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.

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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.

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]).

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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.

On May 15, 2019 Sierra Oncology, Inc. (SRRA), a clinical stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported that it will report preliminary clinical data from its Phase 1/2 SRA737 monotherapy study and its Phase 1/2 study of SRA737 in combination with low dose gemcitabine (SRA737+LDG) in two posters being presented on June 1st at the 2019 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, Illinois (Press release, Sierra Oncology, MAY 15, 2019, View Source [SID1234536372]).

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In addition, the company will be hosting an Analyst and Investor Event on Monday, June 3rd, to discuss these clinical findings and potential next steps in the development strategy for SRA737.

The event will feature presentations by two distinguished oncologists:

Professor Johann de Bono, Regius Professor of Cancer Research, Head of the Division of Clinical Studies and Professor in Experimental Cancer Medicine at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, will discuss the critical role of Chk1 in tumor cell survival during replication stress (RS), as well as describe potential opportunities to combine SRA737 with other therapeutic modalities including PARP inhibitors and immunotherapy agents.
Dr. Rebecca Kristeleit, Clinical Senior Lecturer and Honorary Consultant Medical Oncologist at University College London (UCL) Cancer Institute & UCLH Dept. of Oncology, a leading expert in gynecological malignancies, will discuss her clinical experience with SRA737+LDG, and potential development opportunities for this novel combination in the treatment of anogenital cancers.
"We look forward to presenting preliminary data for these first-in-human studies of SRA737 and SRA737+LDG at ASCO (Free ASCO Whitepaper), and to discussing the potential opportunities for further advancement of our differentiated Chk1 inhibitor that these clinical data provide," said Dr. Nick Glover, President and CEO of Sierra Oncology. "The two studies have enrolled patients across a range of tumor indications including a variety of prospectively selected genetic contexts, allowing us to broadly survey the cancer landscape for activity signals in response to administration of SRA737 alone and in combination with non-cytotoxic low dose gemcitabine. These preliminary data have also enabled us to correlate clinical findings with tumor origin and genetic signature, ascertain whether the exogenous induction of replication stress via low dose gemcitabine can enhance SRA737’s activity, and determine potential next steps in the development path for SRA737."

SRA737 Analyst & Investor Event
Date and Time: June 3rd, 6:00 – 7:00 am CT
Location: History event room, Marriot Marquis Hotel, 2121 S Prairie Ave, Chicago, Illinois.

Event registration and webcast information are available through the Sierra Oncology website at www.sierraoncology.com. An archive of the presentation will be accessible after the event through the Sierra Oncology website.

ASCO 2019 Poster Presentations
Title: A first-in-human phase I/II trial of SRA737 (a Chk1 Inhibitor) in subjects with advanced cancer.
Abstract: 3094
Poster #: 86
Poster Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)
Date and Time: Saturday, June 1, 2019, 8:00 – 11:00 am CT
Location: McCormick Place, Event room: Hall A, 2301 S King Dr, Chicago, Illinois

Title: A phase I/II first-in-human trial of oral SRA737 (a Chk1 inhibitor) given in combination with low-dose gemcitabine in subjects with advanced cancer.
Abstract: 3095
Poster #: 87
Poster Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)
Date and Time: Saturday, June 1, 2019, 8:00 – 11:00 am CT
Location: McCormick Place, Event room: Hall A, 2301 S King Dr, Chicago, Illinois

The posters will be available on June 1, 2019 on the company’s website at www.sierraoncology.com

About SRA737 and SRA737+LDG
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). Tumors with high levels of replication stress become reliant on Chk1 to mitigate the potentially catastrophic consequences of excess genomic instability.

Intrinsic sources of replication stress can include genetic alterations in tumor suppressors, oncogenes or DNA Damage Repair genes. Tumors harboring defects in these gene classes are hypothesized to have higher levels of intrinsic replication stress due to dysregulated cell cycle control, increased proliferation demands and increased genomic instability.

SRA737+LDG is a novel drug combination, where non-cytotoxic low dose gemcitabine (LDG) acts as a potent extrinsic inducer of replication stress that potentiates SRA737’s anti-tumor activity. Preclinical models have demonstrated that only subtherapeutic levels of gemcitabine are needed to potentiate SRA737’s anti-tumor effect.

Phase 1/2 clinical trials of SRA737 as monotherapy (NCT02797964) and in combination with low dose gemcitabine (NCT02797977) in multiple solid tumors (ovarian, prostate, non-small cell lung, squamous (head & neck, anal), colorectal, small cell lung, sarcoma, cervical, anogenital) are ongoing. Sierra has also prepared for a potential clinical study of SRA737 in combination with a PARP inhibitor.

Sierra Oncology retains the global commercialization rights to SRA737.

On May 15, 2019 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that it will present new data for several investigational compounds in the Daiichi Sankyo oncology pipeline at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held May 31 to June 4 in Chicago (Press release, Daiichi Sankyo, MAY 15, 2019, https://www.prnewswire.com/news-releases/daiichi-sankyo-data-presentations-at-2019-asco-annual-meeting-highlight-depth-of-adc-pipeline-and-promises-of-oncology-portfolio-300851100.html [SID1234536371]).

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Highlights include new data for two investigational antibody drug conjugates (ADCs) being evaluated in patients with non-small cell lung cancer (NSCLC), including first-in-human results for DS-1062, a TROP2 targeting ADC in advanced NSCLC, and the first phase 1 results for U3-1402, a HER3 targeting ADC, in EGFR mutated, TKI resistant metastatic NSCLC.

"We look forward to showcasing the broad applicability of our proprietary DXd ADC technology with initial results for DS-1062, our third ADC, which we designed to target TROP2 in lung and other cancers, and for U3-1402, which is being studied in lung and breast cancers," said Antoine Yver, MD, MSc, EVP and Global Head, Oncology Research and Development, Daiichi Sankyo. "The ASCO (Free ASCO Whitepaper) meeting presentations demonstrate the depth of our ADC pipeline beyond [fam-] trastuzumab deruxtecan (DS-8201), as well as the breadth of opportunities across our portfolio to translate our innovative science into potential new targeted cancer therapies."

Both DS-1062 and U3-1402 are designed using Daiichi Sankyo’s proprietary DXd ADC technology, which consists of a humanized monoclonal antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. The ADCs were constructed to target and deliver chemotherapy inside cancer cells that express a specific cell surface antigen.

Additional data to be reported at ASCO (Free ASCO Whitepaper) includes a pooled analysis of long-term treatment data from the phase 3 ENLIVEN and phase 1 extension study of pexidartinib in tenosynovial giant cell tumor (TGCT) and first-in-human phase 1 results with DS-1001 in patients with IDH1 mutant gliomas. An overview of data from the Daiichi Sankyo oncology pipeline to be presented includes:

First-in-human phase 1 study of DS-1062a in patients with advanced solid tumors (Abstract 9051. Poster Session: Lung Cancer – Non-Small Cell Metastatic. Sunday, June 2, 8:00 – 11:00 AM CDT)
Safety and preliminary antitumor activity of U3-1402: A HER3-targeted antibody drug conjugate in EGFR TKI-resistant, EGFRm NSCLC (Abstract 9010. Clinical Science Symposium: EGFR and ROS1: Targeting Resistance. Lung Cancer – Non-Small Cell Metastatic. Friday, May 31, 1:00 – 2:30 PM CDT)
A phase III, multicenter, randomized, open label trial of [fam-] trastuzumab deruxtecan (DS-8201a) versus investigator’s choice in HER2-low breast cancer (Abstract TPS1102. Poster Session: Breast Cancer – Metastatic. Sunday, June 2, 8:00 – 11:00 AM CDT)
Phase 1 study of a brain penetrant mutant IDH1 inhibitor DS-1001b in patients with recurrent or progressive IDH1 mutant gliomas (Abstract 2004. Oral Abstract Session: Central Nervous System Tumors. Monday, June 3, 1:15 – 4:15 PM CDT)
Pexidartinib for advanced tenosynovial giant cell tumor (TGCT): Long-term efficacy and safety from the phase 3 ENLIVEN and phase 1 PLX108-01 (TGCT cohort) studies (Abstract 11042. Poster Session: Sarcoma. Saturday, June 1, 8:00 – 11:00 AM CDT)
Responder analysis of Patient-Reported outcomes Measurement Information System (PROMIS) physical function (PF) and worst stiffness among patients with tenosynovial giant cell tumors (TGCT) in the ENLIVEN study (Abstract e18236; Publication Only)
Work productivity loss in patients with Tenosynovial Giant Cell Tumors (TGCT) in the United States (Abstract e22527; Publication Only)
A phase 1 study of milademetan in combination with quizartinib in patients with newly diagnosed or relapsed/refractory FLT3-ITD acute myeloid leukemia (AML) (Abstract TPS7067. Poster Session: Hematologic Malignancies – Leukemia, Myelodysplastic Syndromes, and Allotransplant. Monday, June 3, 8:00 – 11:00 AM CDT)
These are investigational agents that have 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 tenosynovial giant cell tumor (TGCT). For more information, please visit: www.DSCancerEnterprise.com.

On May 15, 2019 Sanofi’s oncology franchise and robust pipeline reported that it will be featured at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, delivering against a renewed strategy to address difficult-to-treat and difficult-to-eradicate cancers, including certain types of multiple myeloma, skin cancer, breast cancer, and lung cancer (Press release, Sanofi, MAY 15, 2019, View Source [SID1234536370]).

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Four key molecules in clinical development are the pillars of Sanofi’s late-stage and emerging oncology pipeline: isatuximab, an investigational anti-CD38 monoclonal antibody; Libtayo (cemiplimab), a PD-1 checkpoint inhibitor in development with Regeneron; SAR439859, an investigational oral selective estrogen receptor degrader (SERD); and SAR408701, an investigational anti-CEACAM5 antibody drug conjugate.

"We have a strategic focus to address unmet patient needs across many therapeutic areas at Sanofi, and currently oncology makes up a sizeable portion of our late-stage pipeline," said John Reed, Head of Research and Development at Sanofi. "Our oncology pipeline is flourishing, offering a progressively expanding diversity of opportunities to help advance the treatment of a variety of cancers. We are excited to showcase this progress at ASCO (Free ASCO Whitepaper)."

Positive results in relapsed/refractory multiple myeloma

Reed continued, "We are particularly excited to share the results from our pivotal Phase 3 ICARIA-MM trial of isatuximab in patients with a difficult-to-treat relapse/refractory multiple myeloma. This is the first of multiple Phase 3 trials with isatuximab, our wholly-owned molecule under investigation for the treatment of multiple myeloma. We look forward to the presentation of data at ASCO (Free ASCO Whitepaper) and believe that the ICARIA-MM data serve as the basis for the first regulatory filings of isatuximab."

A phase 3 randomized, open-label, multicenter study comparing isatuximab, pomalidomide, and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) (Dr. Paul Richardson; Sunday, June 2: Oral Abstract Session, 9:45-12:45 AM, ICARIA presentation,10:57-11:09 AM)
Treatment patterns in patients with multiple myeloma (MM): A retrospective study using Medicare data (Dr. Parameswaran Hari; Publication Only)
Growing body of evidence in advanced cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (CSCC) is one of the most commonly diagnosed skin cancers worldwide. Although the majority of patients with CSCC have a good prognosis when the cancer is found early, the cancer can be especially difficult to treat when it progresses to advanced stages.i-v New longer-term data with Libtayo offer updated efficacy and safety outcomes that add to the growing body of evidence for Libtayo in patients with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation. Libtayo is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

Primary analysis of Phase 2 results of cemiplimab, a human monoclonal anti-PD-1, in patients with locally advanced cutaneous squamous cell carcinoma (Dr. Michael Migden; Saturday, June 1: Poster Display, 1:15-4:15 PM and Poster Discussion, 4:30-6:00 PM)
Phase 2 study of cemiplimab, a human monoclonal anti-PD-1, in patients with metastatic cutaneous squamous cell carcinoma (mCSCC ; Group 1): 12 month follow-up (Dr. Alexander Guminski; Monday, June 3: Poster Display, 1:15-4:15 PM)
Treatment patterns and outcomes among patients with advanced cutnaeous squamous cell carcinoma in a US community oncology setting (Dr. C. Lance Cowey; Publication Only)
Patterns of major surgeries among patients diagnosed with cutaneous squamous cell carcinoma (Chieh-I Chen; Publication Only)
Evolving evidence in breast and lung cancers

Breast cancer is the second most common form of cancer. An estimated 70% of breast cancers are estrogen receptor (ER) positive. SAR439859 is an investigational oral selective estrogen receptor degrader (SERD), a small molecule targeted therapy that binds to estrogen receptors in breast cancer cells to trigger their degradation.

Dose-escalation study of SAR439859, an oral selective estrogen receptor (ER) degrader (SERD), in postmenopausal women with ER+/HER2- metastatic breast cancer (Dr. Aditya Bardia; Poster Display, Sunday, June 2, 8:00-11:00 AM)
Phase 1/2 dose-escalation and expansion study investigating SAR439859 +/- palbociclib in postmenopausal women with estrogen receptor-positive (ER+)/HER2- metastatic breast cancer (Dr. Aditya Bardia; Poster Display, Sunday, June 2, 8:00-11:00 AM)
Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a cell-surface glycoprotein highly expressed in several tumor types, including non-squamous non-small cell lung cancer (NSQ NSCLC). Approximately 20% of lung cancers have a high expression of CEACAM5.

First-in-human Phase 1 study of the antibody-drug conjugate (ADC) SAR408701 in advanced solid tumors: dose-expansion cohort of patients (pts) with non-squamous non-small cell lung cancer (NSQ NSCLC) (Dr. Anas Gazzah; Poster Display, Sunday, June 2, 8:00-11:00 AM)
Additional abstracts supported by Sanofi include:

Abstract title

Abstract number

Oral Abstract, Friday, May 31, 2:45-5:45 PM

Updated results from a randomized phase II study of cabazitaxel
(CAB) versus abiraterone (ABI) or enzalutamide (ENZ) in poor
prognosis metastatic CRPC

5003

Poster Session, Saturday, June 1, 1:15-4:15 PM

Cell-free DNA as a biomarker for taxane treatment in advanced
prostate cancer

5070

Cabazitaxel with Abiraterone Versus Abiraterone Alone
Randomized Trial for Extensive Disease Following Docetaxel: the
CHAARTED2 Trial: A trial of the ECOG-ACRIN Cancer Research
Group (EA8153)

TPS5094

HSD3B1 and Overall Survival in Men with Low-Volume Metastatic
Disease Treated with Androgen Deprivation Therapy or
Chemohormonal Therapy in the CHAARTED Randomized Trial

5020

CALGB 90203 (Alliance): Radical prostatectomy (RP) with or
without neoadjuvant chemohormonal therapy (CHT) in men with
clinically localized, high-risk prostate cancer (CLHRPC).

5079

Oral Abstract, Saturday, June 1, 3:00-6:00 PM

Association of Colon Cancer (CC) Molecular Signatures with
Prognosis and Oxaliplatin Prediction-Benefit in the MOSAIC Trial
(Multicenter International Study of Oxaliplatin/5FU-LV in the
Adjuvant Treatment of Colon Cancer)

3503

Clinical Science Symposium, Sunday, June 2, 8:00-9:00 AM

Evolutionary action score of TP53 analysis in pathologically high-
risk HPV-negative head and neck cancer from a phase II clinical
trial: NRG Oncology RTOG 0234

6010

Poster Session, Monday, June 3, 8:00-11:00 AM

Repeated centralized MDT resectability assessment during first-line
treatment in 1086 Finnish metastatic colorectal cancer (mCRC)
patients nationwide (prospective RAXO study).

3517

Combination of tissues analysis and immune infiltrate in localized
colon cancer using Using artificial intelligence in PETACC8 study

3574

Relative Contribution of Clinical and Molecular Features to
Outcome Within Low and High Risk T and N Groups in Patients
with Stage III Colon Cancers (Alliance)

3520

Is the predictive and prognostic impact of sporadic and familial
microsatellite instable stage III colon cancer different? A pooled
analysis of the PETACC8 and NCCTG N0147 (Alliance) trials

3583

About Isatuximab
Isatuximab is an investigational anti-CD38 monoclonal antibody (mAb) for the treatment of patients with relapsed/refractory multiple myeloma. Developed by Sanofi, isatuximab targets a specific epitope of CD38 capable of triggering multiple, distinct mechanisms of action that are believed to promote programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on multiple myeloma cells and is a cell surface receptor target for antibody-based therapeutics in multiple myeloma and other malignancies. The clinical significance of these findings is under investigation.

Isatuximab is currently being evaluated in multiple ongoing Phase 3 clinical trials in combination with currently available treatments across the multiple myeloma treatment continuum. Isatuximab is also under investigation for the treatment of other hematologic malignancies and solid tumors. Isatuximab is an investigational agent and its safety and efficacy have not been evaluated by the U.S. Food and Drug Administration, the European Medicines Agency, or any other regulatory authority.

About Libtayo
Libtayo is approved in the U.S., Canada and Brazil, and is under review by the European Commission following a positive opinion by the Committee for Medicinal Products for Human Use (CHMP). In the U.S., Libtayo is approved for the treatment of patients with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation.vi The generic name for Libtayo in the U.S. is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.

Libtayo is also being investigated in potential registrational trials in non-small cell lung cancer, basal cell carcinoma and cervical cancer, along with additional trials in squamous cell carcinoma of the head and neck, melanoma, colorectal cancer, prostate cancer, multiple myeloma, Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. These trials are designed to investigate Libtayo as monotherapy; in combination with conventional treatments like chemotherapy; or in combination with other investigational agents, including vaccines, oncolytic viruses and bispecific antibodies, among others. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

What is the most important information I should know about Libtayo?
Libtayo is a medicine that may treat a type of skin cancer by working with your immune system. Libtayo can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any symptoms of the following problems or these symptoms get worse:

Lung problems (pneumonitis). Signs and symptoms of pneumonitis may include new or worsening cough, shortness of breath, and chest pain.
Intestinal problems (colitis) that can lead to tears or holes in your intestine. Signs and symptoms of colitis may include diarrhea (loose stools) or more frequent bowel movements than usual; stools that are black, tarry, sticky or that have blood or mucus; and severe stomach-area (abdomen) pain or tenderness.
Liver problems (hepatitis). Signs and symptoms of hepatitis may include yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual.
Hormone gland problems (especially the adrenal glands, pituitary, thyroid and pancreas). Signs and symptoms that your hormone glands are not working properly may include headaches that will not go away or unusual headaches, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, feeling cold, constipation, deeper voice, very low blood pressure, urinating more often than usual, nausea or vomiting, stomach-area (abdomen) pain, and changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness.
Kidney problems, including nephritis and kidney failure. Signs of these problems may include decrease in your amount of urine, blood in your urine, swelling in your ankles, and loss of appetite.
Skin problems. Signs of these problems may include rash, itching, skin blistering, and painful sores or ulcers in the mouth, nose, throat, or genital area.
Problems in other organs. Signs of these problems may include headache, tiredness or weakness, sleepiness, changes in heartbeat (such as beating fast, seeming to skip a beat, or a pounding sensation), confusion, fever, muscle weakness, balance problems, nausea, vomiting, stiff neck, memory problems, seizures (encephalitis), swollen lymph nodes, rash or tender lumps on skin, cough, shortness of breath, vision changes, or eye pain (sarcoidosis), seeing or hearing things that are not there (hallucinations), severe muscle weakness, low red blood cells (anemia), bruises on the skin or bleeding, and changes in eyesight.
Rejection of a transplanted organ. Your doctor should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had.
Infusion (IV) reactions that can sometimes be severe and life-threatening. Signs of these problems may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, fever, feeling of passing out, back or neck pain, and facial swelling.
Getting medical treatment right away may help keep these problems from becoming more serious.

Your healthcare provider will check you for these problems during your treatment with Libtayo. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may delay or completely stop treatment if you have severe side effects.

Before you receive Libtayo, tell your healthcare provider about all your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus;
have had an organ transplant;
have lung or breathing problems;
have liver or kidney problems;
have diabetes;
are pregnant or plan to become pregnant; Libtayo can harm your unborn baby.
Females who are able to become pregnant:
Your healthcare provider will give you a pregnancy test before you start treatment.
You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of Libtayo. Talk with your healthcare provider about birth control methods that you can use during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Libtayo.
are breastfeeding or plan to breastfeed. It is not known if Libtayo passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of Libtayo.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Libtayo include tiredness, rash, and diarrhea. These are not all the possible side effects of Libtayo. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals and Sanofi at 1-877-542-8296.

Please see accompanying full Prescribing Information, including Medication Guide.

What is Libtayo?

Libtayo is a prescription medicine used to treat people with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.

It is not known if Libtayo is safe and effective in children.