On June 29, 2020 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported that the U.S. Food and Drug Administration (FDA) has approved Roche’s Phesgo (pertuzumab, trastuzumab, and hyaluronidase-zzxf) injection, a fixed-dose combination (FDC) of Perjeta and Herceptin with Halozyme’s ENHANZE technology, administered subcutaneously in combination with intravenous (IV) chemotherapy, for the treatment of eligible patients with early and metastatic HER2-positive breast cancer (Press release, Halozyme, JUN 29, 2020, View Source [SID1234561532]). This is the first time a product has been approved combining two monoclonal antibodies that can be administered by a single subcutaneous injection utilizing Halozyme’s ENHANZE technology.

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 are excited that HER2-positive breast cancer patients in the U.S. will now have the option to receive this important therapy in a meaningfully shorter period of time," said Dr. Helen Torley, president and chief executive officer. "This subcutaneous delivery was shown to be preferred to IV administration by 85% of patients in the PHranceSCa study due to less time in the clinic and more comfortable treatment administration. Phesgo is the second product to receive FDA approval this year, and the first demonstrating the ability to combine two monoclonal antibodies, utilizing our ENHANZE technology."

Phesgo is available in single-dose vials and can be administered in approximately eight minutes for the initial loading dose and approximately five minutes for each subsequent maintenance dose.(1) This is compared to approximately 150 minutes for a sequential infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60-150 minutes for subsequent maintenance infusions of the two medicines.(2,3) Phesgo can be administered by a healthcare professional in a treatment center or at a patient’s home.

The approval is based on results from the pivotal phase III FeDeriCa study, which met its primary endpoint, with Phesgo showing non-inferior levels of Perjeta in the blood during a given dosing interval (Ctrough), when compared to IV administration of Perjeta. The safety profile of Phesgo with chemotherapy was comparable to IV administration of Perjeta plus Herceptin and chemotherapy, and no new safety signals were identified, including no meaningful difference in cardiac toxicity. The most common adverse events in both arms were alopecia, nausea, diarrhea and anemia.(1,4)

The phase II PHranceSCa study showed that 85% (136/160) of people receiving treatment for HER2-positive breast cancer preferred treatment under the skin to IV administration due to less time in the clinic and more comfortable treatment administration.(1)

About ENHANZE Technology
Halozyme’s proprietary ENHANZE drug-delivery technology is based on its patented recombinant human hyaluronidase enzyme (rHuPH20). rHuPH20 has been shown to remove traditional limitations on the volume of biologics that can be delivered subcutaneously (just under the skin). By using rHuPH20, some biologics and compounds that are administered intravenously may instead be delivered subcutaneously. ENHANZE may also benefit subcutaneous biologics by reducing the need for multiple injections. This delivery has been shown in studies to reduce health care practitioner time required for administration and shorten time for drug administration.

On June 29, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported that The Lancet Oncology published data from the NAVIGATOR clinical trial showing an unprecedented overall survival (OS) rate and a well-tolerated safety profile for AYVAKIT (avapritinib) in patients with advanced PDGFRA D842V mutant gastrointestinal stromal tumor (GIST) (Press release, Blueprint Medicines, JUN 29, 2020, View Source [SID1234561548]). The paper, titled "Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial," was published online in The Lancet Oncology on June 29, 2020.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The data published in The Lancet Oncology show that patients with PDGFRA D842V mutant GIST treated with AYVAKIT had deep and durable clinical responses as well as a high overall survival rate. These results represent a transformative advancement for patients whose tumor type is resistant to other approved therapies," said Michael Heinrich, M.D., Professor of Medicine at Oregon Health & Science University and primary author of the paper. "As a scientist who has dedicated my career to understanding the molecular basis of GIST and as a clinician treating patients, it’s tremendously rewarding to be able to offer – for the first time – a highly effective treatment option to my patients with PDGFRA D842V mutant GIST."

"Based on the compelling clinical data from the NAVIGATOR trial, AYVAKIT was granted a full approval by the FDA earlier this year and has become the new standard of care for patients with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "We are now focused on bringing AYVAKIT to additional patients with this genomically defined form of GIST in other geographies, including Europe."

Highlights from The Lancet Oncology Publication Data

The Lancet Oncology paper reported efficacy and safety results from the NAVIGATOR trial, including all patients enrolled in the dose escalation part of the trial and the subset of patients with PDGFRA D842V mutant GIST enrolled in the expansion part of the trial. The efficacy population comprised 56 patients with PDGFRA D842V mutant GIST. The safety population comprised 82 patients, including 26 patients with non-PDGFRA D842V mutant GIST enrolled in the dose escalation part of the trial. All results were as of a data cutoff date of November 16, 2018.

In patients with PDGFRA D842V mutant GIST, the overall response rate (ORR) was 88 percent (95% CI: 76-95%) with 9 percent of patients achieving a complete response. AYVAKIT demonstrated durable clinical benefit in this patient population with a 12-month duration of response rate of 70 percent (95% CI: 54-87%), a 12-month progression-free survival (PFS) rate of 81 percent (95% CI: 69-93%) and a 24-month OS rate of 81 percent (95% CI: 67-94%).

AYVAKIT was generally well-tolerated with most treatment-related adverse events (AEs) reported as Grade 1 or 2. The most common treatment-related AEs were nausea, fatigue, diarrhea, periorbital edema, anemia, decreased appetite, vomiting and memory impairment. Cognitive effects occurred in 40 percent of patients, with the majority of events reported as Grade 1.

About AYVAKIT (avapritinib)

AYVAKIT (avapritinib) is a kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. AYVAKIT is the first precision therapy approved to treat a genomically defined population of patients with GIST and the only highly active treatment for PDGFRA exon 18 mutant GIST. The FDA granted Breakthrough Therapy Designation to avapritinib for the treatment of unresectable or metastatic GIST harboring the PDGFRA D842V mutation. For more information, visit AYVAKIT.com.

Avapritinib is not approved for the treatment of any other indication in the U.S. by the FDA or for any indication in any other jurisdiction by any other health authority.

Blueprint Medicines is developing avapritinib globally for the treatment of advanced, smoldering and indolent systemic mastocytosis (SM). The FDA granted Breakthrough Therapy Designation to avapritinib for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.

About GIST

GIST is a sarcoma, or tumor of bone or connective tissue, of the GI tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50 to 80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction.

About 5 to 6 percent of primary GIST cases are caused by a PDGFRA D842V mutation, the most common PDGFRA exon 18 mutation. Prior to the approval of AYVAKIT, there were no highly effective treatments for PDGFRA D842V mutant GIST. Published data have shown poor outcomes in patients with PDGFRA D842V mutant GIST treated with imatinib and other approved therapies, including a median OS of 15 months, a median PFS of 3 months and an ORR of 0 percent.1

Important Safety Information

Intracranial hemorrhage (e.g., subdural hematoma, intracranial hemorrhage, and cerebral hemorrhage) occurred in 1% of 267 patients (0.7% Grade 3 or 4) with GIST and overall in 3% of 335 patients (1.2% Grade 3 or 4) who received AYVAKIT. Overall, 0.9% of patients receiving AYVAKIT required permanent discontinuation for an intracranial hemorrhage. Withhold AYVAKIT and then resume at a reduced dose upon resolution, or permanently discontinue AYVAKIT based on severity.

In 335 patients receiving AYVAKIT, CNS adverse reactions occurred overall in 58% of patients including cognitive impairment (41%; 3.6% Grade 3 or 4), dizziness (20%; 0.6% Grade 3 or 4), sleep disorders (15%; 0.3% Grade 3 or 4), mood disorders (13%; 1.5% Grade 3 or 4), speech disorders (6%; none Grade 3 or 4), and hallucinations (2.1%; none Grade 3 or 4). Overall, 3.9% of patients required permanent discontinuation of AYVAKIT for a CNS adverse reaction. Depending on severity, withhold AYVAKIT and then resume at the same dose or at a reduced dose upon improvement, or permanently discontinue AYVAKIT.

AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential and pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective method of contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for two weeks after the final dose. Advise females and males of reproductive potential that AYVAKIT may impair fertility.

In 204 patients with unresectable or metastatic GIST, the most common adverse reactions (≥ 20%) were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash and dizziness.

Avoid coadministration of AYVAKIT with strong and moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong and moderate CYP3A inducers.

Please click here to see the full Prescribing Information for AYVAKIT.

On June 29, 2020 Boryung Pharmaceutical is developing BR101801 (project name BR2002) is an anti-cancer drug which simultaneously inhibits PI3K (γ/δ) and DNA-PK, showed its potential as a treatment in various solid cancer models as well as in blood cancer (Press release, Boryung Pharmaceutical, JUN 29, 2020, View Source [SID1234644864]).

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!

Boryung Pharmaceutical unveiled some of the pre-clinical trial results of BR101801 at the annual conference of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), which was held online on the 22nd (local time).

PI3K (phosphoinositide3-kinase) is an enzyme that regulates intracellular signal transduction process and regulates multiple functions such as cell growth, proliferation and differentiation, migration, and survival. As an enzyme that recognizes and repairs DNA damage in cells, DNA-PK helps cancer cells survive despite of DNA damage.

BR101801, solely developed by Boryung Pharmaceutical, is a target anti-cancer agent and cancer immunotherapy agent that simultaneously inhibits PI3K and DNA-PK. In this AACR (Free AACR Whitepaper), Boryung Pharmaceutical released total of 3 posters of which are related to cancer cell death of BR101801: efficacy in monotherapy and combined therapy, efficacy as an cancer immunotherapy drug, ability to inhibit repair factor of cancer cell damage.

Boryung Pharmaceutical not only uses BR101801 alone but also BR101801+ anti PD-1, BR101801+ anti PD-L1, BR101801+ OX40, BR101801+ Doxorubicin in various animal models such as liver cancer, breast cancer, lung cancer and colon cancer models. As a result of combination therapy, efficacy of BR101801 in terms of survival rate and tumor size was confirmed as compared with the control group.

Boryung Pharmaceutical has also conducted a mono and combined efficacy study of BR101801 on cancer cell deaths from peripheral blood mononuclear cells (human PBMCs). Gilead’s Zydelig (Idelalisib), Verastem’s Copiktra (Duvelisib) and other drugs that have been approved as PI3K inhibitors to date have been set as a control group for comparative studies. As a result, it was confirmed that BR101801 showed superior efficacy in killing cancer cells and controlling c-Myc (tumor-inducing gene) compared to the controls from 52 hematological cancer cell lines.

Especially when BR101801 alone is administered, Treg (regulatory T cells) and MDSC (bone marrow-derived suppressor cells), which are immunosuppressive cells, are decreased, and CD8+, which is an immune cell that kills cancer cells, is increased. It has confirmed its effects of a cancer immunotherapy agent. Also, it showed the effect of inhibiting DNA-PK, which is an enzyme involved in recognizing DNA damage in cancer cells and involved in repair, and showed the effect of killing cancer cells.

The researcher team said, "BR101801 has been shown to have the effect of killing cancer cells not only in blood cancer but also in various solid cancers when co-administered with cytotoxic anti-cancer drug or through the radiation."

Boryung Pharmaceutical said BR101801 has been currently undergoing 1st clinical phase for the indication of non-Hochkin’s lymphoma, a type of blood cancer, simultaneously in Korea and in the U.S. since this March.

On June 29, 2020 Oblique Therapeutics reported that it has entered into a collaboration agreement with Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing oncolytic viruses to target hard-to-treat solid tumors, to evaluate the potential of using ONCOS oncolytic adenoviruses as a vector to encode and deliver AbiprotTM antibodies against hard-to-reach intra-cellular targets (Press release, Oblique Therapeutics, JUN 29, 2020, View Source [SID1234561512]).

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!

Oblique Therapeutics has developed a unique, proprietary methodology to identify epitopes on targets that have previously proven difficult to address with antibodies. This approach can be extended to intra-cellular targets such as mutant RAS, however, delivering antibodies into cells remains a major obstacle.Oblique Therapeutics and Targovax anticipate that expression of AbiprotTM antibodies against such targets using ONCOS as a vector can overcome this challenge and boost the specificity and power of the anti-tumor response.

Under the agreement the parties will jointly explore the technical feasibility and in vitro and in vivo functionality and anti-cancer activity of the ONCOS-Abiprot combination, initially focusing on mutant RAS as the target. If successful, this would provide a first-in-class oncolytic virus candidate directly targeting RAS and demonstrate proof-of-concept for ONCOS-AbiprotTM as a new technology platform.

Dr. Sreesha P Srinivasa, Ph.D., Senior Vice President, Translational R&D Oblique Therapeutics, commented, "We are delighted to partner with Targovax in extending the capabilities of our proprietary AbiprotTM platform to translate antibodies against difficult to reach intra-cellular targets into effective therapeutics. RAS is one of the most frequently mutated oncogenes but has until recently proven to be therapeutically intractable. Oblique has used its AbiprotTM platform to identify novel epitopes on mutant RAS and developed functional antibodies against these epitopes. The ONCOS platform potentially offers an efficient vehicle for intracellular delivery of these functional antibodies into cancer cells. If proven successful, this extends the target space addressable by antibodies to a large number of very important intracellular oncogenes"

Dr. Victor Levitsky, Ph.D., Chief Scientific Officer of Targovax, said: "We continue to explore innovative strategies to expand our ONCOS platform into mutant RAS immunotherapy, and we are very excited to initiate this collaboration with our colleagues at Oblique Therapeutics. With AbiprotTM they have built a cutting-edge methodology to develop antibodies against historically difficult targets to address, such as mutant RAS. By employing ONCOS as a vector for Oblique’s antibodies we believe we can both enhance antibody delivery into cancer cells and strengthen the oncolytic power of the ONCOS virus, and thus drive a synergistic effect between the two modalities"

On June 29, 2020 The U.S. Food and Drug Administration approved Keytruda (pembrolizumab) for intravenous injection for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (Press release, US FDA, JUN 29, 2020, View Source [SID1234561533]). This marks the first immunotherapy approved for this patient population as a first-line treatment and which is administered to patients without also giving chemotherapy.

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!

MSI-H and dMMR tumors contain abnormalities that affect the proper repair of DNA inside the cell. The frequency of MSI-H varies across tumor types and stages, and approximately 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors.

"Metastatic colorectal cancer is a serious and life-threatening disease with a poor prognosis. Available current therapy with chemotherapy combinations and other biologics are associated with substantial toxicity," said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. "Having a non-chemotherapy option available for selected patients is a noteworthy paradigm shift in treatment."

Keytruda works by targeting the cellular pathway of proteins found on the body’s immune cells and some cancer cells, known as PD-1/PD-L1. By blocking this pathway, Keytruda may help the body’s immune system fight the cancer cells and provide a benefit in patients with MSI-H or dMMR metastatic colorectal cancer. The FDA previously approved Keytruda to treat other types of cancer.

The FDA’s approval for this indication was based on the results of one multicenter, international, open-label, active-controlled, randomized trial that compared Keytruda with chemotherapy treatment in 307 patients with MSI-H or dMMR metastatic colorectal cancer. The study demonstrated a statistically significant improvement in progression-free survival (PFS) as assessed by blinded independent review. Median PFS was 16.5 months in the Keytruda group and 8.2 months in the standard of care group. Longer-term analysis is needed to assess for an effect on survival.

Common side effects of Keytruda include fatigue, musculoskeletal pain, decreased appetite, itchy skin (pruritus), diarrhea, nausea, rash, fever (pyrexia), cough, difficulty breathing (dyspnea), constipation, pain, and abdominal pain. Keytruda can cause serious conditions known as immune-mediated side effects, including inflammation of healthy organs such as the lungs (pneumonitis), colon (colitis), liver (hepatitis), endocrine glands (endocrinopathies) and kidneys (nephritis). Patients who experience severe or life-threatening infusion-related reactions should stop taking Keytruda. Women who are pregnant should be advised that Keytruda may cause harm to a developing fetus. Women who are breastfeeding should not take Keytruda because it may cause harm to a breastfed child.

The FDA granted this application Priority Review, which directs overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. This review also used the Real-Time Oncology Review, which streamlines data submission prior to the filing of the entire marketing application, the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment of an application, and Summary Level Review, which allows FDA to rely on qualified data summaries to support approval of a supplemental application. The FDA collaborated with international agency counterparts on the review of this application as part of Project Orbis.

The FDA granted this approval of Keytruda to Merck & Co.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.