Pivotal Phase III Study Shows Genentech’s Tecentriq Helped People With Early Lung Cancer Live Longer Without Their Disease Returning

On March 22, 2021 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that the Phase III IMpower010 study evaluating Tecentriq (atezolizumab), compared with best supportive care (BSC), met its primary endpoint of disease-free survival (DFS) at the interim analysis (Press release, Genentech, MAR 22, 2021, View Source [SID1234576928]). Tecentriq showed a statistically significant improvement in DFS as adjuvant therapy following surgery and chemotherapy in all randomized Stage II-IIIA populations with non-small cell lung cancer (NSCLC). The magnitude of DFS benefit was particularly pronounced in the PD-L1-positive population.

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Follow-up will continue with planned analyses of DFS in the overall intent-to-treat (ITT) population, which at the time of analysis did not cross the threshold, and overall survival (OS) data, which were immature at the time of interim analysis. Safety for Tecentriq was consistent with its known safety profile and no new safety signals were identified. Results from the IMpower010 study will be presented at an upcoming medical meeting and submitted to health authorities globally, including the U.S. Food and Drug Administration and the European Medicines Agency.

"With these landmark results, Tecentriq has become the first cancer immunotherapy to help many people with resectable early lung cancer live longer without their cancer returning," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "We’re excited by the clinical benefit adjuvant Tecentriq may bring to lung cancer patients, particularly in the PD-L1-positive population. We will submit these data to regulatory authorities as soon as possible."

Tecentriq has previously shown clinically meaningful benefit in various types of lung cancer, with five currently approved indications in the U.S. It was the first approved cancer immunotherapy for front-line treatment of adults with extensive-stage small cell lung cancer (SCLC) in combination with carboplatin and etoposide (chemotherapy), and also has four approved indications in NSCLC as either a single agent or in combination with targeted therapies and/or chemotherapies. Tecentriq is available in three dosing options, providing the flexibility to choose administration every two, three or four weeks.

Genentech has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies across different lung, genitourinary, skin, breast, gastrointestinal, gynecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines, as well as studies in metastatic, adjuvant and neoadjuvant settings across various tumor types.

About the IMpower010 study

IMpower010 is a Phase III, global, multicenter, open-label, randomized study evaluating the efficacy and safety of Tecentriq compared with BSC, in participants with Stage IB-IIIA NSCLC (UICC 7th edition), following surgical resection and up to 4 cycles of adjuvant cisplatin-based chemotherapy. The study randomized 1,005 people with a ratio of 1:1 to receive either at most 16 cycles of Tecentriq or BSC. The primary endpoint is investigator-determined DFS in the PD-L1-positive Stage II-IIIA, all randomized Stage II-IIIA and ITT Stage IB-IIIA populations. Key secondary endpoints include OS in the overall study population, ITT Stage IB-IIIA NSCLC.

About lung cancer

According to the American Cancer Society, it is estimated that more than 235,000 Americans will be diagnosed with lung cancer in 2021, and NSCLC accounts for 80-85% of all lung cancers. Today, about half of all people with early lung cancer still experience a cancer recurrence following surgery. Treating lung cancer early, before it has spread, may help prevent the disease from returning and provide people with the best opportunity for a cure.

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. Indications

Tecentriq is a prescription medicine used to treat adults with:

A type of lung cancer called non-small cell lung cancer (NSCLC).

Tecentriq may be used alone as their first treatment when their lung cancer:
has spread or grown, and
their cancer tests positive for "high PD-L1", and
their tumor does not have an abnormal "EGFR" or "ALK" gene
Tecentriq may be used with the medicines bevacizumab, paclitaxel, and carboplatin as their first treatment when their lung cancer:
has spread or grown, and
is a type called "non-squamous NSCLC," and
their tumor does not have an abnormal "EGFR" or "ALK" gene
Tecentriq may be used with the medicines paclitaxel protein-bound and carboplatin as their first treatment when their lung cancer:
has spread or grown, and
is a type called "non-squamous NSCLC," and
their tumor does not have an abnormal "EGFR" or "ALK" gene
Tecentriq may also be used when their lung cancer:
has spread or grown, and
they have tried chemotherapy that contains platinum, and it did not work or is no longer working
if their tumor has an abnormal "EGFR" or "ALK" gene, they should have also tried an FDA-approved therapy for tumors with these abnormal genes, and it did not work or is no longer working
A type of lung cancer called small cell lung cancer (SCLC).

Tecentriq may be used with the chemotherapy medicines carboplatin and etoposide as their first treatment when their lung cancer:
is a type called "extensive-stage small cell lung cancer," which means that it has spread or grown
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 in any area of the body and can affect the way they work. These problems can sometimes become severe or life threatening and can lead to death. Patients can have more than one of these problems at the same time. These problems may happen anytime during their treatment or even after their treatment has ended.

Patients should call or see their healthcare provider right away if they develop any new or worse signs or symptoms, including:

Lung problems

cough
shortness of breath
chest pain
Intestinal problems

diarrhea (loose stools) or more frequent bowel movements than usual
stools that are black, tarry, sticky, or have blood or mucus
severe stomach-area (abdomen) pain or tenderness
Liver problems

yellowing of the skin or the whites of the eyes
severe nausea or vomiting
pain on the right side of their stomach area (abdomen)
dark urine (tea colored)
bleeding or bruising more easily than normal
Hormone gland problems

headaches that will not go away or unusual headaches
eye sensitivity to light
eye problems
rapid heartbeat
increased sweating
extreme tiredness
weight gain or weight loss
feeling more hungry or thirsty than usual
urinating more often than usual
hair loss
feeling cold
constipation
their voice gets deeper
dizziness or fainting
changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems

decrease in their amount of urine
blood in their urine
swelling of their ankles
loss of appetite
Skin problems

rash
itching
skin blistering or peeling
painful sores or ulcers in mouth or nose, throat, or genital area
fever or flu-like symptoms
swollen lymph nodes
Problems can also happen in other organs.

These are not all of the signs and symptoms of immune system problems that can happen with Tecentriq. Patients should call or see their healthcare provider right away for any new or worse signs or symptoms, including:

Chest pain, irregular heartbeat, shortness of breath, or swelling of ankles
Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
Persistent or severe muscle pain or weakness, muscle cramps
Low red blood cells, bruising
Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include:

chills or shaking
itching or rash
flushing
shortness of breath or wheezing
dizziness
feeling like passing out
fever
back or neck pain
Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if patients undergo transplantation either before or after being treated with Tecentriq. A healthcare provider will monitor for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. A healthcare provider will check patients for these problems during their treatment with Tecentriq. A healthcare provider may treat patients with corticosteroid or hormone replacement medicines. A healthcare provider may also need to 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 received an organ transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have received radiation treatment to their chest area
have a condition that affects their nervous system, such as myasthenia gravis or Guillain-Barré syndrome
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 alone include:

feeling tired or weak
nausea
cough
shortness of breath
decreased appetite
The most common side effects of Tecentriq when used in lung cancer with other anti-cancer medicines include:

feeling tired or weak
nausea
hair loss
constipation
diarrhea
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 about the benefits and side effects of Tecentriq.

Report side effects to the FDA at 1-800-FDA-1088 or View Source

Report side effects to Genentech at 1-888-835-2555.

Please see View Source for full Prescribing Information and additional Important Safety Information.

About Genentech in cancer immunotherapy

Genentech has been developing medicines to redefine treatment in oncology for more than 35 years, and today, realizing the full potential of cancer immunotherapy is a major area of focus. With more than 20 immunotherapy molecules in development, Genentech is investigating the potential benefits of immunotherapy alone, and in combination with various chemotherapies, targeted therapies and other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system.

In addition to Genentech’s approved PD-L1 checkpoint inhibitor, the company’s broad cancer immunotherapy pipeline includes other checkpoint inhibitors, individualized neoantigen therapies and T cell bispecific antibodies. For more information visit View Source

About Genentech in lung cancer

Lung cancer is a major area of focus and investment for Genentech, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have five approved medicines to treat certain kinds of lung cancer and more than 10 medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

Entry into a Material Definitive Agreement

On March 21, 2021, Aeglea BioTherapeutics, Inc. (the "Company") reported that it entered into a license and supply agreement (the "License Agreement") with Immedica Pharma AB ("Immedica"), pursuant to which Immedica licensed the product rights for commercialization of pegzilarginase in the European Economic Area, United Kingdom, Switzerland, Andorra, Monaco, San Marino, Vatican City, Turkey, Saudi Arabia, United Arab Emirates, Qatar, Kuwait, Bahrain, and Oman. Upon signing, the Company is entitled to an upfront payment of $21.5 million from Immedica (Filing, 8-K, Aeglea BioTherapeutics, MAR 21, 2021, View Source [SID1234576942]). Under the terms of the License Agreement, the Company is eligible to receive aggregate regulatory and commercial milestone payments of up to approximately $130.0 million. Additionally, the Company is entitled to receive royalties in the mid-20 percent range on net sales of the product in certain countries that may result from the License Agreement. The Company will continue to be responsible for certain clinical development activities and the manufacturing of pegzilarginase and will retain commercialization rights in the U.S. and rest of the world.

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Antengene to Present Preclinical Data Demonstrating the Synergistic Effect of the Combination of XPO1 and mTORC1/2 Inhibition for the Treatment of Triple-Hit DLBCL at AACR Annual Meeting 2021

On March 21, 2021 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing, and commercializing global first-in-class and/or best-in-class therapeutics in hematology and oncology, reported that it will present the preclinical data on the synergistic effect of the combination of XPO1 and mTORC1/2 inhibition for the treatment of triple-hit diffuse large B-cell lymphoma (DLBCL) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, which will be held in a virtual format on April 10-15 and May 17-21, 2021 (Press release, Antengene, MAR 21, 2021, View Source [SID1234576930]).

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Title: Synergistic effect of the combination of XPO1 and mTORC1/2 inhibition for the treatment of triple-hit DLBCL
Permanent Abstract Number: 1380
Abstract Link: View Source!/9325/presentation/2406

Covering the most cutting-edge advances and regarded globally as the very pinnacle of cancer research, the AACR (Free AACR Whitepaper) Annual Meeting is one of the largest and most anticipated scientific events in the cancer research field globally. The abstract entitled "Synergistic effect of the combination of XPO1 and mTORC1/2 inhibition for the treatment of triple-hit DLBCL" now available on the AACR (Free AACR Whitepaper)’s website, is the first publication from the preclinical study investigating ATG-010 (XPO1 inhibitor) and ATG-008 (mTORC1/2 inhibitor).

ATG-010, also known as selinexor, is the world’s first approved selective inhibitor of the nuclear export protein XPO1. ATG-010 induces the apoptosis of cancer cells in vitro and in vivo through the targeted inhibition of the nuclear export protein XPO1 that leads to the nuclear storage and activation of tumor-suppressor proteins and other growth-regulating proteins, and by down-regulating the intracytoplasmic levels of various oncogenic proteins without affecting normal cells.

ATG-008, also known as onatasertib, is a next-generation dual mTORC1/2 inhibitor. mTORC1 and mTORC2 are critical mediators of the PI3K-AKT pathway, which is commonly mutated in many cancers, thus leading to the hyperactivation of mTOR signaling. ATG-008 could reduce the proliferation and promote the apoptosis of tumor cells through the dual-inhibition of mTORC1 and mTORC2.

ATG-010 (selinexor) is approved in the U.S. and Israel for the treatment of multiple myeloma (MM) and DLBCL, and has been included in five treatment regimens by the National Comprehensive Cancer Network (NCCN) Guidelines. Multiple clinical studies have shown that the special mechanism of action (MoA) of ATG-010 allows the drug candidate the therapeutic utility in combination with a variety of antitumor drugs, such as anti-PD-L1 antibodies, for improved efficacy and reduction in treatment-related adverse events. Other studies carried out by Antengene also showed that the dual-inhibition of XPO1 and mTOR has the effect of bolstering antitumor activities.

At present, Antengene is conducting several trials of ATG-010 in China for the treatment of MM, DLBCL, non-small cell lung cancer (NSCLC), endometrial cancer, peripheral T-cell lymphoma and NK/T cells lymphoma. Furthermore, Antengene has submitted New Drug Applications (NDAs) for ATG-010 in multiple APAC markets including China, Australia, Singapore and South Korea. Meanwhile, Antengene has also initiated several clinical trials of ATG-008 in China and other APAC markets for the treatment of advanced hepatocellular carcinoma (HCC), advanced NSCLC, advanced solid tumors harboring NFE2L2, STK11, RICTOR or other specific genetic alterations, and in combination with an anti-PD-1 antibody in advanced solid tumors including HCC.

Harbour BioMed Announces Dosing of First Patient in Phase I Clinical Study of its Next-Generation Anti-CTLA-4 Antibody in China

On March 21, 2021 Harbour BioMed (HBM) (HKEX: 02142) reported the dosing of the first patient in its open Phase I clinical study of HBM4003 for Chinese patients suffering from advanced melanoma and other solid tumors (study No. 4003.2) (Press release, Harbor BioSciences, MAR 21, 2021, View Source [SID1234576929]). This study will evaluate the safety, tolerability, PK/PD, and anti-tumor activity of HBM4003 in combination with teriprizumab (PD-1 antibody) in the treatment of solid tumors. Prior to this, the China National Medical Products Administration (NMPA) has approved this combined study of HBM4003 and PD-1 antibody/chemotherapy for patients with NSCLC and other solid tumors.

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Professor Jun Guo, Deputy Dean of Beijing Cancer Hospital, Deputy Director of Beijing Institute for Cancer Research and Director of Melanoma Department, said: "Due to the special subtype of melanoma in China, treatment for this disease is especially challenging, resulting from poor prognosis, low survival rate, and the limited efficacy of current PD-1 monotherapy of around 16 percent. Innovative solutions that can improve the treatment efficacy and patients’ overall survival is urgently needed. As this study by Harbour BioMed unfolds, we look forward to providing more effective and safer treatment options to Chinese patients with melanoma and other solid tumors in a near future."

"HBM4003 is a new generation of anti-CTLA-4 antibody. Based on its unique mechanism, it has shown great safety and strong anti-tumor activity in pre-clinical studies." Dr. Wang Jingsong, Founder, Chairman and CEO of Harbour BioMed said. "Each year, there are about 4 million newly diagnosed cancer patients in China and there is an urgent need for innovative drugs and therapeutic solutions for cancer treatment. We will continue to accelerate the global development of HBM4003 for multiple cancers, so that we can help cancer patients around the world to live better and longer lives."

About HBM4003

HBM4003 is the fully human anti-CTLA-4 monoclonal heavy chain only antibody (HCAb) generated from Harbour Mice. HBM4003 shows enhanced antibody-dependent cell cytotoxicity (ADCC) killing activity and is extremely specific to high CTLA-4 Treg cells in tumor tissues. The potent anti-tumor efficacy and differentiated pharmacokinetics with durable pharmacodynamic effect presents a favorable product profile. This novel and differentiated mechanism of action has the potential to improve efficacy while significantly reducing the toxicity of the drug.

Announcement of Research Collaboration with Daiichi-Sankyo

On March 19, 2021 Optieum Biotechnologies reported that the company has entered into a research collaboration with Daiichi Sankyo Company (Press release, Optieum Biotechnologies, MAR 19, 2021, https://optieumbio.com/wp-content/uploads/2021/03/20210319_Announcement-of-Research-Collaboration-with-Daiichi-Sankyo.pdf [SID1234639139]). Optieum Biotechnologies intends to use its Eumbody System technology to identify a new functional single chain fragment variables (scFvs) that can be utilized for CAR-T cell against the target of interest selected by Daiichi Sankyo.

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Eumbody System is a single-chain antibody generation system yielding CAR-T cells with superior antitumor function developed by Dr. Toshiki Ochi, co-founder of Optieum Biotechnologies, which exclusive license is granted to Optieum Biotechnologies.

Under the terms of the agreement, Optieum Biotechnologies will receive an undisclosed upfront payment, and is eligible for payments associated with the achievement of certain development milestones.