On May 31, 2019 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development of novel products for serious rare and ultra-rare genetic diseases, reported that it will present at the following upcoming investor conferences (Press release, Ultragenyx Pharmaceutical, MAY 31, 2019, View Source [SID1234536730]):

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!

Shalini Sharp, the company’s Chief Financial Officer, will present at the Jefferies Healthcare Conference on Tuesday, June 4, 2019 at 8:00 a.m. ET in New York, NY.

Emil D. Kakkis, M.D., Ph.D., the company’s Chief Executive Officer, President and Founder, will present at the Goldman Sachs 40TH Annual Global Healthcare Conference on Thursday, June 13, 2019 at 9:20 a.m. PT in Palos Verdes, CA.
The live and archived webcast of the company presentations will be accessible from the company’s website at View Source The replay of the webcast will be available for 90 days.

On May 31, 2019 BerGenBio ASA (OSE:BGBIO), reported that it will share its latest updates and data on an investor call on 4 June 2019, during the annual American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting (Press release, BerGenBio, MAY 31, 2019, View Source [SID1234536747]). BerGenBio’s senior management team will be hosting the call at 15:30 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!

Dial-in details are:

Standard International Dial-In: +44 (0) 2071 928000
United States Dial-In: 16315107495
Participant Code: 4352428
The call will focus on two peer reviewed abstracts on Phase II clinical data with bemcentinib in the treatment of Non-Small Cell Lung Cancer and Acute Myeloid Leukemia.

On May 31, 2019 bluebird bio, Inc. (Nasdaq: BLUE) reported that the Company will hold a conference call to discuss data presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting on Friday, June 14 at 8:00 am ET (Press release, bluebird bio, MAY 31, 2019, View Source [SID1234536718]).

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!

In addition, members of the management team will present at the following upcoming investor conferences:

Jefferies 2019 Healthcare Conference, Tuesday, June 4, at 11:30 am ET at The Grand Hyatt, New York, NY
Goldman Sachs 40th Annual Healthcare Conference, Tuesday, June 11 at 10:00 am PT at the Terranea Resort, Rancho Palos Verdes, CA
To access the live webcasts of bluebird bio’s presentations, please visit the "Events & Presentations" page within the Investors & Media section of the bluebird bio website at View Source Replays of the webcasts will be available on the bluebird bio website for 90 days following the events.

On May 31, 2019 NantKwest (Nasdaq:NK), a leading clinical-stage, natural killer cell based therapeutics company, NantCell Inc., a privately held immunotherapy company, and NantOmics, a privately held molecular diagnostic company, reported that preclinical and clinical updates will be provided in four abstracts as part of the upcoming Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, IL, which runs from May 31st – June 4th, 2019 (Press release, NantKwest, MAY 31, 2019, https://ir.nantkwest.com/news-releases/news-release-details/nantkwest-nantcell-and-nantomics-provide-updated-preclinical-and?field_nir_news_date_value[min]=2019 [SID1234536734]).

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!

Dr. Patrick Soon-Shiong, Chairman and CEO of NantKwest, NantCell and NantOmics, commented, "Through a unique collaboration, combining the expertise of NantOmics’ multi-omics diagnostic capabilities with NantKwest’s and NantCell’s therapeutic capabilities, we are pleased to report for the first time the ability to comprehensively analyze a patient’s circulating cell-free RNA (cfRNA) and T Cell Receptor (TCR) repertoire and therapeutically intervene across a range of tumor types. We believe this type of fully integrated diagnostic and therapeutic intervention represent the next-generation in cancer care and shows real promise in improving response rates in comparison to traditionally single agent approaches. We look forward to transitioning these advances in medicine to the clinical care setting as quickly as possible."

Abstract Title: Innate and adaptive immunotherapy: An orchestration of immunogenic cell death by overcoming immune suppression and activating NK and T-cell therapy in patients with third line or greater Triple-Negative Breast Cancer (TNBC).

Sub-category: Triple-Negative

Category: Breast Cancer—Metastatic

Meeting: 2019 ASCO (Free ASCO Whitepaper) Annual Meeting

Abstract Number: e12566

Citation: J Clin Oncol 37, 2019 (suppl; abstr e12566)

Author(s):Chaitali Singh Nangia, Mira Kistler, Leonard S. Sender, John H. Lee, Frank R. Jones, Omid Jafari, Patrick Soon-Shiong; Chan Soon Shiong Institute for Medicine, Laguna Hills, CA; Chan Soon Shiong Institute of Medicine, El Segundo, CA; Children’s Hospital of Orange County, Laguna Hills, CA; Sanford Health, Sioux Falls, SD; Etubics Corporation, Seattle, WA; Medical Imaging Center of Southern California, Santa Monica, CA; NantKwest, Culver City, CA

Summary: Triple-negative breast cancer (TNBC) is a heterogenous subtype of breast cancer that is frequently aggressive and has limited treatment options. We hypothesize that effective and sustained response against TNBC requires a coordinated approach that: (1) reverses the immune-suppressive tumor microenvironment, (2) induces immunogenic tumor cell death and (3) Re-engages NK and T-cell tumor response against a cascade of tumor antigens. To test this hypothesis, we have developed a temporospatial approach that combines metronomic low dose chemotherapy, SBRT, off-the-shelf cryopreserved allogeneic NK cells, yeast and adenoviral tumor-associated antigen vaccines, an IL-15RαFc superagonist, and checkpoint inhibition. Methods: A phase 1b trial in patients with previously-treated metastatic TNBC was initiated. Treatment occurred in 3-week cycles of low-dose chemotherapy (aldoxorubicin, cyclophosphamide, cisplatin, nab-paclitaxel, 5-FU/L), antiangiogenic therapy (bevacizumab), SBRT, engineered allogeneic CD16 NK-92 cells (haNK), IL-15RαFc (N-803), adenoviral vector-based CEA, MUC1, brachyury, and HER2 vaccines, yeast vector-based Ras, brachyury and CEA vaccines, and an IgG1 PD-L1 inhibitor, avelumab. The primary endpoint is incidence of treatment-related adverse events (TRAEs). Secondary endpoints include ORR, DCR, PFS, and OS. Preliminary results reported on 8 subjects treated with 3rd-line or greater TNBC that have received at least 3 treatment cycles (mean = 6 cycles). All treatment was administered in an outpatient setting. All subjects had at least 1 grade ≥3 TRAE, primarily chemotherapy-related neutropenia. Grade ≥3 haNK-related AEs (fever and fatigue) were observed in 2 subjects. 2 subjects experienced SAEs. 7 subjects remain alive, with 6 subjects receiving ongoing study treatment. 1 CR (confirmed) and 2 PRs (one confirmed) have been observed to date. These preliminary data suggest that low-dose chemo-radiation combined with innate and adaptive immunotherapy can be administered safely in an outpatient setting with a manageable safety profile. Clinical trial information: NCT03387085.

Abstract Title: Innate and adaptive immunotherapy: An orchestration of immunogenic cell death by overcoming immune suppression and activating NK and T cell therapy in patients with third line or greater metastatic pancreatic cancer.

Sub-category: Pancreatic Cancer

Category: Gastrointestinal (Noncolorectal) Cancer

Meeting: 2019 ASCO (Free ASCO Whitepaper) Annual Meeting

Abstract Number: e15787

Citation: J Clin Oncol 37, 2019 (suppl; abstr e15787)

Author(s): Tara Elisabeth Seery, Mira Kistler, Leonard S. Sender, John H. Lee, Arvind Manohar Shinde, Anand Annamalai, Patrick Soon-Shiong; Chan Soon Shiong Institute for Medicine, Laguna Hills, CA; Chan Soon Shiong Institute of Medicine, El Segundo, CA; Chan Soon Shiong Institute for Medicine, El Segundo, CA; NantKwest, Culver City, CA; St. Vincent Medical Center, Los Angeles, CA; St. Vincent’s Medical Center, Los Angeles, CA

Summary:

Pancreatic cancer has multiple mechanisms to prevent immune recognition that lead to the creation of an immune suppressive tumor microenvironment. Our hypothesis is that sustained response against pancreatic cancer requires a coordinated approach that: (1) reverses the immune-suppressive tumor microenvironment, 2. induces immunogenic tumor cell death and (3) re-engages NK and T-cell tumor response against a cascade of tumor antigens. To test this hypothesis, we have developed a temporospatial approach that combines metronomic low-dose chemotherapy, SBRT, cryopreserved allogeneic NK cells, yeast and adenoviral tumor-associated antigen vaccines, an IL-15RαFc superagonist, and checkpoint inhibition. These preliminary data suggest that low-dose chemo-radiation combined with innate and adaptive immunotherapy can be administered safely in an outpatient setting.

Preliminary results of 12 subjects treated with 3rd-line or greater metastatic pancreatic cancer. All treatment was administered in an outpatient setting. AEs were primarily hematologic and managed by planned chemo dose reduction. Grade ≥3 TRAEs were observed in 9 out of 12 subjects, predominately chemotherapy-related neutropenia. 9 out of 12 subjects (75%) had a best response of stable disease (≥ 8 weeks). Median PFS is 7.1 months (4.4 – 8.8) and median OS is 8.2 months (5.7 – 9.7) with 1 subject continuing treatment

Preliminary Overall Survival of 8.2 months is encouraging for this heavily-pretreated population. Clinical trial information: NCT03586869.

Abstract Title: Correlation between circulating cell-free RNA biomarkers and response during combination immunotherapy in previously refractory metastatic TNBC patients.

Sub-category: Circulating Biomarkers

Category: Developmental Immunotherapy and Tumor Immunobiology

Meeting: 2019 ASCO (Free ASCO Whitepaper) Annual Meeting

Abstract No: e14027

Citation: J Clin Oncol 37, 2019 (suppl; abstr e14027)

Author(s):Chad Garner, Tara Elisabeth Seery, Chaitali Singh Nangia, John H. Lee, Liyang Huang, Leonard S. Sender, Shahrooz Rabizadeh, Patrick Soon-Shiong; NantHealth, Culver City, CA; Chan Soon Shiong Institute for Medicine, Laguna Hills, CA; NantKwest, Culver City, CA; Chan Soon-Shiong Institute for Medicine, El Segundo, CA; NantOmics, LLC, Culver City, CA; CSS Institute of Molecular Medicine, Culver City, CA.

Summary: A commercial liquid biopsy test was included as an exploratory component of an integrated immunotherapy clinical trial in previously refractory metastatic TNBC patients, combining innate, high-affinity natural killer cell (haNK) therapy with adenoviral and yeast-based vaccines and an IL-15 superagonist (NCT 03387085). The purpose of the study was to assess the utility of cell-free circulating RNA (cfRNA) as a predictor of treatment response. The amount and variability of cfRNA was found to be positively correlated with the tumor size. As cfRNA quantity and variability increased or decreased, a corresponding increase or decrease in tumor size was observed, respectively. Not all 18 genes showed consistent patterns of change across the six patients, however the average expression and variability of the 18 genes showed evidence of a correlation with tumor size change from baseline (p-values = 0.08 and 0.03, respectively). Only trace levels of PD-L1 expression were observed in all 6 patients at baseline, prior to the initiation of the combination immunotherapy. Among the 5 patients that showed a reduction in tumor size of at least 10%, 4 also showed an associated increase in cfRNA PD-L1 expression from nearly 0 to normalized values between 2.1 and 6.8. In an exploratory analysis in an ongoing combination immunotherapy clinical trial for TNBC showed that increasing and decreasing cfRNA levels are correlated with increasing and decreasing tumor size, respectively. Increased PD-L1 cfRNA levels are correlated with beneficial treatment response. Liquid biopsy of cfRNA could provide an effective biomarker of treatment response. Clinical trial information: NCT03387085.

Abstract Title: TCR repertoire analysis from peripheral blood for prognostic assessment of patients during treatment

Sub-category: Circulating Biomarkers

Category: Developmental Immunotherapy and Tumor Immunobiology

Meeting: 2019 ASCO (Free ASCO Whitepaper) Annual Meeting

Abstract Number: e14040

Citation:J Clin Oncol 37, 2019 (suppl; abstr e14040)

Author(s): Sadanand Vodala, Andrew Nguyen, Noe Rodriguez, Peter Sieling, Charles Joseph Vaske, Jon Van Lew, Kayvan Niazi, John H. Lee, Patrick Soon-Shiong, Shahrooz Rabizadeh; NantOmics, LLC, Culver City, CA; NantOmics, LLC, Santa Cruz, CA; NantBio, Inc, Culver City, CA; Sanford Health, Sioux Falls, SD; NantKwest, Culver City, CA

Summary:

Immune checkpoint inhibitor therapy offers substantial clinical advantage to a subset of patients but predictive/novel prognostic indicators are still scarce. T cell receptors (TCRs) play a crucial role in adaptive immunity and anti-tumor immune responses. Net diversity of TCR repertoires are altered in patients receiving immune checkpoint inhibitors. To study the prognostic significance of T cell repertoires as a biomarker of immune responses in cancer patients, TCR repertoires were characterized from peripheral blood using high throughput sequencing. Patients that show positive response had TCR clones that were stable, which may indicate an existing immune related response towards their tumor. TCR-targeted therapy potentially allows these existing T-cells to overcome blockade by tumor cells. Patients showing poor response show a TCR repertoire that is constantly changing potentially indicating that the tumor cells are not eliciting a strong T cell specific response. Further functional studies of T cell populations are planned to expand our understanding of T cell based immune therapies.

For additional information, please visit www.nantkwest, www.nantcell.com, and www.nantomics.

On May 31, 2019 The Janssen Pharmaceutical Companies of Johnson & Johnson reported findings from the investigational Phase 3 TITAN study, which showed the addition of ERLEADA (apalutamide) to androgen deprivation therapy (ADT) compared with placebo plus ADT significantly improved the dual primary endpoints of overall survival (OS) and radiographic progression-free survival (rPFS) in patients with metastatic castration-sensitive prostate cancer (mCSPC) (Press release, Johnson & Johnson, MAY 31, 2019, View Source [SID1234536735]).1 The study included patients with mCSPC regardless of extent of disease or prior docetaxel treatment history.1 Results were presented in an oral session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (abstract #5006), and simultaneously published online in The New England Journal of Medicine.The data were selected for the Best of ASCO (Free ASCO Whitepaper) 2019 Meetings, which highlight cutting-edge science and reflect leading research in oncology.

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!

ERLEADA plus ADT significantly extended OS compared to placebo plus ADT with a 33 percent reduction in the risk of death (HR=0.67; 95 percent CI, 0.51-0.89; P=0.0053).1 ERLEADA plus ADT also significantly improved rPFS compared to placebo plus ADT with a 52 percent reduction in risk of radiographic progression or death compared to placebo plus ADT (HR=0.48; 95 percent CI, 0.39-0.60; P<0.0001).1 The two-year OS rates, after a median follow-up of 22.7 months, were 82 percent for ERLEADA plus ADT compared to 74 percent for placebo plus ADT.1

These data formed the basis of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking approval of a new indication for ERLEADA for the treatment of patients with mCSPC, which is currently under review through the Real-Time Oncology Review (RTOR) program.

"Patients with metastatic castration-sensitive prostate cancer typically have a poor prognosis, with a median overall survival of less than five years. Despite advances in treatment, there is still a critical need to improve outcomes for these patients," said Dr. Kim Chi, Medical Oncologist at BC Cancer – Vancouver and principal investigator of the study. "These data suggest that apalutamide prolongs overall survival and delays disease progression in patients with metastatic castration-sensitive prostate cancer."

In addition to meeting the primary dual endpoints of OS and rPFS, the secondary endpoint of prolonged time to cytotoxic chemotherapy in patients treated with ERLEADA plus ADT was also met, with a 61 percent risk reduction compared with placebo plus ADT (HR=0.39; 95 percent CI, 0.27-0.56; P<0.0001).1 In exploratory endpoints, median time to PSA progression was more favorable following ERLEADA plus ADT, compared with placebo plus ADT, and prostate-specific antigen (PSA) reached undetectable levels in 68 percent of patients in the ERLEADA plus ADT arm and 29 percent of patients in the placebo plus ADT arm.1 Additionally, ERLEADA plus ADT, compared with placebo plus ADT, achieved a 34 percent risk reduction in median time to second progression-free survival (PFS2), defined as time from randomization to either disease progression on first subsequent anticancer therapy or death, whichever occurred first (HR=0.66; 95 percent CI, 0.50-0.87).1 Although time to pain progression was tested, it did not reach statistical significance. Due to a hierarchical statistical design, no formal testing for further secondary endpoints, including median time to chronic opioid use and median time to skeletal-related events, were conducted at this time.1

Adverse events were generally consistent with the known ERLEADA safety profile. The most common Grade 3/4 adverse events (AEs) for ERLEADA plus ADT, versus placebo plus ADT were similar (42 percent vs. 41 percent).1 The most common Grade 3 AEs for ERLEADA plus ADT versus placebo plus ADT were hypertension (8.4 percent vs. 9.1 percent) and skin rash (6.3 percent vs. 0.6 percent).1 Additional reported Grade 3 AEs for ERLEADA plus ADT versus placebo plus ADT were back pain (2.3 percent vs. 2.7 percent), blood alkaline phosphatase increased (0.4 percent vs. 2.5 percent) and anemia (1.7 percent vs. 3.2 percent).1 Treatment discontinuation due to AEs was 8 percent in the ERLEADA arm compared to 5 percent in the placebo arm.1 Rash of any grade was more common among patients treated with ERLEADA plus ADT, versus placebo plus ADT (27 percent vs. 9 percent, respectively).1

"The TITAN study results demonstrate that the addition of ERLEADA to ADT improves clinical outcomes without compromising health-related quality of life for a broad range of patients with metastatic castration-sensitive prostate cancer," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. "These data suggest that ADT alone should no longer be considered the standard of care for metastatic castration-sensitive prostate cancer and support Janssen’s investigation of ERLEADA in earlier stages of prostate cancer."

About the TITAN Study1
TITAN (NCT02489318) is a Phase 3 randomized, placebo-controlled, double-blind study in men with mCSPC regardless of extent of disease or prior docetaxel treatment history. The study included 1,052 patients included in intention-to-treat (ITT) population in 23 countries across 260 sites in North America, Latin America, South America, Europe and Asia Pacific. Patients with mCSPC were randomized 1:1 and received either ERLEADA (240 mg) plus continuous ADT (n=525), or placebo plus ADT (n=527). The recruitment period for the study spanned from December 2015 to July 2017. The study included mCSPC patients with both low- and high-volume disease, those who were newly diagnosed, or those who had received prior definitive local therapy or prior treatment with up to six cycles of docetaxel or up to six months of ADT for mCSPC. Participants were treated until disease progression or the occurrence of unacceptable treatment-related toxicity. An Independent Data-Monitoring Committee was commissioned by the sponsor to monitor safety and efficacy before unblinding and to make study conduct recommendations. Dual primary endpoints of the study were OS and rPFS. Secondary endpoints included time to cytotoxic chemotherapy, time to pain progression, time to chronic opioid use and time to skeletal-related event. Exploratory endpoints included time to PSA progression, time to PFS2 and time to symptomatic progression.1 For additional study information, visit ClinicalTrials.gov.

About Metastatic Castration-Sensitive Prostate Cancer
Metastatic castration-sensitive prostate cancer (mCSPC) refers to prostate cancer that still responds to ADT and has spread to other parts of the body.2,3 Patients with mCSPC tend to have a poor prognosis, with a median OS of less than five years, underscoring the need for new treatment options.2,3,4

About ERLEADA
ERLEADA (apalutamide) is an androgen receptor (AR) inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC). It became the first treatment to receive FDA approval for nmCRPC on February 14, 2018.5 The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer include apalutamide as a treatment option for patients with non-metastatic (M0) CRPC with a category 1 recommendation for those with a PSA doubling time ≤10 months*.6 Additionally, the American Urological Association (AUA) Guidelines for Castration-Resistant Prostate Cancer (CRPC) were updated to include apalutamide (ERLEADA) with continued ADT as a treatment option that clinicians should offer to patients with asymptomatic nmCRPC. It is included as one of the options clinicians should offer to patients with nmCRPC who are at high risk for developing metastatic disease (Standard; Evidence Level Grade A)**.7

*Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer V.2.2019. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed April 23, 2019. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application, and disclaims any responsibility for their application or use in any way.

**Standard: Directive statement that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be taken based on Grade A or B evidence.

**Evidence Level: A designation indicating the certainty of the results as high, moderate, or low (A, B, or C, respectively) based on AUA nomenclature and methodology.

ERLEADA IMPORTANT SAFETY INFORMATION5

CONTRAINDICATIONS

Pregnancy — ERLEADA (apalutamide) can cause fetal harm and potential loss of pregnancy.

WARNINGS AND PRECAUTIONS

Falls and Fractures — In a randomized study (SPARTAN), falls and fractures occurred in 16% and 12% of patients treated with ERLEADA compared to 9% and 7% treated with placebo, respectively. Falls were not associated with loss of consciousness or seizure. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone targeted agents.

Seizure — In a randomized study (SPARTAN), 2 patients (0.2%) treated with ERLEADA experienced a seizure. Permanently discontinue ERLEADA in patients who develop a seizure during treatment. It is unknown whether anti-epileptic medications will prevent seizures with ERLEADA. Advise patients of the risk of developing a seizure while receiving ERLEADA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others.

ADVERSE REACTIONS

Adverse Reactions — The most common adverse reactions (≥10%) were fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.

Laboratory Abnormalities — All Grades (Grade 3-4)

Hematology — anemia ERLEADA 70% (0.4%), placebo 64% (0.5%); leukopenia ERLEADA 47% (0.3%), placebo 29% (0%); lymphopenia ERLEADA 41% (2%), placebo 21% (2%)

Chemistry — hypercholesterolemia ERLEADA 76% (0.1%), placebo 46% (0%); hyperglycemia ERLEADA 70% (2%), placebo 59% (1%); hypertriglyceridemia ERLEADA 67% (2%), placebo 49% (0.8%); hyperkalemia ERLEADA 32% (2%), placebo 22% (0.5%)
Rash — Rash was most commonly described as macular or maculo-papular. Adverse reactions were 24% with ERLEADA versus 6% with placebo. Grade 3 rashes (defined as covering > 30% body surface area [BSA]) were reported with ERLEADA treatment (5%) versus placebo (0.3%).

The onset of rash occurred at a median of 82 days. Rash resolved in 81% of patients within a median of 60 days (range: 2 to 709 days) from onset of rash. Four percent of patients treated with ERLEADA received systemic corticosteroids. Rash recurred in approximately half of patients who were re-challenged with ERLEADA.

Hypothyroidism was reported for 8% of patients treated with ERLEADA and 2% of patients treated with placebo based on assessments of thyroid-stimulating hormone (TSH) every 4 months. Elevated TSH occurred in 25% of patients treated with ERLEADA and 7% of patients treated with placebo. The median onset was day 113. There were no Grade 3 or 4 adverse reactions. Thyroid replacement therapy, when clinically indicated, should be initiated or dose-adjusted.

DRUG INTERACTIONS

Effect of Other Drugs on ERLEADA — Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady-state exposure of the active moieties. No initial dose adjustment is necessary; however, reduce the ERLEADA dose based on tolerability [see Dosage and Administration (2.2)].

Effect of ERLEADA on Other Drugs — ERLEADA is a strong inducer of CYP3A4 and CYP2C19, and a weak inducer of CYP2C9 in humans. Concomitant use of ERLEADA with medications that are primarily metabolized by CYP3A4, CYP2C19, or CYP2C9 can result in lower exposure to these medications. Substitution for these medications is recommended when possible or evaluate for loss of activity if medication is continued. Concomitant administration of ERLEADA with medications that are substrates of UDP-glucuronosyl transferase (UGT) can result in decreased exposure. Use caution if substrates of UGT must be co-administered with ERLEADA and evaluate for loss of activity.

P-gp, BCRP or OATP1B1 substrates — Apalutamide is a weak inducer of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide 1B1 (OATP1B1) clinically. Concomitant use of ERLEADA with medications that are substrates of P-gp, BCRP, or OATP1B1 can result in lower exposure of these medications. Use caution if substrates of P-gp, BCRP or OATP1B1 must be co-administered with ERLEADA and evaluate for loss of activity if medication is continued.