On December 10, 2019 Amgen (NASDAQ:AMGN) reported additional results from the primary analysis of the Phase 3 CANDOR study evaluating KYPROLIS (carfilzomib) in combination with dexamethasone and DARZALEX (daratumumab) (KdD) compared to KYPROLIS and dexamethasone alone (Kd) in patients with relapsed or refractory multiple myeloma (Press release, Amgen, DEC 10, 2019, View Source [SID1234552218]). The data will be presented in a late-breaking abstract session at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition.

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!

At a median follow up of 17 months, the study met its primary endpoint of progression-free survival (PFS), resulting in a 37% reduction in the risk of disease progression or death in patients receiving KdD (HR=0.63; 95% CI: 0.464, 0.854; p=0.0014). Median PFS was not reached for the KdD arm versus 15.8 months for the Kd arm.

"This primary analysis of the CANDOR study adds to the body of evidence supporting the combination of KYPROLIS and DARZALEX, two powerful targeted agents for multiple myeloma," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "KYPROLIS has demonstrated deep and sustained responses in treating patients with multiple myeloma that have relapsed. The CANDOR study now offers additional insight into the effectiveness of this combination as a potential new treatment option for relapsed myeloma patients."

In addition to meeting the primary endpoint, the KdD combination demonstrated efficacy in key secondary endpoints, including overall response rate (ORR), minimal residual disease (MRD) negative-complete response at 12 months and overall survival (OS). The ORR was 84.3% versus 74.7% (p=0.0040), and the rate of complete response or better was 28.5% versus 10.4% for the KdD and Kd arms, respectively. The analysis found the MRD-negative complete response rate at 12 months was 12.5% for KdD versus 1.3% for Kd (p<0.0001), a nearly 10-times higher response rate versus Kd-treated patients. The median OS was not reached in either group (HR=0.75; 95% CI: 0.49, 1.13; p=0.08).

"With the increasing use of frontline lenalidomide based therapies, there is an emerging need for lenalidomide-sparing regimens at relapse," said Saad Usmani, M.D., chief of the Plasma Cell Disorders Division and the director of Clinical Research in Hematologic Malignancies, Atrium Health’s Levine Cancer Institute (LCI). "The CANDOR trial demonstrates the potential efficacy of a lenalidomide-sparing regimen that combines two effective targeted agents and provides deep and durable responses upon relapse."

The safety of KdD was consistent with the known safety profiles of the individual agents. The most frequently reported (≥ 20% of subjects in either treatment arm [KdD, Kd]) treatment emergent adverse events included thrombocytopenia, anemia, diarrhea, hypertension upper respiratory tract infection, fatigue, and dyspnea. The incidence of treatment emergent grade 3 or higher, serious, and fatal adverse events was higher in the KdD arm compared to the Kd arm. The rate of treatment discontinuation due to AEs was similar in both arms.

Additional efficacy endpoints and key subgroup analyses will be presented at future meetings.

About CANDOR
CANDOR, a randomized, open-label Phase 3 study of KYPROLIS, dexamethasone and DARZALEX (KdD) compared to KYPROLIS and dexamethasone (Kd), evaluated 466 relapsed or refractory multiple myeloma patients who have received one to three prior therapies. Patients were treated until disease progression. The primary endpoint was PFS, and the key secondary endpoints were overall response rate, minimal residual disease and overall survival. PFS was defined as time from randomization until disease progression or death from any cause.

In the first arm, patients received KYPROLIS twice weekly at 56 mg/m2 and dexamethasone in combination with DARZALEX. In the second arm (control), patients received KYPROLIS twice weekly at 56 mg/m2 and dexamethasone.

CANDOR was initiated as part of a collaboration with Janssen, and under the terms of the agreement, Janssen co-funded the study. For more information about this trial, please visit www.clinicaltrials.gov under trial identification number NCT03158688.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.1 It is a rare and life-threatening disease that accounts for approximately one percent of all cancers.2,3 Worldwide, approximately 160,000 people are diagnosed with multiple myeloma each year, and 106,000 patient deaths are reported on an annual basis.2

About KYPROLIS (carfilzomib)
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.4 KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.5 In some cells, KYPROLIS can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.4,5

Since its first approval in 2012, approximately 130,000 patients worldwide have received KYPROLIS. KYPROLIS is approved in the U.S. for the following:

In combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy
As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy
KYPROLIS is also approved in Algeria, Argentina, Australia, Bahrain, Belarus, Brazil, Canada, Chile, Colombia, Ecuador, Egypt, European Union, Hong Kong, India, Israel, Japan, Jordan, Kuwait, Lebanon, Macao, Malaysia, Mexico, Morocco, New Zealand, Oman, Peru, Philippines, Qatar, Russia, Saudi Arabia, Singapore, S. Korea, Switzerland, Taiwan, Thailand, Turkey and United Arab Emirates.

Important U.S. KYPROLIS (carfilzomib) Safety Information

Cardiac Toxicities

New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of administration.
Monitor patients for signs or symptoms of cardiac failure or ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart at 1 dose level reduction based on a benefit/risk assessment.
While adequate hydration is required prior to each dose in Cycle 1, monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate.
For patients ≥ 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment prior to starting treatment with KYPROLIS and remain under close follow-up with fluid management.
Acute Renal Failure

Cases of acute renal failure, including some fatal renal failure events, and renal insufficiency adverse events (including renal failure) have occurred. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.
Tumor Lysis Syndrome

Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred. Patients with a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly, and withhold until resolved.
Pulmonary Toxicity

Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred. Some events have been fatal. In the event of drug‐induced pulmonary toxicity, discontinue KYPROLIS.
Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) was reported. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS for PAH until resolved or returned to baseline and consider whether to restart based on a benefit/risk assessment.
Dyspnea

Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart based on a benefit/risk assessment.
Hypertension

Hypertension, including hypertensive crisis and hypertensive emergency, has been observed, some fatal. Control hypertension prior to starting KYPROLIS. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS and evaluate. Consider whether to restart based on a benefit/risk assessment.
Venous Thrombosis

Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed. Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.
Patients using hormonal contraception associated with a risk of thrombosis should consider an alternative method of effective contraception during treatment.
Infusion Reactions

Infusion reactions, including life‐threatening reactions, have occurred. Signs and symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, laryngeal edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration. Pre-medicate with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risk and of symptoms and seek immediate medical attention if they occur.
Hemorrhage

Fatal or serious cases of hemorrhage have been reported. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate.
Thrombocytopenia

KYPROLIS causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Monitor platelet counts frequently during treatment. Reduce or withhold dose as appropriate.
Hepatic Toxicity and Hepatic Failure

Cases of hepatic failure, including fatal cases, have occurred. KYPROLIS can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate.
Thrombotic Microangiopathy

Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome have occurred. Monitor for signs and symptoms of TTP/HUS. Discontinue if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The safety of reinitiating KYPROLIS is not known.
Posterior Reversible Encephalopathy Syndrome (PRES)

Cases of PRES have occurred in patients receiving KYPROLIS. If PRES is suspected, discontinue and evaluate with appropriate imaging. The safety of reinitiating KYPROLIS is not known.
Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-ineligible Patients

In a clinical trial of transplant-ineligible patients with newly diagnosed multiple myeloma comparing KYPROLIS, melphalan, and prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher incidence of serious and fatal adverse events was observed in patients in the KMP arm. KMP is not indicated for transplant-ineligible patients with newly diagnosed multiple myeloma.
Embryo-fetal Toxicity

KYPROLIS can cause fetal harm when administered to a pregnant woman.
Females of reproductive potential should be advised to avoid becoming pregnant while being treated with KYPROLIS and for 6 months following the final dose. Males of reproductive potential should be advised to avoid fathering a child while being treated with KYPROLIS and for 3 months following the final dose. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.
ADVERSE REACTIONS

The most common adverse reactions in the combination therapy trials: anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper respiratory tract infection, hypokalemia.
The most common adverse reactions in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.
Please see full Prescribing Information at www.kyprolis.com.

About Amgen Oncology
Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient’s life – not just their cancer journey – so they can take control of their lives.

For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company’s history, moving with great speed to advance those innovations for the patients who need them.

At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do.

On December 10, 2019 Bristol-Myers Squibb Company (NYSE: BMY) reported clinical results from the QUAZAR AML-001 study, evaluating investigational agent CC-486 as maintenance therapy in a broad population of patients with front-line, newly diagnosed acute myeloid leukemia (AML) who have achieved remission with intensive induction chemotherapy (Press release, Bristol-Myers Squibb, DEC 10, 2019, View Source [SID1234552187]). Data were presented during a late-breaker oral presentation at the 2019 ASH (Free ASH Whitepaper) Annual Meeting in Orlando, Fla. In the QUAZAR AML-001 study, treatment with CC-486 in the maintenance setting provided patients a statistically significant and clinically meaningful improvement in overall survival (OS) and relapse-free survival (RFS), as compared to those patients treated with placebo.

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!

Patients in the phase 3, international, randomized, double-blind, placebo-controlled study QUAZAR AML-001 were at least 55 years old, had de novo or secondary AML with intermediate or poor-risk cytogenetics and had achieved their first complete remission (CR) or complete remission with incomplete count recovery (CRi) after intensive induction chemotherapy. Patients had received intensive induction chemotherapy, with or without consolidation chemotherapy per investigator’s choice and were deemed not candidates for hematopoietic stem-cell transplant prior to study entry.

"Despite a number of recent advances in the treatment of AML, the prognosis remains poor, as most patients will relapse and ultimately die of their disease," said Dr. Andrew Wei, MBBS, Ph.D., from Alfred Hospital and Monash University, Melbourne, Australia. "The role of maintenance therapy in AML has historically been a contentious issue. Based on the results of the QUAZAR study, we are excited about the clinical development of CC-486 and the potential to establish maintenance therapy as a new treatment paradigm for patients with AML in first remission."

Following intensive induction chemotherapy, 81% of patients had achieved a CR and 19% of patients had achieved a CRi. Eighty percent of patients had received at least one cycle of consolidation therapy prior to enrollment in the study. Four hundred seventy-two patients were then randomized 1:1 to receive initially either investigational CC-486 300mg (n=238) or placebo (n=234) once daily for 14 days of each 28-day cycle. Patients remained on treatment until unacceptable toxicity or disease progression.

At a median follow-up of 41.2 months, the primary endpoint of OS was significantly improved for patients receiving CC-486 compared to placebo. Median OS from time of randomization was 24.7 months in the CC-486 arm compared to 14.8 months for placebo (p=0.0009; HR 0.69 [95% CI: 0.55, 0.86]). Median RFS, the key secondary endpoint, was 10.2 months for those receiving CC-486 compared to 4.8 months for those receiving placebo (p=0.0001; HR 0.65 [95% CI: 0.52, 0.81]). Improvements in OS and RFS for those treated with CC-486 compared to placebo were demonstrated, regardless of cytogenetic risk category, prior consolidation or CR/CRi status at enrollment. Health-related quality of life (HRQoL) was preserved from baseline for patients receiving CC-486 compared to placebo during treatment.

The median duration of treatment was 12 cycles (1-80) for CC-486 and 6 cycles with placebo (1-73). The most commonly occurring adverse events (AEs) of all grades with CC-486 and placebo, respectively, were nausea (65% vs. 24%), vomiting (60% vs. 10%) and diarrhea (50% vs. 22%). The most common grade 3-4 AEs for CC-486 and placebo, respectively, were neutropenia (41% vs. 24%), thrombocytopenia (23% vs. 22%) and anemia (14% vs. 13%). Serious AEs were reported in 34% of CC-486 patients and 25% of placebo patients, and were mainly infections, which occurred in 17% and 8% of CC-486 and placebo patients, respectively. There were 13% of CC-486 patients and 4% of placebo patients who discontinued treatment due to AEs.

"We are extremely encouraged by the results of the QUAZAR AML-001 study as a part of our continuing commitment to both epigenetic research and myeloid diseases," said Samit Hirawat, M.D., Chief Medical Officer of Bristol-Myers Squibb. "We now look forward to taking the next steps to bring CC-486 to eligible AML patients in need."

Based on the results of QUAZAR AML-001, Bristol-Myers Squibb is planning regulatory submissions in the first half of 2020.

CC-486 is not approved for any use in any country.

About AML

Acute myeloid leukemia (AML) is the most common type of acute leukemia. AML starts in the bone marrow but moves quickly into the blood. Unlike in normal blood cell development, in AML the rapid build up of abnormal white blood cells in the bone marrow may interfere with the production of normal blood cells, resulting in decreased healthy white blood cells, red blood cells and platelets. AML is a complex, diverse disease associated with multiple genetic mutations and usually gets worse quickly if not treated. There will be an estimated 21,450 new cases of AML in the United States this year, accounting for 1.2% of all cancer cases, with an estimated 10,920 deaths resulting from the disease. There are an estimated 61,048 people living with AML in the United States.

About QUAZAR AML-001

QUAZAR AML-001 is a phase 3, international, randomized, double-blind, placebo-controlled study of CC-486 as AML maintenance therapy in patients who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy (with or without consolidation). The primary endpoint of the study was overall survival. Secondary endpoints included relapse-free survival (RFS), safety and tolerability, healthcare resource utilization and patient-reported outcomes per the FACIT-Fatigue Scale and EQ-5D questionnaire. The study enrolled 472 patients, randomized 1:1 to receive initially either oral CC-486 300mg or placebo once daily for 14 days of a 28-day cycle plus best supportive care. Patients remained on treatment until unacceptable toxicity or disease progression.

About CC-486

CC-486 is an oral hypomethylating agent that incorporates into DNA and RNA allowing for sustained epigenetic regulation due to prolonged exposure. The main mechanism of action is thought to be hypomethylation of DNA, as well as direct cytotoxicity to abnormal hematopoietic cells in the bone marrow. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation.

Bristol-Myers Squibb: Advancing Cancer Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase quality, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational chimeric antigen receptor (CAR) T-cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

On December 10, 2019 ImmunOs Therapeutics AG, a Swiss bio-technology company and leading developer of a next generation innate immunity focused immunotherapy platform for cancer, reported the closing of a Series A financing of CHF 15 million (Press release, ImmunOs Therapeutics, DEC 10, 2019, View Source [SID1234552203]). The round was co-led by the Basel life sciences venture capital firm BioMedPartners and Pfizer Ventures, the venture capital arm of Pfizer Inc. (NYSE: PFE), with the participation of Redalpine, Schroder Adveq, Wille Finance AG, BERNINA BioInvest Ltd alongside new private and existing investors. The financing will be used to complete the first-in-human trials with the company’s lead agent, iosH2, a potential new cancer treatment for both solid and liquid tumors. The funding will also be used to broaden the company’s novel immunotherapy iosH platform by advancing additional preclinical programs focusing on both cancer and auto-immunity.

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!

"Recent advances in the understanding of the innate immune system’s role in cancer provide a unique opportunity for ImmunOs Therapeutics and our partners. We value the ongoing support of all the current investors and welcome all the Series A round participants, specifically Pfizer Ventures and BioMedPartners, both of whom have demonstrated a strong commitment to the oncology field," said Sean R. Smith, CEO of ImmunOs Therapeutics AG.

Dr. Osiris Marroquin Belaunzaran, CSO and co-founder, added: "It is with great pleasure to see that our early research based on HLA open conformer modulation of immune cells is advancing toward a clinical drug candidate for human studies. Targeting the innate immune system to modulate the tumor microenvironment has been a key strategy for ImmunOs, and together with foundational approaches targeting the adaptive immune system such as PD-1 antibodies, we aim to produce a strong therapeutic benefit in difficult-to-treat cancer indications."

In conjunction with the financing, ImmunOs Therapeutics has expanded its Board of Directors to include four new members: Dr. Markus Hosang of BioMedPartners; Dr. Michael Baran of Pfizer Inc.; Dr. Reinhard Ambros, former head Novartis Venture Fund; and Dr. Daniel Vasella, former Chairman and CEO Novartis.

Dr. Markus Hosang noted: "At BioMedPartners, we have over the last 15 years very successfully invested in and brought forward several innovative early-stage cancer companies. We got particularly attracted by ImmunOs and its novel approach that also adds to existing treatment modalities and thus has the potential to provide novel medicines to cancer patients who do not obtain a long-term benefit from current therapies."

Dr. Michael Baran added: "Advances in understanding the role of the innate immune system is opening up opportunities to expand the potential of cancer immunotherapy. Pfizer Ventures is enthusiastic to support this emerging area through our investment in ImmunOs."

On December 10, 2019 Caris Life Sciences, a leading innovator in molecular science focused on fulfilling the promise of precision medicine, reported that it will present results from a study evaluating the prevalence of phosphatidylinositol-3-kinase (PI3K)/AKT/PTEN pathway alterations and co-alterations in patients with different subtypes of breast cancer. The molecular profiles of nearly 5,000 patients were evaluated using the Caris Molecular Intelligence Next-Generation Sequencing (NGS) technology, which identified pathogenic or presumed pathogenic mutations on the PI3K pathway using a 592-gene DNA sequencing panel.

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!

Results showed a high prevalence of hotspot mutations in PIK3CA and that 8% of breast tumors carry uncommon activating PIK3CA mutations. Additional genes activating the pathway including AKT1, PI3R1, PIK3R2 and PTEN were investigated and showed mutation rates ranging from 0.1% to 3%. In addition, the study revealed a significant increase in PD-L1 expression in tumor cells and high tumor mutational burden (TMB) in PIK3CA-AKT1-PTEN mutated cohorts.

The full results will be featured in Poster Session 4 on Friday, December 13, from 7:00-9:00 a.m. CT at the 2019 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas (Presentation #P4-09-04). The poster is titled, "Prevalence of phosphatidylinositol-3-kinase (PI3K) pathway alterations and co-alteration of other markers in breast cancer."

"PI3K and AKT inhibitors have been shown to have significant activity against tumor progression and to overcome resistance in breast cancer, and the recent advancement of the drug class to the clinical use in breast cancer is truly exciting," said investigator Filipa Lynce, M.D., an oncologist with Georgetown Lombardi Comprehensive Cancer Center and MedStar Georgetown University Hospital, a member of the Precision Oncology Alliance. "These results demonstrate a high incidence of common and uncommon mutations that activate PI3K pathway in these patients, which is meaningful for patient selection for the very promising drug class. The knowledge gained from this study on molecular alterations that co-occur with PI3K pathway activation could ultimately help identify novel drug combinations that have the potential to elicit synergistic growth inhibition."

Of the 4,895 molecular profiles submitted to Caris Life Sciences, 72.7% had at least one alteration in the PIK3CA-AKT1-PTEN pathway. PIK3CA was the most frequent alteration in HER2 positive breast cancer, and TNBC was the subtype with the lowest frequency of PIK3CA mutations (18.0% vs. 37% in other subtypes). Notable co-alterations in the TNBC cohort include increased PD-L1 expression high TMB and increased RAS signaling.

The Precision Oncology Alliance (POA) includes 31 academic, hospital and community-based cancer institutions, including nine NCI-designated Comprehensive Cancer Centers collaborating to further the understanding of molecular profiling. To date, the POA has presented over 100 abstracts and publications.

"Our data at SABCS 2019 continue to reinforce the need for further research in precision medicine in metastatic breast cancer care," said W. Michael Korn, M.D., Chief Medical Officer at Caris Life Sciences. "As the use of precision medicine continues to evolve, our ongoing work in tumor biology and biomarkers will have broad implications in helping to guide treatment decisions for patients across a range of tumor types, including breast cancer."

On December 10, 2019 Solasia Pharma K.K. (TSE: 4597, Headquarters: Tokyo, Japan, President & CEO: Yoshihiro Arai, hereinafter "Solasia") reported that it has entered into an exclusive license agreement with Maruho Co., Ltd. (Headquarters: Osaka, Japan, President & CEO: Koichi Takagi, hereinafter "Maruho") for commercialization of Solasia’s product SP-04 (PledOx, hereinafter "product"), a therapeutic agent for chemotherapy induced peripheral neuropathy (currently undergoing Phase III clinical trials; active ingredient name: calmangafodipir) in Japan (Press release, Solasia, DEC 10, 2019, View Source [SID1234552204]).

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!

Under the license agreement, Maruho will commercialize the product exclusively in Japan after Solasia completes development of the product. Based on the license agreement, Solasia will supply the product exclusively to Maruho, and Maruho will pay Solasia an upfront payment of 1.0 billion yen and milestone payments based on progress in development and marketing up to a total of 18.0 billion yen.

In addition to the above license agreement, Solasia and Maruho have entered into a capital alliance agreement whereby Maruho acquires Solasia shares by a third-party allotment with a view to maintain a close business relationship going forward.

Capital alliance format:

Acquisition of newly issued Solasia shares by Maruho in third-party allotment

Pay-in date:

December 26, 2019

Number of shares issued:

11,324,000 Solasia common stock

Issue price per share:

151 yen (closing price on December 9, 2019)

Total issue amount:

1,709,924,000 yen

Shareholding ratio after issue:

Maruho will hold 9.70% of outstanding shares in Solasia

Lock-up agreement:

Maruho must obtain prior consent from Solasia if transferring its shareholding before the day following the date of the initial announcement of the clinical trial results and others by Solasia after completion of the two Phase III trials of the product currently under way.

Solasia’s top shareholder, ITOCHU Corporation must obtain prior consent from Solasia if transferring its shareholding within one year of the pay-in date stated above.

Use of proceeds:

For in-licensing and development of new pipeline product SP-05.

Maruho specializes in dermatology and has contributed to improving the quality of life (QOL) of patients suffering from skin disorders caused by cancer treatment. This time, in order to further contribute to cancer patients and their families, Maruho decided to obtain the rights to commercialize the product. Solasia specializes in oncology in Asia, and 3 of their 4 existing and development products include drugs that treat the side effects of anticancer drugs. Solasia is yet to establish an in-house sales force in Japan. Therefore, in light of the steady progress of the phase III clinical trial for the product, Solasia decided to derive the commercialization rights to Maruho who share the common philosophy of the importance of improving patient QOL.

Koichi Takagi, President and CEO of Maruho, commented as follows:
"Solasia is a specialty pharmaceutical company in oncology. The company supports patients undergoing cancer treatment and their families by developing not only anticancer drugs, but also cancer supportive care products to improve patient QOL. In collaboration with Solasia, we will continue to do our best to help cancer patients and their families further by combining Solasia’s extensive knowledge in oncology with the experience we have gained in improving patient QOL."

Yoshihiro Arai, President and CEO of Solasia, commented as follows:
"Maruho is a leading company in Japan in the dermatology area that has gained from many years’ experience with cancer and other patients the insight that improving patient QOL is as important as treating the underlying disease. We are confident that Maruho, with its wealth of knowledge and experience in patient QOL, is the best partner for Solasia, as we can broadly share the expectations and importance of our development product SP-04 in the treatment of chemotherapy-induced peripheral neuropathy and work together to improve patient QOL.".