1stOncology™: Cancer Intelligence Service – Page 13813 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Oncopeptides Announces Melflufen Data Accepted for Presentation at 2019 ASCO Annual Meeting

On May 15, 2019 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported that data from its Phase 1/2 O-12-M1 study evaluating melflufen, a lipophilic peptide-conjugated alkylator belonging to the novel class of peptidase enhanced cytotoxics, in the treatment of relapsed/refractory multiple myeloma (RRMM) have been selected for poster presentation at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place May 31 – June 4 in Chicago (Press release, Oncopeptides, MAY 15, 2019, View Source [SID1234536385]).

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 data offers an analysis of time to next treatment (TTNT) in patients with RRMM who were treated with melflufen and dexamethasone in the Phase 1/2 clinical study named O-12-M1. TTNT is used in Real World Evidence to assist treatment decisions and support economic reimbursement modeling.

"The acceptance of melflufen data for presentation on the global stage that the ASCO (Free ASCO Whitepaper) Annual Meeting affords serves as a positive and meaningful validation of the scientific rigor behind our melflufen clinical development program. The early-stage clinical data being presented offer insights into the potential clinical application and utilization of melflufen, which is also being studied now in the global, Phase 3 OCEAN trial" said Jakob Lindberg, CEO of Oncopeptides.

The full 2019 ASCO (Free ASCO Whitepaper) Annual Meeting abstract book can be found at: View Source

The abstract can be found on the company webpage under:
www.oncopeptides.com / Investors & Media / Presentations / Abstract ASCO (Free ASCO Whitepaper)

Analysis of time to next treatment (TTNT) in melflufen and dexamethasone-treated patients (pts) with relapsed/refractory multiple myeloma (RRMM).
Presenter: Paul G. Richardson, MD, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Date/Time: Monday, June 3, 8:00-11:00 a.m. Central
Location: Hall A (Poster #369)
Abstract number 8043

For further information, please contact:
Jakob Lindberg, CEO of Oncopeptides
E-mail: [email protected]
Telephone: +46 (0)8 615 20 40

Rein Piir, Head of Investor Relations at Oncopeptides
E-mail: [email protected]
Cell phone: +46 (0)70 853 72 92

This information was submitted for publication at 23.00 CET, May 15, 2019.

About melflufen

Melflufen is a lipophilic peptide-conjugated alkylator that rapidly delivers a highly cytotoxic payload into myeloma cells through peptidase activity. It belongs to the novel class Peptidase Enhanced Cytotoxics (PEnC), which is a family of lipophilic peptides that exhibit increased activity via peptidase cleavage and have the potential to treat many cancers. Peptidases play a key role in protein homeostasis and feature in cellular processes such as cell-cycle progression and programmed cell death. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and is immediately cleaved by peptidases to deliver an entrapped hydrophilic alkylator payload. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the peptidase cleavage, and induces irreversible DNA damage and apoptosis. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies.

About Oncopeptides

Oncopeptides is a pharmaceutical company developing drugs

Data Presentations at ASCO 2019 Highlight Lilly’s Targeted Approach to Developing Treatments for Patients Living with Cancer

On May 15, 2019 Eli Lilly and Company (NYSE: LLY) reported that data from a number of studies across the company’s oncology product portfolio will be presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, May 31-June 4, 2019 (Press release, Eli Lilly, MAY 15, 2019, View Source [SID1234536384]). Data from 23 oral presentations and posters underscore Lilly Oncology’s focus on making a meaningful difference in the lives of people living with cancer, especially those with hard-to-treat tumor types.

"Lilly data at this year’s ASCO (Free ASCO Whitepaper) demonstrate our commitment to offering treatment solutions for patients with the greatest need. We look forward to sharing these findings, with the hope that they will shed light on our progress and future opportunities in difficult-to-treat cancers," said Maura Dickler, M.D., vice president, late phase development, Lilly Oncology. "We are excited to present the first results from RELAY, a Phase 3 study of ramucirumab in metastatic EGFR-mutated non-small cell lung cancer. Lilly will also share early-phase data from several investigational molecules as well as results from collaborative studies. This includes updated findings from the Phase 3 KEYNOTE-189 study of the pemetrexed-pembrolizumab-platinum chemotherapy combination, which has been established as the standard of care for the treatment of first-line metastatic nonsquamous non-small cell lung cancer."

Lung Cancer Data at ASCO (Free ASCO Whitepaper)

Lilly has a decades-old heritage in developing practice-changing medicines for the treatment of lung cancer. Lilly has developed multiple thoracic oncology treatments and continues to study marketed products and investigational molecules in new combinations and settings where they could help specific patient populations.

RELAY is a global, randomized, double-blind Phase 3 trial evaluating ramucirumab in combination with erlotinib, compared to placebo in combination with erlotinib, as a first-line treatment in patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have activating EGFR mutations.

The KEYNOTE-189 trial, a randomized, double-blind, placebo-controlled Phase 3 study, evaluated pemetrexed in combination with pembrolizumab and cisplatin or carboplatin compared with pemetrexed in combination with placebo and cisplatin or carboplatin, in untreated patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression. The KEYNOTE-189 study was conducted by Merck (known as MSD outside the U.S. and Canada) in collaboration with Lilly.

Dr. Dickler added, "In addition to our lung cancer data at ASCO (Free ASCO Whitepaper) this year, we will present results of the Phase 3 ANNOUNCE trial, which studied olaratumab in combination with doxorubicin in soft tissue sarcoma. Unfortunately, this study did not confirm a survival benefit seen in a prior Phase 2 trial. We believe it’s important to share these results to inform the scientific community and to apply these learnings to the future investigation of new therapies in this heterogeneous and difficult-to-treat cancer."

Select studies, along with the dates, times and locations of their data sessions, are highlighted below.

Ramucirumab

Abstract #9000: RELAY: A multinational, double-blind, randomized Phase 3 study of erlotinib (ERL) in combination with ramucirumab (RAM) or placebo (PL) in previously untreated patients with epidermal growth factor receptor mutation-positive (EGFRm) metastatic non-small cell lung cancer (NSCLC) (Kazuhiko Nakagawa)

Oral Abstract Session; Lung Cancer—Non-Small Cell Metastatic
Monday, June 3; 8:00 – 8:12 a.m. CDT; Hall B1
Abstract #2528: Ramucirumab (Ram) and durvalumab (Durva) treatment of metastatic non-small cell lung cancer (NSCLC), gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, and hepatocellular carcinoma (HCC) following progression on systemic treatment(s) (Yung-Jue Bang)

Poster Session: Poster Board #172; Developmental Immunotherapy and Tumor Immunobiology
Saturday, June 1; 8:00 – 11:00 a.m. CDT; Hall A
Abstract #4073: Ramucirumab (RAM) for sorafenib intolerant patients with hepatocellular carcinoma (HCC) and elevated baseline alpha fetoprotein (AFP): Outcomes from two randomized phase 3 studies (REACH, REACH2) (Josep M Llovet)

Poster Session: Poster Board #178; Gastrointestinal (Noncolorectal) Cancer
Monday, June 3; 8:00 – 11:00 a.m. CDT; Hall A
Pemetrexed

Abstract #9013: KEYNOTE-189: Updated OS and progression after the next line of therapy (PFS2) with pembrolizumab (pembro) plus chemo with pemetrexed and platinum vs placebo plus chemo for metastatic nonsquamous NSCLC (Shirish M. Gadgeel)

Poster Session, Poster Board #336, Lung Cancer—Non-Small Cell Metastatic
Sunday, June 2; 8:00 – 11:00 a.m. CDT; Hall A
Poster Discussion Session on Sunday, June 2; 4:30 – 6:00 p.m. CDT; Hall D1
Olaratumab

Abstract #LBA3: ANNOUNCE: A randomized, placebo (PBO)-controlled, double-blind, phase (Ph) III trial of doxorubicin (dox) + olaratumab versus dox + PBO in patients (pts) with advanced soft tissue sarcomas (STS) (William D. Tap)

Plenary Session
Sunday, June 2; 2:45 – 3:00 p.m. CDT; Hall B1
Abemaciclib

Abstract #1017: A phase II study of abemaciclib in patients (pts) with brain metastases (BM) secondary to HR+, HER2- metastatic breast cancer (MBC) (Carey K. Anders)

Poster Session; Poster Board #98; Breast Cancer—Metastatic
Sunday, June 2; 8:00 – 11:00 a.m. CDT; Hall A
Poster Discussion Session on Sunday, June 2; 11:15 a.m. – 12:45 p.m. CDT; Hall D2
Abstract #1042: Next-generation sequencing (NGS) results among hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) patients treated with a CDK4 & 6 inhibitor: A retrospective observational study based on real-world data (Erika Paige Hamilton)

Poster Session: Poster Board #123; Breast Cancer—Metastatic
Sunday, June 2; 8:00 – 11:00 a.m. CDT; Hall A
LOXO-292

Abstract # TPS10066: A phase I study of LOXO-292, a highly selective RET inhibitor, in pediatric patients with RET-altered cancers (Steven G. DuBois)

Poster Session: Poster Board #447b; Pediatric Oncology
Saturday, June 1; 8:00 – 11:00 a.m. CDT; Hall A
Abstract #10045: First experience of LOXO-292 in the management of pediatric patients with RET-altered cancers (Ulrike Gerdemann)

Poster Session: Poster Board #427; Pediatric Oncology
Saturday, June 1; 8:00 – 11:00 a.m. CDT; Hall A
CSF-1R

Abstract #2548: Phase 1 study of LY3022855, a colony-stimulating factor-1 receptor (CSF-1R) inhibitor, in patients with metastatic breast cancer (MBC) or metastatic castration-resistant prostate cancer (MCRPC) (Karen A. Autio)

Poster Session: Poster Board #192; Developmental Immunotherapy and Tumor Immunobiology
Saturday, June 1; 8:00 – 11:00 a.m. CDT; Hall A
ERK Inhibitor

Abstract #3001: A phase I dose escalation (DE) study of ERK inhibitor, LY3214996, in advanced (adv) cancer (CA) patients (pts) (Shubham Pant)

Oral Abstract Session; Developmental Therapeutics and Tumor Biology (Nonimmuno)
Monday, June 3; 8:12 – 8:24 a.m. CDT; S406
PI3 KINASE/mTOR

Abstract #5009: Phase 1b/2 study of enzalutamide (ENZ) with LY3023414 (LY) or placebo (PL) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) after progression on abiraterone (Christopher Sweeney)

Poster Session: Poster Board #121; Genitourinary (Prostate) Cancer
Saturday, June 1; 1:15 – 4:15 p.m. CDT; Hall A
Poster Discussion Session on Saturday, June 1; 4:30 – 6:00 p.m. CDT; Arie Crown Theater
Prexasertib

Abstract #3091: A phase Ib study of prexasertib, a checkpoint kinase (CHK1) inhibitor, and LY3023414, a dual inhibitor of class I phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) in patients with advanced solid tumors (David S. Hong)

Poster Session: Poster Board #83; Developmental Therapeutics and Tumor Biology (Nonimmuno)
Saturday, June 1; 8:00 – 11:00 a.m. CDT; Hall A
Ralimetinib

Abstract #5537: A randomized, double-blind, placebo-controlled phase Ib/II study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine (G) and carboplatin (C) versus GC for women with recurrent platinum-sensitive ovarian cancer (Ignace Vergote)

Poster Session: Poster Board #360; Gynecologic Cancer
Saturday, June 1; 1:15 – 4:15 p.m. CDT; Hall A
TIM-3/PD-L1

Abstract #TPS2654: A phase Ia/b study of TIM-3/PD-L1 bispecific antibody in patients with advanced solid tumors (Matthew David Hellmann)

Poster Session: Poster Board #293a; Developmental Immunotherapy and Tumor Immunobiology
Saturday, June 1; 8:00 – 11:00 a.m. CDT; Hall A
Galunisertib

Abstract #4124: A phase Ib dose-escalation and cohort-expansion study of safety and activity of the transforming growth factor (TGF) β receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer (Davide Melisi)

Poster Session: Poster Board #229; Gastrointestinal (Noncolorectal) Cancer
Monday, June 3; 8:00 – 11:00 a.m. CDT; Hall A
Global Patient Outcomes & Real World Evidence

Abstract #2035: Clinical characteristics, treatment (Tx) patterns, and overall survival (OS) in advanced (Adv) NSCLC patients (Pts) with and without brain metastases (BM) (Emily Nash Smyth)

Poster Session: Poster Board #224; Central Nervous System Tumors
Sunday, June 2; 8:00 – 11:00 a.m. CDT; Hall A
Abstract #2014: Genomic characterization of lung tumors and metastatic (Met) sites in advanced (Adv) NSCLC (Melinda D. Willard)

Poster Session: Poster Board #203; Central Nervous System Tumors
Sunday, June 2; 8:00 – 11:00 a.m. CDT; Hall A
Poster Discussion Session on Sunday, June 2; 4:30 – 6:00 p.m.; S404
Sintilimab

Abstract #7504: Sintilimab for relapsed/refractory (r/r) extranodal NK/T cell lymphoma (ENKTL): A multicenter, single-arm, phase 2 trial (ORIENT-4) (Rong Tao)

Oral Abstract Session; Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Tuesday, June 4; 10:57 – 11:09 a.m. CDT; E451
Abstract #4042: Efficacy and safety of sintilimab in combination with XELOX in first-line gastric or gastroesophageal junction carcinoma (GC/GEJC) (Nong Xu)

Poster Session: Poster Board #147; Gastrointestinal (Noncolorectal) Cancer
Monday, June 3; 8:00 – 11:00 a.m. CDT; Hall A
Abstract #7533: Sintilimab for relapsed/refractory classical Hodgkin’s lymphoma: Extended follow-up on the multicenter, single-arm phase II ORIENT-1 study (Hang Su)

Poster Session: Poster Board #287; Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Monday, June 3; 8:00 – 11:00 a.m. CDT; Hall A
Abstract #8531: Efficacy and safety of neoadjuvant PD-1 blockade with sintilimab in resectable squamous non-small cell lung cancer (sqNSCLC) (Ning Li)

Poster Session: Poster Board #287; Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Sunday, June 2; 8:00 – 11:00 a.m. CDT; Hall A
Abstract #7534: Circulating tumor DNA to predict response and resistance by anti-PD-1 therapy in Chinese relapsed/refractory classic Hodgkin lymphoma (Hang Su)

Poster Session: Poster Board #288; Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Monday, June 3; 8:00 – 11:00 a.m. CDT; Hall A
About Lilly Oncology
For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. To learn more about Lilly’s commitment to people with cancer, please visit www.LillyOncology.com.

About Eli Lilly and Company
Lilly is a global healthcare leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at www.lilly.com and newsroom.lilly.com/social-channels. P-LLY

Agios to Present Clinical Data from its IDH Program at ASCO

On May 15, 2019 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that data from its isocitrate dehydrogenase (IDH) programs will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held May 31-June 4, 2019 in Chicago (Press release, Agios Pharmaceuticals, MAY 15, 2019, View Source [SID1234536383]).

The accepted abstracts are listed below and are available online on the ASCO (Free ASCO Whitepaper) conference website: View Source

Oral Presentation:

Title: A phase 1, open label, perioperative study of AG-120 and AG-881 in recurrent IDH1 mutant, low-grade glioma: Results from cohort 1
Date & Time: Monday, June 3, 2019 from 2:15-2:27 p.m. CT
Oral Abstract Session: Central Nervous System Tumors
Abstract: 2003
Location: S102
Presenter: Ingo K. Mellinghoff, M.D., Memorial Sloan Kettering Cancer Center

Poster Presentations:

Title: Ivosidenib (IVO; AG-120) in IDH1-mutant newly diagnosed acute myeloid leukemia (ND AML): Updated results from a phase 1 study
Poster Session Date & Time: Monday, June 3, 2019 from 8:00-11:00 a.m. CT
Poster Session: Hematologic Malignancies – Leukemia, Myelodysplastic Syndromes, and Allotransplant
Abstract: 7028
Poster Board: 403
Poster Location: Hall A
Author: Gail J. Roboz, M.D., Weill Medical College of Cornell University

Title: Mutant IDH1 inhibitor ivosidenib (IVO; AG-120) in combination with azacitidine (AZA) for newly diagnosed acute myeloid leukemia (ND AML)
Poster Session Date & Time: Monday, June 3, 2019 from 1:15-4:15 p.m. CT
Poster Session: Hematologic Malignancies – Leukemia, Myelodysplastic Syndromes, and Allotransplant
Abstract: 7011
Poster Board: 386
Poster Location: Hall A
Author: Courtney D. DiNardo, M.D., University of Texas MD Anderson Cancer Center

Agios Announces the Randomized Phase 3 ClarIDHy Trial of TIBSOVO® (ivosidenib) Achieved its Primary Endpoint in Previously Treated IDH1 Mutant Cholangiocarcinoma Patients

On May 15, 2019 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that the global Phase 3 ClarIDHy trial of TIBSOVO (ivosidenib) in previously treated cholangiocarcinoma patients with an isocitrate dehydrogenase 1 (IDH1) mutation met its primary endpoint (Press release, Agios Pharmaceuticals, MAY 15, 2019, View Source [SID1234536382]). Treatment with TIBSOVO demonstrated a statistically significant improvement in progression-free survival (PFS) by independent radiology review compared with patients who received placebo. The safety profile observed in the study was consistent with previously published data.

A full analysis of the ClarIDHy trial will be submitted for presentation at the European Society for Medical Oncology Congress taking place in Barcelona, Spain from September 27-October 1, 2019. The company plans to submit a supplemental new drug application for TIBSOVO in previously treated IDH1 mutant cholangiocarcinoma by the end of 2019.

"Advanced cholangiocarcinoma is a life-threatening disease with no currently approved treatment options," said Chris Bowden, M.D., chief medical officer at Agios. "The data from the ClarIDHy Phase 3 trial demonstrate the clinically significant benefit of TIBSOVO in patients with this challenging disease who harbor the IDH1 mutation. We are committed to working with regulators to bring this potential treatment option to patients as quickly as possible. We thank the patients and physicians who participated in the ClarIDHy study, without whom this important advancement would not be possible."

ClarIDHy Phase 3 Trial
The ClarIDHy trial is a global, randomized Phase 3 trial in previously treated IDH1 mutant cholangiocarcinoma patients who have documented disease progression following one or two systemic therapies in the advanced setting. As of the January 31, 2019 data cutoff, 185 patients were randomized.

Patients were randomized 2:1 to receive either single-agent TIBSOVO 500 mg once daily or placebo with crossover to TIBSOVO permitted at the time of documented radiographic progression per RECIST 1.1.
The primary endpoint of the trial is PFS as evaluated by independent radiology review with secondary endpoints including investigator evaluated PFS, safety and tolerability, overall response rate, overall survival, duration of response, PK/PD and quality of life assessments.
The study was designed with 96% power to detect a hazard ratio of 0.5 for PFS (TIBSOVO vs. placebo), with a one-sided alpha of 0.025.
Thermo Fisher Scientific is providing next-generation sequencing to detect IDH1 mutations for all tumor samples as inclusion criteria for enrollment in the study and will develop and commercialize the validated companion diagnostic.
TIBSOVO is not approved in any country for the treatment of patients with advanced cholangiocarcinoma.

About TIBSOVO (ivosidenib)

TIBSOVO is indicated for the treatment of acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in:

Adult patients with newly-diagnosed AML who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.
Adult patients with relapsed or refractory AML.
IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME
Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 25% (7/28) of patients with newly diagnosed AML and 19% (34/179) of patients with relapsed or refractory AML treated with TIBSOVO experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms of differentiation syndrome in patients treated with TIBSOVO included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased. Of the 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. Of the 34 patients with relapsed or refractory AML who experienced differentiation syndrome, 27 (79%) patients recovered after treatment or after dose interruption of TIBSOVO. Differentiation syndrome occurred as early as 1 day and up to 3 months after TIBSOVO initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. If concomitant noninfectious leukocytosis is observed, initiate treatment with hydroxyurea or leukapheresis, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt TIBSOVO until signs and symptoms are no longer severe.

QTc Interval Prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. One patient developed ventricular fibrillation attributed to TIBSOVO. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (e.g., anti-arrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Conduct monitoring of electrocardiograms (ECGs) and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, or electrolyte abnormalities, or in those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary.

Interrupt TIBSOVO if QTc increases to greater than 480 msec and less than 500 msec. Interrupt and reduce TIBSOVO if QTc increases to greater than 500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.

Guillain-Barré Syndrome: Guillain-Barré syndrome occurred in <1% (2/258) of patients treated with TIBSOVO in the clinical study. Monitor patients taking TIBSOVO for onset of new signs or symptoms of motor and/or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, paresthesias, or difficulty breathing. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.

ADVERSE REACTIONS

The most common adverse reactions including laboratory abnormalities (≥20%) were hemoglobin decreased (60%), fatigue (43%), arthralgia (39%), calcium decreased (39%), sodium decreased (39%), leukocytosis (38%), diarrhea (37%), magnesium decreased (36%), edema (34%), nausea (33%), dyspnea (32%), uric acid increased (32%), potassium decreased (32%), alkaline phosphatase increased (30%), mucositis (28%), aspartate aminotransferase increased (27%), phosphatase decreased (25%), electrocardiogram QT prolonged (24%), rash (24%), creatinine increased (24%), cough (23%), decreased appetite (22%), myalgia (21%), constipation (20%), and pyrexia (20%).
In patients with newly diagnosed AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were fatigue (14%), differentiation syndrome (11%), electrocardiogram QT prolonged (11%), diarrhea (7%), nausea (7%), and leukocytosis (7%). Serious adverse reactions (≥5%) were differentiation syndrome (18%), electrocardiogram QT prolonged (7%), and fatigue (7%). There was one case of posterior reversible encephalopathy syndrome (PRES).
In patients with relapsed or refractory AML, the most frequently reported Grade ≥3 adverse reactions (≥5%) were differentiation syndrome (13%), electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis (8%), and tumor lysis syndrome (6%). Serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%). There was one case of progressive multifocal leukoencephalopathy (PML).
DRUG INTERACTIONS

Strong or Moderate CYP3A4 Inhibitors: Reduce TIBSOVO dose with strong CYP3A4 inhibitors. Monitor patients for increased risk of QTc interval prolongation.

Strong CYP3A4 Inducers: Avoid concomitant use with TIBSOVO.

Sensitive CYP3A4 Substrates: Avoid concomitant use with TIBSOVO.

QTc Prolonging Drugs: Avoid concomitant use with TIBSOVO. If co-administration is unavoidable, monitor patients for increased risk of QTc interval prolongation.

LACTATION

Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with TIBSOVO and for at least 1 month after the last dose.

Please see full Prescribing Information, including Boxed WARNING.

About Cholangiocarcinoma
Cholangiocarcinoma (CC) is a rare cancer of the bile ducts within and outside of the liver. Cases that occur within the liver are known as intrahepatic cholangiocarcinoma (IHCC) and those that occur outside the liver are considered extrahepatic. Mutations in IDH1 occur in up to 20% of IHCC cases. Current treatment options for localized disease include surgery, radiation and/or other ablative treatments. There are no approved systemic therapies for cholangiocarcinoma and limited chemotherapy options are available in the advanced setting. Gemcitabine-based chemotherapy is often recommended for newly diagnosed metastatic disease.

TURNING POINT THERAPEUTICS ANNOUNCES FDA CLEARANCE OF INVESTIGATIONAL NEW DRUG APPLICATION FOR TPX-0022, A NOVEL MET/CSF1R/SRC INHIBITOR

On May 15, 2019 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing novel drugs that address treatment resistance, reported clearance by the U.S. Food and Drug Administration (FDA) of its investigational new drug (IND) application for TPX-0022, a novel therapy targeting solid tumors by inhibiting the MET, CSF1R and SRC kinases (Press release, Turning Point Therapeutics, MAY 15, 2019, View Source [SID1234536381]).

Under the IND, the company plans to initiate a Phase 1 first-in-human, open-label clinical study later this year at multiple U.S. sites. The study is designed to assess the safety, tolerability, and preliminary clinical activity of TPX-0022 at escalating doses in patients with advanced or metastatic solid tumors harboring genetic alterations in MET. TPX-0022 has been designed to target MET-driven tumor cells, and also modulate the tumor microenvironment by inhibition of CSF1R.

"The clearance of our IND for TPX-0022 is another important milestone toward our goal to bring a new class of precision therapies to patients," said Athena Countouriotis, M.D., president and chief executive officer. "With our lead drug candidate repotrectinib advancing toward its registrational study, we look forward to beginning our clinical assessment of TPX-0022 in the second half of 2019 following the encouraging preclinical data we recently presented last month at AACR (Free AACR Whitepaper)."

Preclinical data for TPX-0022 were presented for the first time at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Conference in April and highlighted the ability of TPX-0022 to potently inhibit MET-driven cancer cells and the associated signaling of known cancer pathways. This dual mechanism of action showed tumor regression and growth inhibition in multiple xenograft tumor models harboring MET amplification and/or MET exon 14 skipping mutations.