On November 18, 2019 KIYATEC, Inc. and CarThera reported that they have entered into a clinical collaboration for the purpose of advancing innovation and improving treatments for patients diagnosed with glioblastoma, a highly aggressive form of brain cancer that afflicts more than 130,000 patients worldwide per year and is characterized by historically poor clinical outcomes (Press release, KIYATEC, NOV 18, 2019, View Source [SID1234551434]). The collaboration will focus on accelerating the development and validation of their emerging technologies to improve both the selection and effectiveness of drugs commonly recommended and used to treat the disease.

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!

"Relevant clinical advances that improve outcomes for patients with glioblastoma have been few and far between over the last two decades," said Frederic Sottilini, CEO of CarThera. "Despite multimodal therapy, median survival remains around 15 months for these patients, virtually all of whom recur. Our goal is to optimize the selection and delivery of drug therapies to extend the lives of patients with glioblastoma."

The two companies were brought together by one of the world’s leading neuro-oncology and glioblastoma experts, John de Groot, M.D., professor and chairman ad interim, The University of Texas MD Anderson Cancer Center, who recognized the synergistic nature of their respective clinical initiatives. CarThera is currently conducting a multi-center clinical study of its novel ultrasound technology, SonoCloud-9, designed to increase the permeability of the blood brain barrier to improve the delivery of chemotherapeutic agents to the brains of patients with recurrent glioblastoma. KIYATEC is conducting a multi-center clinical study of its ex vivo 3D cell culture technology to accurately predict pre-treatment, patient-specific response to recommended standard of care cancer drugs for newly diagnosed and recurrent glioblastoma.

"As someone who cares for patients with glioblastoma, I applaud the efforts of CarThera and KIYATEC to bring evidence-based advances to the clinic for the purpose of improving outcomes for patients with glioblastoma," said Dr. de Groot. "I envision these two technologies as being complementary with the potential to transform the way in which neuro-oncologists manage glioblastoma patients."

Under the terms of the clinical collaboration, KIYATEC will conduct ex vivo drug response profiling on glioblastoma tissue samples from patients enrolled in CarThera’s clinical study. CarThera will benefit from having ex vivo drug response profiling for patients enrolled in its study, while KIYATEC will correlate its patient-specific, pre-treatment drug response predictions with actual clinical outcomes of patients in CarThera’s study. For both companies, this collaboration represents an opportunity to enrich their portfolios of clinical evidence with the goal of helping clinicians improve outcomes for their patients with glioblastoma.

"Both of our companies are dedicated to ensuring that glioblastoma patients receive the most appropriate drug therapy at the right time, and that the efficacy of that therapy is maximized to its fullest therapeutic potential," said Matthew Gevaert, CEO and co-founder of KIYATEC. "We believe that this clinical collaboration has the potential to help us accelerate and deliver on the long-awaited promise of personalized medicine for these deserving patients."

Both companies will be sending delegates to the 24th Annual Meeting of the Society for Neuro-Oncology, November 20-24 in Phoenix, Arizona.

On November 18, 2019 AVEO Oncology (NASDAQ: AVEO) reported the presentation of updated data from the Phase 3 TIVO-3 trial (Press release, AVEO, NOV 18, 2019, View Source [SID1234551433]). The data were presented on Saturday, November 16, 2019, at the 18th International Kidney Cancer Symposium in Miami, in an oral presentation titled "TIVO-3: A Phase 3 Study to Compare Tivozanib to Sorafenib in Subjects with Refractory Advanced Renal Cell Carcinoma (RCC) Overall Survival 2-Year Update" by Sumanta (Monty) Kumar Pal, M.D., Associate Clinical Professor, Department of Medical Oncology and Therapeutics Research, and Co-director, Kidney Cancer Program, at City of Hope Comprehensive Cancer Center. TIVO-3 is the Company’s Phase 3 randomized, controlled, multi-center, open-label study to compare tivozanib (FOTIVDA), the Company’s vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI), to sorafenib in 350 subjects with highly refractory metastatic RCC.

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!

As previously presented, results for the intent to treat (ITT) population showed that tivozanib significantly improved progression free survival (PFS), the study’s primary endpoint, and overall response rate (ORR) compared to sorafenib, with responses to tivozanib more durable than sorafenib. Newly presented data include the recently announced interim overall survival (OS) hazard ratio (HR) of 0.99 within the ITT population, as well as results from two prespecified subgroup analyses of patients previously treated with a checkpoint inhibitor and a VEGF-TKI, or two VEGFR-TKIs. Superior PFS and ORR, as well as OS HRs below 1, favoring tivozanib, were observed in the prespecified subgroups. Tivozanib was shown to have lower overall rates of adverse events and fewer dose interruptions and reductions versus sorafenib, indicating better patient tolerability. A copy of the presentation is available in the Publications & Presentations section of AVEO’s website.

"Until the TIVO-3 trial results, limited prospective data existed to inform sequencing of treatment after checkpoint inhibitor therapy, the emergent standard of care in earlier-line treatment," said Dr. Pal. "Tivozanib’s outcomes within this population, as well as in those receiving two prior VEGF-TKIs, suggest an important potential role for tivozanib in the evolving refractory advanced RCC setting. Furthermore, tivozanib’s unique tolerability profile is potentially well suited to an advanced setting, where many are reluctant to accept higher rates of adverse events following multiple courses of therapy."

"Tivozanib is the first RCC treatment to show superior outcomes over another active therapy in a Phase 3 study in the third/fourth line setting, a high unmet need population that is growing due to longer survival in earlier lines of therapy," said Michael Bailey, president and chief executive officer of AVEO. "We look forward to completing a final OS analysis of TIVO-3 in June 2020 after our planned submission of a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2020. The continued separation of the PFS curves and the positive trend in OS HR observed from the first to the second interim analyses of TIVO-3, together with tenfold more patients remaining progression free and on tivozanib vs. sorafenib therapy, make us believe that the final OS HR could continue to improve."

AVEO recently provided a regulatory update following a meeting with the FDA to discuss results from the August 2019 OS analysis of the TIVO-3 trial. The Company intends to submit an update to the TIVO-3 statistical analysis plan to the FDA allowing for the final OS analysis to be conducted, followed by an NDA submission in the first quarter of 2020, and expects to report results from a final OS analysis of the TIVO-3 trial in June 2020. The FDA and the Company agreed that if, during the review, the final analysis yields an OS HR above 1.00, the Company will withdraw its NDA application. The FDA informed the Company that an Oncologic Drugs Advisory Committee panel would likely be convened to review the final tivozanib data package.

Results in Detail

Patients enrolled in the TIVO-3 trial (n=350) were randomized and stratified for prior regimen and IMDC prognostic score. Prior treatment regimens included prior checkpoint inhibitor and VEGF TKI therapies (n=91), two prior VEGF TKI therapies (n=159) and prior VEGF TKI and other therapies (n=100). Statistically significant improvements favoring tivozanib were reported for the primary endpoint of PFS (HR=0.73; p=0.0165) and secondary endpoint of ORR (18% vs. 8%; p=0.02). Improvements were also observed in patients receiving prior checkpoint inhibitor and VEGF TKI therapies and two prior VEGF TKI therapies:

Prior Checkpoint Inhibitor + VEGFR TKI

For the secondary endpoint of OS, two prespecified analyses have been conducted, the first at a data cutoff date of October 4, 2018, and the second at August 15, 2019. The OS HR, which assesses the relative risk of death for the entirety of the data set, was 0.99 (95% CI: 0.76-1.29; p=0.95) for the ITT population at the second analysis, and improvement from an HR of 1.12 observed at the first analysis. At the second analysis, OS HR for patients receiving prior checkpoint inhibitor and VEGF TKI therapies was 0.88, and 0.98 for patients treated with two prior VEGF TKI therapies. Both hazard ratios were improved from hazard ratios of 1.14 and 1.05, respectively, observed at the first analysis.

As of the August 15, 2019 data cutoff date, median OS, a point in time value of the OS when half of the patients within each arm are still alive, was 16.4 months for tivozanib (95% CI: 13.4-22.2) and 19.7 months for sorafenib (95% CI: 15.0-24.2). As of the second data cutoff date, twenty patients remained progression free on the tivozanib arm and two on the sorafenib arm, with a median duration on study of 32.5 months.

Grade 3 or higher adverse events were consistent with those observed in previous tivozanib trials. Infrequent but severe adverse events reported in greater number in the tivozanib arm were thrombotic events similar to those observed in previous tivozanib studies. The most common adverse event in patients receiving tivozanib was hypertension, an adverse event known to reflect effective VEGF pathway inhibition.

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) discovered by Kyowa Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma (RCC) in the European Union plus Norway, New Zealand and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications.1,2 Tivozanib is being studied in the TIVO-3 trial, which is intended to support a regulatory submission of tivozanib in the U.S. as a treatment for relapsed/refractory RCC. Tivozanib has been shown to significantly reduce regulatory T-cell production in preclinical models3 and has demonstrated synergy in combination with nivolumab (anti PD-1) in a Phase 2 study in RCC4. Tivozanib has been investigated in several tumor types, including renal cell, hepatocellular, colorectal, ovarian and breast cancers.

On November 18, 2019 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that results from a number of studies across its growing breast cancer portfolio will be presented at the San Antonio Breast Cancer Symposium (SABCS) on December 10-14, 2019 (Press release, Genentech, NOV 18, 2019, View Source [SID1234551432]). These data include new results in HER2-positive breast cancer and studies of new molecules in hormone receptor-positive (HR-positive) breast cancer.

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!

"For the past three decades, we have remained dedicated to improving outcomes for people with breast cancer," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "This sustained commitment is exemplified by new data for our approved and investigational medicines across the spectrum of breast cancer being presented at SABCS this year."

Key presentations

New data will be presented from a second interim overall survival (OS) analysis of the Phase III APHINITY trial evaluating Perjeta (pertuzumab) and Herceptin (trastuzumab) plus chemotherapy (the Perjeta-based regimen), compared to Herceptin and chemotherapy, as an adjuvant treatment for HER2-positive early breast cancer (eBC). This latest interim OS analysis also includes updated descriptive invasive disease-free survival and cardiac safety data.

Genentech will also present data from the primary analysis of the Phase III FeDeriCa study which evaluated a new investigational fixed-dose combination (FDC) of Perjeta and Herceptin administered as a single subcutaneous formulation in combination with intravenous chemotherapy. The FDC is administered under the skin in just minutes, significantly reducing the time spent receiving treatment and providing people with HER2-positive breast cancer a potential new treatment option for faster delivery of the Perjeta-based regimen.

Data will also be presented from studies in HR-positive breast cancer, including findings from early studies investigating Genentech’s pipeline molecules GDC-9545, a selective estrogen receptor degrader, and GDC-0077, a mutant selective PI3Kα inhibitor.

Overview of Genentech studies to be presented at SABCS 2019

Medicine(s)

Abstract title

Abstract number

(date, time, location of presentation)

HER2-positive breast cancer

Perjeta and Herceptin

Interim OS analysis of APHINITY (BIG 4-11): a randomized multicenter, double-blind, placebo-controlled trial comparing chemotherapy plus trastuzumab plus pertuzumab versus chemotherapy plus trastuzumab plus placebo as adjuvant therapy in patients with operable HER2-positive eBC

Abstract GS1-04

(Oral)

Wednesday, December 11
9:30 – 9:45 AM CST

Hall 3

Perjeta and Herceptin

Subcutaneous trastuzumab and hyaluronidase-oysk with intravenous pertuzumab and docetaxel in HER2-positive advanced breast cancer: final analysis of the Phase IIIb, multicenter, open-label, single-arm MetaPHER study

Abstract P1-18-05

(Poster)

Wednesday, December 11
5:00 – 7:00 PM CST

Hall 1

Perjeta and Herceptin

Risk of recurrence and death in patients with early HER2-positive breast cancer who achieve a pathological complete response (pCR) after different types of HER2-targeted therapy: a retrospective exploratory analysis

Abstract P1-18-01

(Poster)

Wednesday, December 11
5:00 – 7:00 PM CST

Hall 1

Perjeta and Herceptin

Use of pertuzumab in combination with taxanes for HER2-positive metastatic breast cancer (MBC): analysis of United States electronic health records

Abstract P1-18-14

(Poster)

Wednesday, December 11
5:00 – 7:00 PM CST

Hall 1

Kadcyla (ado-trastuzumab emtansine)

Cardiac events in patients with HER2-positive MBC who have low left ventricular ejection fraction prior to initiating treatment with ado-trastuzumab emtansine: a retrospective cohort study using electronic health record data

Abstract P1-18-11

(Poster)

Wednesday, December 11
5:00 – 7:00 PM CST

Hall 1

Tecentriq (atezolizumab), Kadcyla, Perjeta and Herceptin

Atezolizumab in combination with ado-trastuzumab emtansine or with trastuzumab and pertuzumab in patients with HER2-positive breast cancer and atezolizumab with doxorubicin and cyclophosphamide in HER2-negative breast cancer: safety and biomarker outcomes from a multi-cohort Phase Ib study

Abstract PD1-05

(Poster discussion)

Wednesday, December 11
5:00 – 7:00 PM CST

Hemisfair Ballroom

Perjeta and Herceptin

Subcutaneous administration of the fixed-dose combination of trastuzumab and pertuzumab in combination with chemotherapy in HER2-positive eBC: primary analysis of the Phase III, multicenter, randomized, open-label, two-arm FeDeriCa study

Abstract PD4-07

(Poster discussion)

Thursday, December 12

7:00 – 9:00 AM CST

Stars at Night Ballroom 1&2

Kadcyla and Perjeta

Association of immune gene expression with outcome in the MARIANNE Phase III clinical trial in HER2-positive MBC

Abstract PD5-11

(Poster discussion)

Thursday, December 12

7:00 – 9:00 AM CST

Stars at Night Ballroom 3&4

Kadcyla and Herceptin

Adjuvant ado-trastuzumab emtansine versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: KATHERINE subgroup analysis

Abstract P3-14-01

(Poster)

Thursday, December 12

5:00 – 7:00 PM CST

Hall 1

Herceptin

Palbociclib in combination with trastuzumab and endocrine therapy versus treatment of physician’s choice in metastatic HER2-positive and HR-positive breast cancer with PAM50 luminal intrinsic subtype (SOLTI-1303 PATRICIA II): a multi-center, randomized, open-label, Phase II trial

Abstract OT2-02-06

(Poster)

Thursday, December 12

5:00 – 7:00 PM CST

Hall 1

Kadcyla and Herceptin

Cost-effectiveness of ado-trastuzumab emtansine versus trastuzumab for the adjuvant treatment of patients with residual invasive HER2-positive eBC in the United States

Abstract P6-13-01

(Poster)

Saturday, December 14

7:00 – 9:00 AM CST

Hall 1

Hormone receptor-positive

GDC-0077

A first-in-human Phase Ia dose escalation study of GDC-0077, a p110a-selective and mutant-degrading PI3K inhibitor, in patients with PIK3CA-mutant solid tumors

Abstract OT1-08-04

(Poster)

Wednesday, December 11

5:00 – 7:00 PM CST

Hall 1

GDC-0077

A Phase Ib dose escalation study evaluating the mutant selective PI3K-alpha inhibitor GDC-0077 in combination with letrozole with and without palbociclib in patients with PIK3CA-mutant HR-positive, HER2-negative breast cancer

Abstract P1-19-46

(Poster)

Wednesday, December 11

5:00 – 7:00 PM CST

Hall 1

GDC-9545

A first-in-human Phase I study to evaluate the oral selective estrogen receptor degrader (SERD), GDC-9545, in postmenopausal women with HR-positive/HER2-negative MBC

Abstract PD7-05

(Poster discussion)

Thursday, December 12

5:00 – 7:00 PM CST

Stars at Night Ballroom 1&2

Triple-negative breast cancer

Tecentriq

Exploratory analytical harmonization of PD-L1 immunohistochemistry assays in advanced triple negative breast cancer (TNBC): a retrospective substudy of IMpassion130

Abstract PD1-07

(Poster discussion)

Wednesday, December 11

5:00 – 7:00 PM CST

Hemisfair Ballroom

Tecentriq

Systemic corticosteroid use in patients with metastatic TNBC treated with first-line therapy in the United States

Abstract P2-15-09

(Poster)

Thursday, December 12

7:00 – 9:00 AM CST

Hall 1

ipatasertib

Expression of PD-L1 is independent of PIK3CA/AKT1/PTEN alterations in TNBC and is not associated with response to ipatasertib plus paclitaxel

Abstract P4-10-23

(Poster)

Friday, December 13

7:00 – 9:00 AM CST

Hall 1

About Perjeta (pertuzumab)

Perjeta is a medicine that targets the HER2 receptor, a protein found on the outside of many normal cells and in high quantities on the outside of cancer cells in HER2-positive cancers. Perjeta is designed specifically to prevent the HER2 receptor from pairing (or ‘dimerizing’) with other HER receptors (EGFR/HER1, HER3 and HER4) on the surface of cells, a process that is believed to play a role in tumor growth and survival. Binding of Perjeta to HER2 may also signal the body’s immune system to destroy the cancer cells. The mechanisms of action of Perjeta and Herceptin are believed to complement each other, as both bind to the HER2 receptor, but to different places. The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of HER signaling pathways, thus preventing tumor cell growth and survival.

Perjeta Indication Statement

Perjeta (pertuzumab) is approved for use in combination with Herceptin (trastuzumab) and docetaxel in people who have HER2-positive breast cancer that has spread to different parts of the body (metastatic) and who have not received anti-HER2 therapy or chemotherapy for metastatic breast cancer.

Perjeta (pertuzumab) is approved for use in combination with Herceptin (trastuzumab) and chemotherapy for:

use prior to surgery (neoadjuvant treatment) in people with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (tumor is greater than two centimeters in diameter or node-positive). Perjeta should be used as part of a complete treatment regimen for early breast cancer.
use after surgery (adjuvant treatment) in people with HER2-positive early breast cancer that has a high likelihood of coming back.
Important Safety Information

Side effects with Perjeta

Not all people have serious side effects; however, side effects with Perjeta therapy are common. It is important for patients to know what side effects may happen and what symptoms patients should watch for.
A patient’s doctor may stop treatment if serious side effects happen. Patients should be sure to contact their healthcare team right away if they have questions or are worried about any side effects.
Most serious side effects of Perjeta

Perjeta may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure).

A patient’s doctor may run tests to monitor the patient’s heart function before and during treatment with Perjeta.
Based on test results, a patient’s doctor may hold or discontinue treatment with Perjeta.
Patients should contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than five pounds in 24 hours, dizziness or loss of consciousness.
Receiving Perjeta during pregnancy can result in the death of an unborn baby and birth defects.

Birth control should be used while receiving Perjeta and for seven months after a patient’s last dose of Perjeta. If a patient is a mother who is breastfeeding, she should talk with her doctor about either stopping breastfeeding or stopping Perjeta.
If a patient thinks she may be pregnant, she should contact her healthcare provider immediately.
If a patient is exposed to Perjeta during pregnancy, or becomes pregnant while receiving Perjeta or within seven months following her last dose of Perjeta in combination with Herceptin, she is encouraged to report Perjeta exposure to Genentech at (888) 835-2555.
Other possible serious side effects

Perjeta should not be used in patients who are allergic to pertuzumab or to any of the ingredients in Perjeta.
Infusion-related reactions: Perjeta is a medicine that is delivered into a vein through a needle. Perjeta has been associated with infusion-related reactions, some fatal. The most common infusion-related reactions when receiving Perjeta, Herceptin and docetaxel were feeling tired, abnormal or altered taste, allergic reactions, muscle pain and vomiting. The most common infusion-related reactions when receiving Perjeta alone were fever, chills, feeling tired, headache, weakness, allergic reactions and vomiting.
Severe allergic reactions: Some people receiving Perjeta may have severe allergic reactions, called hypersensitivity reactions or anaphylaxis, which may happen quickly and may affect many areas of the body. Severe allergic reactions, some fatal, have been observed in patients treated with Perjeta.
Most common side effects

The most common side effects of Perjeta when given with Herceptin and docetaxel for treatment of breast cancer that has spread to other parts of the body (metastatic) are:

Diarrhea
Hair loss
Low levels of white blood cells with or without fever
Nausea
Feeling tired
Rash
Damage to the nerves (numbness, tingling, pain in hands/feet)
The most common side effects of Perjeta when given with Herceptin and chemotherapy as part of an early breast cancer regimen before surgery are:

Constipation
Damage to the nerves (numbness, tingling, pain in hands/feet)
Diarrhea
Feeling tired
Hair loss
Headache
Low levels of red blood cells
Low levels of white blood cells with or without fever
Low platelet count
Mouth blisters or sores
Nausea
Pain in the muscles
Vomiting
Weakness
Side effects may vary based on chemotherapy regimen.

The most common side effects of Perjeta when given with Herceptin and chemotherapy as part of an early breast cancer regimen after surgery are:

Diarrhea
Nausea
Hair loss
Feeling tired
Damage to the nerves (numbness, tingling, pain in hands/feet)
Vomiting
Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please see the Perjeta full Prescribing Information for additional Important Safety Information, including most serious side effects, at View Source

About Herceptin (trastuzumab)

Herceptin is a personalized medicine designed to specifically block the HER2 protein on the surface of some cancer cells. Based on preclinical studies, this biologic antibody is believed to work by attaching to HER2 receptors to stop signals that make the tumor cells grow and divide, and also by signaling the body’s immune system to destroy the cancer cells.

Herceptin Indication Statements

Adjuvant Breast Cancer

Herceptin is approved for the treatment of early stage breast cancer that is Human Epidermal growth factor Receptor 2-positive (HER2-positive) and has spread into the lymph nodes, or is HER2-positive and has not spread into the lymph nodes. If it has not spread into the lymph nodes, the cancer needs to be estrogen receptor/progesterone receptor (ER/PR)-negative or have one high-risk feature.* Herceptin can be used in several different ways:

As part of a treatment course including the chemotherapy drugs doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel. This treatment course is known as "AC→TH."
With the chemotherapy drugs docetaxel and carboplatin. This treatment course is known as "TCH."
Alone after treatment with multiple other therapies, including an anthracycline (doxorubicin)-based therapy (a type of chemotherapy).
Patients are selected for therapy based on an FDA-approved test for Herceptin.

*High risk is defined as ER/PR-positive with one of the following features: tumor size greater than 2 cm, age less than 35 years, or tumor grade 2 or 3.

Metastatic Breast Cancer

Herceptin has two approved uses in metastatic breast cancer:

Herceptin in combination with the chemotherapy drug paclitaxel is approved for the first-line treatment of Human Epidermal growth factor Receptor 2-positive (HER2-positive) metastatic breast cancer.
Herceptin alone is approved for the treatment of HER2-positive breast cancer in patients who have received one or more chemotherapy courses for metastatic disease.
Patients are selected for therapy based on an FDA-approved test for Herceptin.

Important Safety Information

Possible serious side effects with Herceptin

Not all people have serious side effects, but side effects with Herceptin therapy are common.

Although some people may have a life-threatening side effect, most do not.

A patient’s doctor will stop treatment if any serious side effects occur.

Herceptin is not for everyone. A patient should be sure to contact their doctor if they are experiencing any of the following:

HEART PROBLEMS

These include heart problems—such as congestive heart failure or reduced heart function—with or without symptoms. The risk for and seriousness of these heart problems were highest in people who received both Herceptin and a certain type of chemotherapy (anthracycline). In a study of adjuvant (early) breast cancer, one patient died of significantly weakened heart muscle. A patient’s doctor will check for signs of heart problems before, during, and after treatment with Herceptin.

INFUSION REACTIONS, including:

Fever and chills
Feeling sick to your stomach (nausea)
Throwing up (vomiting)
Pain (in some cases at tumor sites)
Headache
Dizziness
Shortness of breath
These signs usually happen within 24 hours after receiving Herceptin.

A patient should be sure to contact their doctor if they:

Are a woman who could become pregnant, or may be pregnant

Herceptin may result in the death of an unborn baby or birth defects. Contraception should be used while receiving Herceptin and for seven months after a patient’s last dose of Herceptin. If a patient is or becomes pregnant while receiving Herceptin or within seven months after their last dose of Herceptin, the patient should immediately report Herceptin exposure to Genentech at (888) 835-2555.

Have any signs of SEVERE LUNG PROBLEMS, including:

Severe shortness of breath
Fluid in or around the lungs
Weakening of the valve between the heart and the lungs
Not enough oxygen in the body
Swelling of the lungs
Scarring of the lungs
A patient’s doctor may check for signs of severe lung problems when he or she examines the patient.

Have LOW WHITE BLOOD CELL COUNTS

Low white blood cell counts can be life threatening. Low white blood cell counts were seen more often in patients receiving Herceptin plus chemotherapy than in patients receiving chemotherapy alone.

A patient’s doctor may check for signs of low white blood cell counts when he or she examines the patient.

Side effects seen most often with Herceptin

Some patients receiving Herceptin for breast cancer had the following side effects:

Fever
Feeling sick to your stomach (nausea)
Throwing up (vomiting)
Infusion reactions
Diarrhea
Infections
Increased cough
Headache
Feeling tired
Shortness of breath
Rash
Low white and red blood cell counts
Muscle pain
A patient should contact their doctor immediately if they have any of the side effects listed above.

Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please see the Herceptin full Prescribing Information for additional Important Safety Information, including most serious side effects, at View Source

About the FDC of Perjeta and Herceptin

The FDC of Perjeta and Herceptin is a new SC formulation that combines pertuzumab and trastuzumab with Halozyme Therapeutics’ Enhanze drug delivery technology.

Trastuzumab in the FDC is the same monoclonal antibody in IV Herceptin, and pertuzumab is the same monoclonal antibody in IV Perjeta. The mechanisms of action of Perjeta and Herceptin are believed to complement each other as both bind to the HER2 receptor, but to different places. The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of the HER signaling pathways.

Halozyme’s Enhanze drug delivery technology may enable and optimize SC drug delivery for appropriate co-administered therapeutics. The technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that temporarily degrades hyaluronan – a glycosaminoglycan or chain of natural sugars in the body, to aid in the dispersion and absorption of other injected therapeutic drugs.

About Kadcyla (ado-trastuzumab emtansine)

Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cancer cells. It is designed to limit damage to healthy tissues, although it can still affect them. Kadcyla can cause serious side effects. It combines two anti-cancer agents using a stable linker: the HER2-targeting trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1. Kadcyla is the only ADC approved for the treatment of HER2-positive metastatic breast cancer. In the U.S., Genentech licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

Important Safety Information

What is the most Important Safety Information I should know about KADCYLA?

Liver problems

KADCYLA may cause severe liver problems that can be life-threatening. Symptoms of liver problems may include vomiting, nausea, eating disorder (anorexia), yellowing of the skin (jaundice), stomach pain, dark urine, or itching
Heart problems

KADCYLA may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure). Symptoms may include swelling of the ankles or legs, shortness of breath, cough, rapid weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness, or irregular heartbeat
Pregnancy

Receiving KADCYLA during pregnancy can result in the death of an unborn baby and birth defects. Birth control should be used while you receive KADCYLA and for 7 months after your last dose of KADCYLA
If you think you may be pregnant, you should contact your healthcare provider immediately
If you are exposed to KADCYLA during pregnancy or if you become pregnant within 7 months following your last dose of KADCYLA, you are encouraged to report KADCYLA exposure to Genentech by calling 1-888-835-2555
If you are a male patient with a female partner that could become pregnant, birth control should be used during treatment and for 4 months following your last dose of KADCYLA
You should not breastfeed during treatment and for 7 months after the last dose of KADCYLA
Contact your doctor right away if you experience symptoms associated with these side effects.

What are the additional possible serious side effects of KADCYLA?

Lung problems

KADCYLA may cause lung problems, including inflammation of the lung tissue, which can be life-threatening. Signs of lung problems may include trouble breathing, cough, tiredness, and fluid in the lungs
Infusion-related reactions

Symptoms of an infusion-related reaction may include one or more of the following: the skin getting hot or red (flushing), chills, fever, trouble breathing, low blood pressure, wheezing, tightening of the muscles in the chest around the airways, or a fast heartbeat. Your doctor will monitor you for infusion-related reactions
Serious bleeding

KADCYLA can cause life-threatening bleeding. Taking KADCYLA with other medications used to thin your blood (antiplatelet) or prevent blood clots (anticoagulation) can increase your risk of bleeding. Your doctor should provide additional monitoring if you are taking one of these other drugs while on KADCYLA. Even when blood thinners are not also being taken, life-threatening bleeding may occur with KADCYLA
Low platelet count

Low platelet count may happen during treatment with KADCYLA. Platelets help your blood to clot. Signs of low platelets may include easy bruising, bleeding, and prolonged bleeding from cuts. In mild cases there may not be any symptoms
Nerve damage

Symptoms may include numbness and tingling, burning or sharp pain, sensitivity to touch, lack of coordination, muscle weakness, or loss of muscle function. Your doctor will monitor you for symptoms of nerve damage
Skin reactions around the infusion site

KADCYLA may leak from the vein or needle and cause reactions such as redness, tenderness, skin irritation, or pain or swelling at the infusion site. If this happens, it is more likely to happen within 24 hours of the infusion
What are the most common side effects of KADCYLA?

The most common side effects in people taking KADCYLA for early breast cancer are:

Tiredness
Nausea
Liver problems
Pain that affects the bones, muscles, ligaments, and tendons
Bleeding
Low platelet count
Headache
Weakness, numbness, and pain in the hands and feet
Joint pain
The most common side effects seen in people taking KADCYLA for metastatic breast cancer are:

Tiredness
Nausea
Pain that affects the bones, muscles, ligaments, and tendons
Bleeding
Low platelet count
Headache
Liver problems
Constipation
Nosebleeds
You are encouraged to report side effects to Genentech and the FDA. You may contact Genentech by calling 1-888-835-2555. You may contact the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.

Talk to a healthcare professional for more information about the benefits and risks of KADCYLA.

Please see full Prescribing Information for Important Safety Information, including Most Serious Side Effects.

About Tecentriq (atezolizumab)

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.

Tecentriq U.S. Indication (pronounced ‘tē-SEN-trik’)

What is Tecentriq?

Tecentriq is a prescription medicine used to treat adults with:

A type of breast cancer called triple-negative breast cancer (TNBC).

Tecentriq may be used with the medicine paclitaxel protein-bound when your breast cancer:

has spread or cannot be removed by surgery, and
your cancer tests positive for "PD-L1."
The approval of Tecentriq in these patients is based on a study that measured the amount of time until patients’ disease worsened. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.

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

Important Safety Information

What is the most important information about Tecentriq?

Tecentriq can cause the immune system to attack normal organs and tissues and can affect the way they work. These problems can sometimes become serious or life threatening and can lead to death.

Patients should call or see their healthcare provider right away if they get any symptoms of the following problems or these symptoms get worse.

Tecentriq can cause serious side effects, including:

Lung problems (pneumonitis)–signs and symptoms of pneumonitis may include new or worsening cough, shortness of breath, and chest pain
Liver problems (hepatitis)–signs and symptoms of hepatitis may include yellowing of the skin or the whites of the eyes, severe nausea or vomiting, pain on the right side of the stomach area (abdomen), drowsiness, dark urine (tea colored), bleeding or bruising more easily than normal, and feeling less hungry than usual
Intestinal problems (colitis)–signs and symptoms of colitis may include diarrhea (loose stools) or more bowel movements than usual, blood or mucus in stools or dark, tarry, sticky stools, and severe stomach area (abdomen) pain or tenderness
Hormone gland problems (especially the thyroid, adrenal glands, pancreas, and pituitary)–signs and symptoms that the hormone glands are not working properly may include headaches that will not go away or unusual headaches, extreme tiredness, weight gain or weight loss, dizziness or fainting, feeling more hungry or thirsty than usual, hair loss, changes in mood or behavior (such as decreased sex drive, irritability, or forgetfulness), feeling cold, constipation, the voice gets deeper, urinating more often than usual, nausea or vomiting, and stomach area (abdomen) pain
Problems in other organs–signs and symptoms may include severe muscle weakness, numbness or tingling in hands or feet, confusion, blurry vision, double vision, or other vision problems, changes in mood or behavior, extreme sensitivity to light, neck stiffness, eye pain or redness, skin blisters or peeling, chest pain, irregular heartbeat, shortness of breath, or swelling of the ankles
Severe infections–signs and symptoms of infection may include fever, cough, flu-like symptoms, pain when urinating, and frequent urination or back pain
Severe infusion reactions–signs and symptoms of infusion reactions may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, swelling of the face or lips, dizziness, fever, feeling like passing out, and back or neck pain
Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may delay or completely stop treatment with Tecentriq if patients have severe side effects.

Before receiving Tecentriq, patients should tell their healthcare provider about all of their medical conditions, including if they:

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 problems; have a condition that affects the nervous system (such as myasthenia gravis or Guillain-Barre syndrome); or are being treated for an infection
are pregnant or plan to become pregnant. Tecentriq can harm an unborn baby. Patients should tell their healthcare provider right away if they become pregnant or think they may be pregnant during treatment with Tecentriq. Females who are able to become pregnant:
A healthcare provider should do a pregnancy test before they start treatment with Tecentriq.
They should use an effective method of birth control during their treatment and for at least 5 months after the last dose of Tecentriq.
are breastfeeding or plan to breastfeed. It is not known if Tecentriq passes into the breast milk. Patients should not breastfeed during treatment and for at least 5 months after the last dose of Tecentriq.
Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Tecentriq when used in triple-negative breast cancer with paclitaxel protein-bound include:

hair loss
tingling or numbness in hands or feet
feeling tired
nausea
diarrhea
low red blood cells (anemia)
constipation
cough
headache
low white blood cells
vomiting
decreased appetite
Tecentriq may cause fertility problems in females, which may affect the ability to have children. Patients should talk to their healthcare provider if they have concerns about fertility.

These are not all the possible side effects of Tecentriq. Patients should ask their healthcare provider or pharmacist for more information. Patients should call their doctor for medical advice about side effects.

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the Tecentriq full Prescribing Information for additional Important Safety Information.

About Genentech in breast cancer

Genentech has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have substantially improved outcomes for HER2-positive breast cancer. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including triple-negative and hormone receptor-positive.

On November 18, 2019 Reata Pharmaceuticals, Inc. (Nasdaq: RETA) ("Reata" or the "Company"), a clinical-stage biopharmaceutical company, reported the closing of its previously announced underwritten public offering of 2,760,000 shares of its Class A common stock, which included 360,000 shares sold pursuant to the underwriters’ full exercise of their option to purchase additional shares, at a price to the public of $183.00 per share (Press release, Reata Pharmaceuticals, NOV 18, 2019, View Source [SID1234551431]). The gross proceeds to Reata from the offering, before deducting underwriting discounts and commissions and other offering expenses, are expected to be approximately $505.1 million.

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!

Citigroup, Jefferies, SVB Leerink and Stifel acted as the joint book-running managers for the offering. Baird, Cantor and Ladenburg Thalmann acted as the co-managers for the offering.

Reata intends to use the net proceeds from the offering for working capital and general corporate purposes, which include, but are not limited to, advancing the development of bardoxolone methyl and omaveloxolone through clinical trials, preparing to file New Drug Applications for bardoxolone for the treatment of patients with Alport syndrome and omaveloxolone for the treatment of patients with Friedreich’s ataxia, planning for commercialization of its potential products, and making payments due under our agreement with AbbVie Inc.

The securities described above were offered pursuant to an automatically effective shelf registration statement on Form S-3 that was filed with the Securities and Exchange Commission (the "SEC") on July 23, 2018. The offering was conducted only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A final prospectus supplement and accompanying prospectus relating to the offering have been filed with the SEC and are available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus may also be obtained by request at Citigroup, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717 (Tel: 800-831-9146); at Jefferies, Attention: Equity Syndicate Prospectus Departments, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by phone at (877) 821-7388, or by email at [email protected]; at SVB Leerink, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at 1-800-808-7525, ext. 6132, or by email at [email protected]; or Stifel, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, CA 94104, or by telephone at (415) 364-2720, or by email at [email protected].

This news release is for informational purposes only and shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities, in any state or jurisdiction in which such offer, solicitation, or sale of these securities would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On November 18, 2019 Oncotelic Inc. ("Oncotelic"), a wholly owned subsidiary of Mateon Therapeutics Inc. (OTCQB:MATN) dedicated to the development of innovative treatments for cancer, reported that it will present data updates regarding the anti-brain tumor activity of its 1st-in class RNA therapeutic OT101 during the upcoming 2019 Society for Neuro-Oncology (SNO) Annual Meeting on November 20-November 24 in Phoenix, Arizona (View Source (Press release, Mateon Therapeutics, NOV 18, 2019, View Source [SID1234551430]).

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!

"We look forward to sharing the latest data on the clinical impact potential of OT101 that will add to the body of evidence supporting its potential as a future treatment option for high-grade glioma patients," said Fatih Uckun, M.D., Ph.D., Chief Medical Officer, Mateon Therapeutics. "These presentations underscore our continued efforts to advance the standard of care and improve treatment expectations for brain tumor patients," added Vuong Trieu, Ph.D, the Chief Executive Officer and President of Mateon Therapeutics.

On November 22, for the first time, the Mateon team will present a poster regarding the predictors of response and treatment outcome. Presentation details:
Abstract #: ATIM-10
Abstract Title: Clinical predictors of response for recurrent/refractory glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA, WHO grade III) patients treated with the anti-TGF ß 2 RNA therapeutic OT-101
Session: Poster Session
Date: Friday November 22, 2019
Presentation Time: 7:30 PM – 9:30 PM

On November 23, Dr. Uckun will give a talk as oral abstract speaker on the comparison between OT101 and the standard chemotherapy drug temozolomide in high-grade anaplastic astrocytoma patients. Presentation details:
Abstract #: ATIM-06
Presentation Title: Treatment of recurrent/refractory (R/R) anaplastic astrocytoma (AA, WHO grade 3) patients with anti-TGFß2 RNA therapeutic OT-101 versus temozolomide is associated with improved overall survival
Session: Concurrent Session 3B: Surgery/Radiation Therapy/CNS Metastasis (3B)
Date: Saturday November 23, 2019
Presentation Time: 1:40 PM – 1:50 PM

Later on November 23, the Mateon team will present a second poster with post-hoc analysis of the single agent efficacy of OT101 with prolonged follow-up results from the G004 Phase 2 clinical study. Presentation details:
Abstract #: ATIM-03
Abstract Title: Anti-TGFß2 RNA therapeutic OT-101 induces durable objective responses in patients with recurrent/refractory (R/R) glioblastoma multiforme (GBM, WHO grade 4) or anaplastic astrocytoma (AA, WHO grade 3)
Session: Poster Session
Date: Saturday November 23, 2019
Presentation Time: 5:00 PM – 7:00 PM

"The durable objective responses achieved in adult patients with recurrent/refractory high-grade gliomas after treatment with our lead anti-TGF beta2 compound OT-101 contribute to our optimism that new treatment strategies leveraging OT101 may favorably change the therapeutic landscape for difficult-to-treat brain tumors with a very poor prognosis," Dr. Uckun explained.

Last month, US Food and Drug Administration (FDA) granted Rare Pediatric Disease Designation for OT101/Trabedersen for the treatment of diffuse intrinsic pontine glioma (DIPG) as a drug for a "rare pediatric disease," as defined in section 529(a)(3) of the Federal Food, Drug, and Cosmetic Act. "Our recently published in silico validation of the TGF beta2 gene product, which is the molecular target for OT101/Trabedersen, as a target for immunotherapy in pediatric high-grade gliomas, especially DIPG, indicates that OT101 may also have future potential for the treatment of pediatric DIPG, an orphan disease with a low survival rate and no established or effective standard of care," explained Dr. Uckun.

Dr. Trieu stated: "There is no standard treatment for progressive DIPG after the failure of radiation therapy and no salvage regimen has been shown to extend survival. Therefore, there is an urgent need for therapeutic innovations for treatment of DIPG. Further development of OT-101 may offer renewed hope for salvage therapy of pediatric DIPG patients who have this rare and fatal disease."