On June 3, 2021 Seagen Inc. (Nasdaq:SGEN) reported that improvements in overall survival (OS) and progression-free survival (PFS) were maintained with long-term follow up from the pivotal HER2CLIMB trial evaluating the addition of TUKYSA (tucatinib) to trastuzumab and capecitabine in patients with HER2-positive metastatic breast cancer (MBC) with and without brain metastases (Press release, Seagen, JUN 3, 2021, View Source [SID1234583437]). Data from the pre-specified exploratory analysis will be presented (Abstract #1043) as part of the virtual scientific program of the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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 overall survival benefit seen with TUKYSA at the time of the primary analysis was maintained after an additional 15.6 months of follow-up (total of 29.6 months), demonstrating a 5.5-month improvement in median OS (24.7 months (95% CI: 21.6, 28.9) for the TUKYSA regimen vs. 19.2 months (95% CI: 16.4, 21.4) for capecitabine and trastuzumab alone). This benefit continued to be generally consistent across pre-specified patient subgroups.

"Late-stage, HER2-positive metastatic cancer has proven difficult to treat," said Giuseppe Curigliano, M.D., Ph.D., Head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, and Associate Professor of Medical Oncology, University of Milano, Italy. "These data further support that treatment with the tucatinib regimen helps patients live longer compared to trastuzumab and capecitabine alone. These benefits were observed across all prespecified subgroups of patients in the trial, including those with or without brain metastases."

"These results support the significant impact that a TUKYSA regimen can have for patients with HER2-positive metastatic breast cancer," said Roger D. Dansey, M.D., Chief Medical Officer of Seagen. "The long-term data from the HER2CLIMB trial showed that the survival benefit was sustained with median overall survival longer than that observed at the primary analysis."

Overall Survival (OS):

Median OS in the TUKYSA arm was 24.7 months (95% CI: 21.6, 28.9) compared to median OS of 19.2 months (95% CI: 16.4, 21.4) in the control arm (HR=0.73 [95% CI: 0.59-0.90]; p=0.004).
Progression Free Survival (PFS):

The median PFS in the TUKYSA arm was 7.6 months (95% CI: 6.9, 8.3), compared to median PFS of 4.9 months (95% CI: 4.1, 5.6) in the control arm (HR=00.57 [95% CI: 0.47-0.70]; p<0.00001).
Safety

The safety profile was generally consistent with the primary analysis. The most common adverse events occurring in more than 20 percent of patients who received TUKYSA included diarrhea, palmar-plantar erythrodysaesthesia syndrome, nausea, fatigue, vomiting, decreased appetite, stomatitis, headache, increased aspartate aminotransferase, anemia, increased alanine aminotransferase, and increased blood bilirubin.
Grade 3 or greater adverse events occurring in more than five percent of patients in either arm were diarrhea (13.1% TUKYSA vs. 8.6% for the control arm), palmar-plantar erythrodysaethesia syndrome (14.1% vs. 9.1%), fatigue (5.4% vs. 4.1%), and increased alanine aminotransferase (5.7% vs. 0.5%).
Discontinuations due to adverse events were infrequent in both arms of the trial, with 5.9 percent in the TUKYSA arm and 4.1 percent in the control arm.
TUKYSA in combination with trastuzumab and capecitabine was approved by the U.S. Food and Drug Administration (FDA) in April 2020 for adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. In February 2021, the European Medicines Agency (EMA) and U.K. Medicines and Healthcare products Regulatory Agency (MHRA) each approved TUKYSA in combination with trastuzumab and capecitabine for the treatment of adult patients with HER2-positive locally advanced or metastatic breast cancer who have received at least two prior anti-HER2 treatment regimens. TUKYSA is also approved in Canada, Switzerland, Singapore and Australia.

In September 2020, Seagen granted Merck, known as MSD outside the U.S. and Canada, exclusive rights to commercialize TUKYSA in Asia, the Middle East and Latin America and other regions outside of the U.S., Canada and Europe.

About HER2CLIMB

HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing tucatinib in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab and T-DM1. The primary endpoint of the trial was PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including overall survival, PFS per BICR in patients with brain metastases at baseline and confirmed objective response rate. Safety data were evaluated throughout the study.1

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. In 2018, more than two million new cases of breast cancer were diagnosed worldwide, including 522,513 in Europe. 2 Between 15 and 20 percent of breast cancer cases are HER2-positive.3 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.3,4,5 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.6,7,8

About TUKYSA (tucatinib)

TUKYSA is an oral medicine that is a tyrosine kinase inhibitor of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell growth (proliferation), and showed anti-tumor activity in HER2-expressing tumor cells. In vivo (in living organisms), TUKYSA inhibited the growth of HER2-expressing tumors. The combination of TUKYSA and the anti-HER2 antibody trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either medicine alone.

U.S. Important Safety Information
Warnings and Precautions

Diarrhea – TUKYSA can cause severe diarrhea including dehydration, hypotension, acute kidney injury, and death. In HER2CLIMB, 81% of patients who received TUKYSA experienced diarrhea, including 12% with Grade 3 diarrhea and 0.5% with Grade 4 diarrhea. Both patients who developed Grade 4 diarrhea subsequently died, with diarrhea as a contributor to death. The median time to onset of the first episode of diarrhea was 12 days and the median time to resolution was 8 days. Diarrhea led to dose reductions of TUKYSA in 6% of patients and discontinuation of TUKYSA in 1% of patients. Prophylactic use of antidiarrheal treatment was not required on HER2CLIMB.

If diarrhea occurs, administer antidiarrheal treatment as clinically indicated. Perform diagnostic tests as clinically indicated to exclude other causes of diarrhea. Based on the severity of the diarrhea, interrupt dose, then dose reduce or permanently discontinue TUKYSA.
Hepatotoxicity – TUKYSA can cause severe hepatotoxicity. In HER2CLIMB, 8% of patients who received TUKYSA had an ALT increase >5 × ULN, 6% had an AST increase >5 × ULN, and 1.5% had a bilirubin increase >3 × ULN (Grade ≥3). Hepatotoxicity led to dose reduction of TUKYSA in 8% of patients and discontinuation of TUKYSA in 1.5% of patients.

Monitor ALT, AST, and bilirubin prior to starting TUKYSA, every 3 weeks during treatment, and as clinically indicated. Based on the severity of hepatotoxicity, interrupt dose, then dose reduce or permanently discontinue TUKYSA.
Embryo-Fetal Toxicity – TUKYSA can cause fetal harm. Advise pregnant women and females of reproductive potential risk to a fetus. Advise females of reproductive potential, and male patients with female partners of reproductive potential, to use effective contraception during TUKYSA treatment and for at least 1 week after the last dose.
Adverse Reactions

Serious adverse reactions occurred in 26% of patients who received TUKYSA. Serious adverse reactions in ≥2% of patients who received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea (2%), abdominal pain (2%), and seizure (2%). Fatal adverse reactions occurred in 2% of patients who received TUKYSA including sudden death, sepsis, dehydration, and cardiogenic shock.

Adverse reactions led to treatment discontinuation in 6% of patients who received TUKYSA; those occurring in ≥1% of patients were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led to dose reduction in 21% of patients who received TUKYSA; those occurring in ≥2% of patients were hepatotoxicity (8%) and diarrhea (6%).

The most common adverse reactions in patients who received TUKYSA (≥20%) were diarrhea, palmar-plantar erythrodysesthesia, nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased appetite, abdominal pain, headache, anemia, and rash.

Lab Abnormalities

In HER2CLIMB, Grade ≥3 laboratory abnormalities reported in ≥5% of patients who received TUKYSA were: decreased phosphate, increased ALT, decreased potassium, and increased AST. The mean increase in serum creatinine was 32% within the first 21 days of treatment with TUKYSA. The serum creatinine increases persisted throughout treatment and were reversible upon treatment completion. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

Drug Interactions

Strong CYP3A or Moderate CYP2C8 Inducers: Concomitant use may decrease TUKYSA activity. Avoid concomitant use of TUKYSA.
Strong or Moderate CYP2C8 Inhibitors: Concomitant use of TUKYSA with a strong CYP2C8 inhibitor may increase the risk of TUKYSA toxicity; avoid concomitant use. Increase monitoring for TUKYSA toxicity with moderate CYP2C8 inhibitors.
CYP3A Substrates: Concomitant use may increase the toxicity associated with a CYP3A substrate. Avoid concomitant use of TUKYSA where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP3A substrate dosage.
P-gp Substrates: Concomitant use may increase the toxicity associated with a P-gp substrate. Consider reducing the dosage of P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicity.
Use in Specific Populations

Lactation: Advise women not to breastfeed while taking TUKYSA and for at least 1 week after the last dose.
Renal Impairment: Use of TUKYSA in combination with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (CLcr < 30 mL/min), because capecitabine is contraindicated in patients with severe renal impairment.
Hepatic Impairment: Reduce the dose of TUKYSA for patients with severe (Child-Pugh C) hepatic impairment.

On June 3, 2021 Leidos (NYSE: LDOS), a FORTUNE 500 science and technology company, reported that it will participate in the Stifel 2021 Virtual Cross Sector Insight Conference webcast (Press release, Leidos, JUN 3, 2021, View Source [SID1234583454]).

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!

Chris Cage, Corporate Controller and incoming Chief Financial Officer, will participate in a question and answer "fireside chat" on Thursday, June 10, 2021 at 4:40 p.m. ET.

A live audio webcast of the event will be available on the Leidos Investor Relations website at View Source A replay of the webcast will be available following the presentation at the same link listed above for 90 days afterward.

On June 3, 2021 Stablix Therapeutics, a biotechnology company pioneering the field of Targeted Protein Stabilization (TPS), reported a $63 million Series A financing led by founding investor Versant Ventures together with NEA, Cormorant, Euclidean Capital and Alexandria Real Estate Equities (Press release, Stablix Therapeutics, JUN 3, 2021, View Source [SID1234583471]).

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!

Many inherited and acquired diseases are caused by insufficient levels of specific proteins. With inherited diseases such as cystic fibrosis, mutations in the CFTR gene produce a protein that remains functional but is subject to excessive ubiquitination, leading to its rapid degradation via the proteasome. Excess ubiquitination is also a feature of cancer, where E3 ubiquitin ligases – enzymes that add ubiquitin to proteins – are frequently upregulated or amplified, driving the degradation of tumor suppressor proteins.

Until now, it has not been possible to inhibit the ubiquitin-proteasome system in a target-selective manner. Stablix’s RESTORED platform generates heterobifunctional small molecules (RESTORACS) that recruit deubiquitinase enzymes to remove ubiquitin from targeted proteins and consequently stabilize or increase target protein levels and activity. The company initially is leveraging the platform to develop programs to treat rare diseases, cancer and immunological disorders.

"Stablix possesses a first-in-category platform that can restore protein stability and function in a target-selective manner," said Carlo Rizzuto, Ph.D., partner at Versant and acting CEO of Stablix. "We are very pleased to launch this company to address this important therapeutic white space for numerous devastating diseases."

Targeted Protein Stabilization (TPS)

Protein stabilization can be thought of as the inverse of protein degradation. The underlying concept of augmenting protein stabilization has been validated in nature. Many viruses encode their own E3 ligases and deubiquitinases to coopt the ubiquitin-proteasome system as part of their life cycles. This demonstrates that the system can be manipulated via exogenous intervention.

The therapeutic value of augmenting protein stabilization has also been demonstrated with proteasome inhibitors. These inhibitors are potent cancer therapeutics but have also been profiled for activity in Mendelian diseases in multiple animal and patient studies. In these studies, proteasome inhibitors were able to increase levels of deficient proteins across a range of targets and organ systems. However, because proteasome inhibitors globally inhibit protein degradation in a non-specific manner, their use outside of oncology is limited by poor tolerability, highlighting the need for targeted approaches.

The Stablix platform originated in the laboratory of Henry Colecraft, Ph.D., John C. Dalton Professor of Physiology and Cellular Biophysics at Columbia University. Co-founders Dr. Colecraft and Scott Kanner, Ph.D., developed an approach to selectively recruit deubiquitinases (DUBs) to proteins of interest. Their pioneering work demonstrated the functional rescue of CFTR and of a second target, KCNQ1, a gene that when mutated causes Long QT syndrome.

"It is gratifying to see the work on precise stabilization of proteins now being translated into new therapies," said Dr. Colecraft. "I look forward to working closely with the Stablix team to bring these treatments to patients."

The company’s RESTORED platform has two primary components. The first is a library of binding moieties capable of recruiting selected DUBs. These recruiting moieties are conjugated with linkers to targeting ligands to create bispecific molecules that co-localize a DUB and a target. Second, a suite of biochemical and functional assays is used to monitor the ubiquitination and functional status of target proteins in cells. Stablix will initially focus pipeline development on rare diseases, oncology and immunology.

Operating plans and scientific leadership

Stablix plans to use the proceeds from the Series A financing to build out its platform and advance a portfolio of protein stabilizers towards the clinic. In addition, the company has established a lab facility in New York City, where it is building a research team led by co-founders Brian Bowman, Ph.D., head of in vitro pharmacology, and Kevin Sprott, Ph.D., head of drug discovery, with Dr. Kanner, head of platform development, leading technology transfer.

For its Scientific Advisory Board, Stablix has recruited a leading group of researchers with extensive experience in DUB biology and chemistry. In addition to Dr. Colecraft, SAB members include Benedikt Kessler, professor of biochemistry and mass spectrometry at the Target Discovery Institute, University of Oxford; Andrew Turnbull, senior principal scientist at Cancer Research UK; Chris Dinsmore, CSO at Kronos Bio; and Chris Roberts, CSO at Black Diamond Therapeutics.

"Stablix’s unique approach presents the company with a massive opportunity to create an impact for patients with rare diseases, cancer or immunological disorders," said Ali Behbahani, M.D., general partner at NEA and a Stablix board member. "We are pleased to join this high-quality syndicate and look forward to the continued development of Stablix’s platform and programs."

On June 3, 2021 Novartis reported the final analysis from the NETTER-1 phase III study comparing treatment using Lutathera (INN: lutetium (177Lu) oxodotreotide / USAN: lutetium Lu 177 dotatate) plus 30 mg octreotide LAR to 60 mg of octreotide LAR in patients with midgut neuroendocrine tumors (Press release, Novartis, JUN 3, 2021, View Source [SID1234583487]). The previously reported primary analysis of the trial demonstrated a statistically significant improvement in progression free survival (PFS) (HR: 0.18*, p < 0.0001)3. In the final analysis of overall survival, a secondary objective of the trial, treatment with Lutathera resulted in a clinically relevant prolongation in median overall survival of 11.7 months [48.0 months (95%CI: 37.4-55.2) compared to the control arm (36.3 months (95%CI: 25.9-51.7)]1. While this analysis did not reach statistical significance (Hazard ratio for OS (HR): 0.84 with 95% CI: (0.60, 1.17) (p=0.30, two-sided))1, the analyses of overall survival may have been impacted by multiple factors, including the crossover of patients from the control arm receiving subsequent radioligand therapy (36% of patients) as well as heterogenous subsequent anti-cancer treatments in both study arms1. No new safety signals emerged in the final analysis1. These results will be presented during the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 4.

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!

Jonathan Strosberg, MD, Principal Investigator and Associate Professor, Section Head, Neuroendocrine Tumor Program at Moffitt Cancer Center, said, "Lutathera plus long-acting octreotide was associated with a nearly 12-month difference in median overall survival compared to high-dose long-acting octreotide in these difficult to treat patients with inoperable midgut NETs progressing under standard dose octreotide LAR treatment. While not statistically significant, I consider this difference to be clinically relevant for these patients. It is also important to emphasize that PFS was the primary endpoint of this study. Moreover, 36% of patients in the control arm crossed over to receive subsequent radioligand treatment, which may have impacted the comparison of survival between both study arms."

"We are proud of our 30-year legacy as an innovator for patients in the neuroendocrine tumor community," said John Tsai, Head of Global Drug Development and Chief Medical Officer for Novartis. "Since its approval by the European Commission in 2017 and the FDA in 2018, Lutathera has been administered to more than 9,000 gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients in Europe and the United States1. We believe in the potential of targeted radioligand therapy and are investing in new discovery and expansion of this important platform, including exploration of new radioisotopes and combinations with complementary mechanisms of action, such as immunotherapy and inhibitors of DNA damage response."

At this final analysis, no new safety signals emerged in the long-term safety follow-up with a median of 6.3 years. In terms of secondary hematological malignancies, no new cases of MDS or acute leukemia were reported in the long term follow up4.

Radioligand therapy combines a targeting compound that binds to receptors expressed by tumors and a radioactive isotope, causing DNA damage that inhibits tumor growth and replication and may lead to cell death5-7. In the case of Lutathera, it binds to somatostatin receptor type 2, which is over-expressed on certain types of cells, such as gastroenteropancreatic neuroendocrine tumor cells8,9.

Novartis has established global expertise and specialized supply chain and manufacturing capabilities across its network of four radioligand therapy production sites, and is further increasing capacity to ensure delivery of future targeted radioligand therapies to patients in need. Novartis is the only pharmaceutical company which is pursuing four different cancer treatment platforms. These include targeted radioligand therapy, cell and gene therapy, targeted therapy and immunotherapy, with an opportunity to combine these platforms for the best outcomes for each cancer patient.

Visit View Source for the latest information from Novartis, including our commitment to the Oncology community, and access to our ASCO (Free ASCO Whitepaper)21 Virtual Scientific Program data presentations (for registered participants).

* HR: 0.21 (0.13, 0.32) in the US Package Insert

About NETTER-1
NETTER-1 is a Phase III international, multicenter, controlled, randomized study that compared treatment using Lutathera every eight weeks plus best standard of care (octreotide LAR 30 mg) to 60 mg of octreotide LAR (dosed every four weeks) in patients with inoperable midgut NETs progressing under standard dose octreotide LAR treatment and overexpressing somatostatin receptors3.

The primary endpoint was to compare the progression-free survival (PFS) after treatment with Lutathera plus octreotide LAR 30 mg versus octreotide LAR 60 mg using RECIST 1.1 criteria3. Secondary trial endpoints included comparing objective response rate, overall survival, time to tumor progression, duration of response and safety between the two study arms3.

About GEP-NETs
Neuroendocrine tumors (NETs) are a type of cancer that originate in neuroendocrine cells throughout the body. NETs are commonly considered slow-growing malignancies. However, some NETs are associated with rapid progression and poor prognosis10-11. In many cases, NET diagnosis is delayed until patients have advanced disease12. Symptoms such as fatigue, diarrhea, and abdominal pain can occur on a daily basis13. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are subdivided into two categories: tumors of the gastrointestinal (GI) tract and pancreas14. There is a need for additional treatment options for inoperable or advanced GEP-NET, including those who have progressed while taking first-line somatostatin analogs.

The estimated age-adjusted incidence, or rate of new cases of NETs in the United States is approximately 6.98/100,000 per year (as of 2012), while the estimated 20-year limited-duration prevalence for 2014, based on the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, was 171,32111. Even though NETs have historically been considered to be rare (orphan disease), their incidence has grown over 500% over the last 3 decades 10,11,12,15.

About Lutathera
Lutathera (lutetium Lu 177 dotatate) is an Advanced Accelerator Applications product approved in the United States for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut and hindgut neuroendocrine tumors in adults16.

Lutathera (lutetium (177Lu) oxodotreotide) is also approved in Europe for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults3.

Important Safety Information
LUTATHERA (lutetium Lu 177 dotatate) is a prescription medicine used to treat adults with a type of cancer known as gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that are positive for the hormone receptor somatostatin, including GEP-NETs in the foregut, midgut, and hindgut.

LUTATHERA is associated with some serious safety considerations, and in some cases these may require a healthcare provider to adjust or stop treatment. Treatment with LUTATHERA will expose patients to radiation which can contribute to long-term radiation exposure. Overall radiation exposure is associated with an increased risk for cancer. The radiation will be detectable in urine for up to 30 days following administration of the drug. It is important to minimize radiation exposure to household contacts consistent with good radiation safety practices as advised by your healthcare provider. Treatment with LUTATHERA increases the risk of myelosuppression, a condition in which bone marrow activity is decreased, resulting in a drop in blood cell counts. You may experience blood-related side effects such as low red blood cells (anemia), low numbers of cells that are responsible for blood clotting (thrombocytopenia), and low numbers of white blood cells (neutropenia). Speak with your healthcare provider if you experience any signs or symptoms of infection, fever, chills, dizziness, shortness of breath or increased bleeding or bruising. Other serious conditions that you may develop as a direct result of treatment with LUTATHERA include blood and bone marrow disorders known as secondary myelodysplastic syndrome and cancer known as acute leukemia. Your healthcare provider will routinely check your blood cell counts and tell you if they are too low or too high. Treatment with LUTATHERA will expose kidneys to radiation and may impair their ability to work as normal. You may be at an increased risk for kidney problems after LUTATHERA treatment if you already have kidney impairment before treatment. In some cases, patients have experienced kidney failure after treatment with LUTATHERA. Your healthcare provider will provide you with an amino acid solution before, during, and after LUTATHERA to help protect your kidneys. You should stay well hydrated before, during, and after your treatment. You should urinate frequently during and after administration of LUTATHERA. Your doctor will monitor your kidney function and may withhold, reduce, or stop your LUTATHERA treatment accordingly. In clinical studies of LUTATHERA, less than 1% of patients were reported to have tumor bleeding (hemorrhage), swelling (edema) or tissue damage (necrosis) to the liver. If you have tumors in your liver, you may be more likely to experience these side effects. Signs that you may be experiencing liver damage include increases in blood markers called ALT, AST and GGT. Your healthcare provider will monitor your liver using blood tests and may need to withhold, reduce, or stop your LUTATHERA treatment accordingly. During your treatment you may experience certain symptoms that are related to hormones released from your cancer. These symptoms may include flushing, diarrhea, difficulty breathing (bronchospasm), and low blood pressure (hypotension), and may occur during or within the 24 hours after your first LUTATHERA treatment. Your healthcare provider will monitor you closely. Speak with your healthcare provider if you experience any of these signs or symptoms. Tell your healthcare provider if you are pregnant. LUTATHERA can harm your unborn baby. Females should use an effective method of birth control during treatment and for 7 months after the final dose of LUTATHERA. Males with female partners should use an effective method of birth control during treatment and for 4 months after the final dose of LUTATHERA. You should not breastfeed during treatment with LUTATHERA and for 2.5 months after your final dose of LUTATHERA. Treatment with LUTATHERA may cause infertility. This is because radiation absorbed by your testes or ovaries over the treatment period falls in the range of exposure where temporary or permanent infertility may occur.

The most common and most serious side effects of LUTATHERA include: vomiting, nausea, decreased blood cell counts, increased liver enzymes, decreased blood potassium levels, and increased blood glucose. Talk to your doctor if you experience any of these, or any other side effects.

Tell your healthcare provider if you are taking any other medications. Somatostatin analogs and corticosteroids may affect how your LUTATHERA treatment works. You should stop taking your long-acting somatostatin analog at least 4 weeks before LUTATHERA treatment. You may continue taking short-acting somatostatin analogs up to 24 hours before your LUTATHERA treatment. Avoid repeated high doses of glucocorticosteroids during treatment with LUTATHERA.

On June 3, 2021 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that members of its management team will participate in the Goldman Sachs 42nd Annual Global Healthcare Conference on Thursday, June 10, 2021 at 2:10 p.m. ET (Press release, Syndax, JUN 3, 2021, View Source [SID1234583438]).

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!

A live webcast of the presentation can be accessed from the Investor section of the Company’s website at www.syndax.com, where a replay of the event will also be available for a limited time.