shrinkage and prolonged disease control after completing INT230-6 treatment. The results show greater benefit in patients who have received higher doses, and who have had multiple tumors injected. Dose escalation is ongoing.

Additionally, the immune activation data observed was consistent with nonclinical data, as local delivery of INT230-6 into tumors induced an immune response with increases of CD4+ and CD8+ T-cells in the blood and in the tumor microenvironment without any immune-related adverse events. Several patients have had shrinkage of non-injected tumors indicating an abscopal response.

"We are excited and encouraged by the positive preliminary results of our Phase 1/2 trial," said Lewis H. Bender, President and Chief Executive Officer of Intensity Therapeutics. "It is our aim to improve cancer treatment, reduce the side effects associated with systemic therapies and improve patient outcomes using intratumorally dosed INT230-6."

"The patients in our trial have a tremendous need for a new therapy. They have failed a median of three prior treatments with a number of patients having progressed following seven or more drug therapies," said Ian B. Walters, MD, Chief Medical Officer of Intensity Therapeutics. "Thus far, the data indicate that direct intratumoral injection of our product minimizes systemic side effects while promoting an augmented natural immune response that can fight a patient’s cancer for several months following completion of our treatment."

Details of the poster presentation are as follows:

Title: Safety profile of INT230-6, a novel intratumoral (IT) formulation, during injections into a variety of refractory deep and superficial tumors with evidence of tumor regression and immune activation

Abstract Number: 2602

Date/Time: Saturday, June 1, 2019, 8-11 a.m. CDT

Poster Session: Developmental Immunotherapy and Tumor Immunobiology

Presenter: Anthony El-Khoueiry, MD, Associate Professor of Clinical Medicine and Director of the Phase I Drug Development Clinical Program, University of Southern California

About INT230-6

INT230-6, Intensity’s lead proprietary product candidate, is designed for direct intratumoral injection. The drug is comprised of two proven, potent anti-cancer agents and a penetration enhancer molecule that helps disperse the drugs throughout tumors and diffuse into cancer cells. INT230-6 is being evaluated in a Phase 1/2 clinical study (NCT03058289) in patients with various advanced solid tumors. In preclinical studies, INT230-6 eradicated tumors by a combination of direct tumor kill and recruitment of dendritic cells to the tumor micro-environment that induced anti-cancer T-cell activation. Treatment with INT230-6 in in vivo models of severe cancer resulted in substantial improvement in overall survival compared to standard therapies. Further, INT230-6 provided complete responder animals with long-term, durable protection from multiple re-inoculations of the initial cancer and resistance to other cancers. In mouse models, INT230-6 has shown strong synergy with checkpoint blockage, including anti-PD-1 and anti-CTLA4 antibodies. INT230-6 was discovered from Intensity’s DfuseRxSM platform.

On June 1, 2019 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported results from the CDX-3379 clinical program at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Celldex Therapeutics, JUN 1, 2019, View Source [SID1234536771]). To date, three studies of CDX-3379 have enrolled patients with head and neck squamous cell carcinoma (HNSCC), including the ongoing Phase 2 exploratory study of CDX-3379 in combination with Erbitux (cetuximab) in patients with cetuximab-resistant, advanced human papillomavirus (HPV) negative HNSCC who have previously been treated with an anti-PD1 checkpoint inhibitor.

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Emerging data from the Phase 2 study and earlier studies of CDX-3379 suggest that antitumor activity may be associated with somatic mutations in certain genes. Based on these observations, Celldex conducted an exploratory biomarker analysis in 18 HNSCC patients across the CDX-3379 clinical development program. These results support the further development of CDX-3379 in biomarker-selected patient populations and were highlighted during a presentation at ASCO (Free ASCO Whitepaper) by Julie E. Bauman, MD, MPH, Professor of Medicine, Chief, Division of Hematology and Oncology, Associate Director, Translational Research, University of Arizona Cancer Center, lead author for the poster and an investigator in the Phase 2 study.

"We have observed intriguing clinical activity across a number of patients with similar gene mutation patterns in a disease that has extremely limited treatment options and a particularly poor prognosis," said Dr. Bauman. "While the data are early, they are provocative and suggest the potential for a biomarker enrichment strategy that could change the standard of care for these patients. I look forward to the opportunity to obtain additional data on CDX-3379 in biomarker selected patient populations."

CDX-3379 is a human monoclonal antibody that uniquely blocks the activity of ErbB3 (HER3). ErbB3 is expressed in many cancers, including head and neck squamous cell cancer (HNSCC) and is believed to be an important receptor regulating cancer cell growth and survival as well as resistance to targeted therapies.

Biomarker analysis

Next-generation sequencing was performed on tumor samples from 18 patients with HNSCC treated with CDX-3379 across the three clinical studies. This data set included four patients with clinical responses, including two durable complete responses (11+ months and 8.3 months), an exceptional partial response (greater than 92% tumor shrinkage) and an unconfirmed partial response; eight patients with stable disease and/or tumor shrinkage; and, six patients with progressive disease.

Across the CDX-3379 program, FAT1 and NOTCH1, NOTCH2, or NOTCH3 mutations and primary tumor site of oral cavity were associated with clinical activity (clinical response, tumor shrinkage and stable disease) in HNSCC
All four clinical responses occurred in patients with FAT1 mutations
All four clinical responses occurred in patients with a primary tumor site of oral cavity
Three of the four clinical responses occurred in patients who also had NOTCH1, NOTCH2 or NOTCH3 mutations
Also, of note, all patients (n=7 of 18) who experienced clinical benefit (objective response or stable disease greater than or equal to 12 weeks) had FAT1 and/or NOTCH1-3 mutations.
Current literature suggests that loss of FAT1 function results in activation of the transcriptional cofactor YAP11; YAP1 has been shown to upregulate components of ErbB signaling pathways2,3, including the ErbB3 ligand NRG14
Inactivating mutations in the FAT1 and NOTCH genes have been identified in 32% and 26% of HPV(-) HNSCC tumors, respectively5
Preclinical studies investigating the association of CDX-3379 sensitivity and inactivating mutations of FAT1 and other genes are ongoing

Phase 2 CDX-3379 Study Results and Next Steps

This multicenter, open-label, Phase 2 study of CDX-3379 in combination with cetuximab is designed to enroll approximately 30 patients with cetuximab-resistant, advanced, HPV negative HNSCC who have previously been treated with an anti-PD1 checkpoint inhibitor, a population with limited options and a particularly poor prognosis. Cetuximab is dosed weekly (initial dose at 400 mg/m2 IV, then 250 mg/m2 IV); CDX-3379 (12 mg/kg IV) is administered once every three weeks. Treatment continues until disease progression or intolerance, and assessments occur every six weeks. Using a Simon two-stage design, the first stage of study was designed to enroll 13 patients, and if at least one patient achieved a partial response or complete response, enrollment could progress to the second stage; this objective was met.

Fifteen patients were enrolled in stage 1 of the study. Patients had a median of 3 (range of 2-6) prior cancer therapy treatments. All patients had received prior checkpoint inhibitor treatment and 14 of 15 patients were cetuximab refractory. Notable clinical activity was observed in this refractory patient population where treatment options are limited.

A durable confirmed complete response (11+ months) was observed; this response remains ongoing and the patient continues to receive treatment.
An unconfirmed partial response (uPR) in a patient that had not received cetuximab was also observed.
7 patients experienced stable disease (47%; includes uPR).
A clinical benefit rate of 29% was achieved (objective response or stable disease greater than or equal to 12 weeks).
Dose reductions and/or delays to the combination therapy in the majority of patients may have impacted the magnitude of anti-tumor activity; dose modifications are being considered for future studies.
CDX-3379 in combination with cetuximab was generally associated with the expected target-mediated adverse events of diarrhea and rash.
Celldex intends to incorporate evaluation of biomarkers for patient selection into the CDX-3379 development program, either through amending the existing study or concluding the study and initiating a new clinical trial. The Company, working together with investigators and key opinion leaders in the treatment of HNSCC, anticipates finalizing these plans in the coming weeks.

Erbitux is a registered trademark of Eli Lilly & Co.
1Martin D, Nat Commun 2018. 2Zhang J, Nat Cell Biol 2009. 3Wang C, Cancer Res 2017. 4He C, Oncogene 2015. 5Cancer Genome Atlas Network, Nature 2015.

About CDX-3379
CDX-3379 is a human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody that selectively binds and inhibits ErbB3 activity. ErbB3 may be an important receptor regulating cancer cell growth and survival as well as resistance to targeted therapies, and it is expressed in many cancers, including head and neck, thyroid, breast, lung and gastric cancers, as well as melanoma. The proposed mechanism of action for CDX-3379 sets it apart from other drugs in development in this class due to its ability to block both ligand-independent and ligand-dependent ErbB3 signaling by binding to a unique epitope. It has a favorable pharmacologic profile, including a longer half-life and slower clearance relative to other drug candidates in this class. CDX-3379 also has potential to enhance anti-tumor activity and/or overcome resistance in combination with other targeted and cytotoxic therapies to directly kill tumor cells.

On June 1, 2019 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo), reported that new data from a pooled analysis of the phase 3 ENLIVEN study and phase 1 extension study showed continued treatment with pexidartinib resulted in an increased tumor response rate in TGCT patients (Press release, Daiichi Sankyo, JUN 1, 2019, https://www.prnewswire.com/news-releases/daiichi-sankyos-pexidartinib-demonstrated-further-improvement-with-continued-treatment-of-tenosynovial-giant-cell-tumor-patients-in-new-long-term-analysis-presented-at-2019-asco-annual-meeting-300860162.html [SID1234536787]). The data will be presented during a Poster Session on Saturday, June 1, at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Abstract #11042; 8:00-11:00 a.m. CDT).

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The long-term pooled results showed the best overall response with pexidartinib at a median treatment duration of 17 months was 54 percent by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and 64 percent by Tumor Volume Score (TVS). The median duration of response was not reached.

The safety profile of pexidartinib in the long-term follow-up was consistent with what has been seen in previous analyses. Across the studies, the most frequent adverse events were hair color change (75%), fatigue (60%), nausea (45%), arthralgia (38%), aspartate aminotransferase (AST) increase (30%) and diarrhea (30%). Pexidartinib was associated with two clinically distinct types of hepatic adverse reactions. The first was frequent dose-dependent aminotransferase elevations that may be a pharmacologic effect of CSF1R inhibition. The second hepatic adverse reaction was an idiosyncratic serious mixed or cholestatic hepatotoxicity. Across the pexidartinib clinical program, there were two irreversible cases of cholestatic liver injury, both in non-TGCT study populations. One patient died with advanced cancer and ongoing liver toxicity and one patient required a liver transplant.1

"Looking across the longer-term findings from both the pivotal phase 3 trial and phase 1 extension study, the results demonstrated continued and improved effect of pexidartinib in reducing tumor size in TGCT patients," said A.J. Gelderblom, MD, Chair of the Department of Medical Oncology at the Leiden University Medical Center and an ENLIVEN investigator. "This is important because TGCT is often a chronic disease, and we do not have effective treatment options for patients whose TGCT is inoperable or for which surgery would likely be associated with severe morbidity or functional limitations, like those enrolled in the studies."

Additional data published online ahead of ASCO (Free ASCO Whitepaper) (Abstract #e22527) further highlight the need for new treatment options, showing that TGCT patients missed more time from work due to disability and medical visits. The disability burden seen was greater in patients receiving surgery.

"We are pleased to share additional data that reinforce the potential of pexidartinib to offer clinically meaningful improvement for select patients with TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery," said Dale Shuster, Ph.D., Executive Director, Global Oncology R&D, Daiichi Sankyo. "We look forward to working with regulatory authorities and delivering on our goal to help address the significant unmet need that exists in the treatment of this rare and debilitating tumor."

About the Phase 1 Extension Study
Patients enrolled in this phase 1 single-arm, multi-center, extension cohort study included those with a histologically confirmed diagnosis of TGCT with demonstrated tumor progression within the past year that was recurrent, inoperable or resectable but requiring extensive surgery. Following baseline assessment, the efficacy of pexidartinib was assessed radiologically every two months utilizing RECIST 1.1 criteria and TVS. Patients remained on treatment until disease progression or drug intolerance.

Interim data from the phase 1 study were published in The New England Journal of Medicine.2

About the ENLIVEN Study
ENLIVEN, a double-blind, randomized, global multi-center, pivotal phase 3 study, evaluated pexidartinib in patients with symptomatic advanced TGCT for whom surgical removal of the tumor would be associated with potentially worsening functional limitation or severe morbidity. The first part of the study, the double-blind phase, enrolled 120 patients who were randomized (1:1) to receive either pexidartinib or placebo at 1000 mg/day for 2 weeks followed by 800 mg/day for 22 weeks in order to evaluate the efficacy and safety of pexidartinib versus placebo. The primary endpoint of the study was the percentage of patients achieving a complete or partial response after 24 weeks of treatment (Week 25), as assessed with centrally-read MRI scans using RECIST 1.1 criteria. Key secondary endpoints included range of motion, response by tumor volume score, PROMIS physical function, stiffness, and measures of pain reduction.

After completing the first part of the study, patients randomized to either pexidartinib or placebo were eligible to take part in the second part of ENLIVEN, a long-term, open-label part where patients could continue to receive or start to receive pexidartinib. In October 2016, following two reported cases of serious, non-fatal liver toxicity in the ENLIVEN study, the data monitoring committee (DMC) recommended that patients receiving placebo in the first part of the study should no longer be eligible to start pexidartinib in the second part of the study. A total of 120 patients who were enrolled prior to the DMC recommendation continued with the study according to the revised protocol.

About TGCT (PVNS/GCT-TS)
TGCT, also referred to as pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCT-TS), is a rare, nonmalignant tumor that can be locally aggressive. TGCT affects the synovium-lined joints, bursae and tendon sheaths, resulting in swelling, pain, stiffness and reduced mobility in the affected joint or limb.3, 4, 5

While the exact incidence of TGCT is not known, it is estimated that the incidence of TGCT is 11 to 50 cases per million person-years, based on studies from three countries.6, 7, 8 TGCT is subcategorized into two types: localized, which is more common and accounts for 90 percent of cases, and diffuse, which accounts for 10 percent of cases.7,8 The current standard of care for TGCT is surgical resection.3,4 However, in patients with a recurrent, difficult-to-treat or diffuse form where the tumor can wrap around bone, tendons, ligaments and other parts of the joint, it is more difficult to remove or might not be amenable to improvement with surgery due to the risk of morbidity and potential recurrence. Additional surgeries for more severe cases can lead to significant joint damage, debilitating functional impairments and reduced quality of life, and amputation may be considered.9, 10, 11

Recurrence rates for localized TGCT are estimated to be up to 15 percent following complete resection.4,12,13,14 Diffuse TGCT recurrence rates are estimated to be about 20 to 50 percent following complete resection.5,12,15 TGCT affects all age groups; the diffuse type, on average, occurs most often in people below the age of 40, and the localized type typically occurs in people between 30 and 50 years old. 3,6,7,8

About Pexidartinib
Pexidartinib is an investigational, novel, oral small molecule that potently inhibits the colony stimulating factor-1 receptor (CSF1R), which is a primary growth driver of abnormal cells in the synovium that cause TGCT. Pexidartinib also inhibits c-kit and FLT3-ITD. Pexidartinib was discovered by Plexxikon Inc., the small molecule structure-guided R&D center of Daiichi Sankyo.

Pexidartinib is currently under regulatory review with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of for adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. In addition to Priority Review designation, pexidartinib has been granted Breakthrough Therapy designation for the treatment of patients with pigmented villonodular synovitis (PVNS) or giant cell tumor of the tendon sheath (GCT-TS), where surgical resection may result in potentially worsening functional limitation or severe morbidity, and Orphan Drug designation for PVNS/GCT-TS by the FDA. Pexidartinib also has received Orphan Drug designation from the European Commission for the treatment of TGCT.

Pexidartinib is an investigational compound that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in pivotal stage development include: [fam-] trastuzumab deruxtecan, an antibody drug conjugate (ADC) for HER2 expressing breast, gastric and other cancers; quizartinib, an oral selective FLT3 inhibitor, for newly-diagnosed and relapsed/refractory FLT3-ITD acute myeloid leukemia (AML); and pexidartinib, an oral CSF1R inhibitor, for TGCT. For more information, please visit: www.DSCancerEnterprise.com.