On September 28, 2017 The U.S. Food and Drug Administration reported that they approved Verzenio (abemaciclib) to treat adult patients who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer that has progressed after taking therapy that alters a patient’s hormones (endocrine therapy). Verzenio is approved to be given in combination with an endocrine therapy, called fulvestrant, after the cancer had grown on endocrine therapy. It is also approved to be given on its own, if patients were previously treated with endocrine therapy and chemotherapy after the cancer had spread (metastasized) (Press release, US FDA, SEP 28, 2017, View Source [SID1234520694]).

“Verzenio provides a new targeted treatment option for certain patients with breast cancer who are not responding to treatment, and unlike other drugs in the class, it can be given as a stand-alone treatment to patients who were previously treated with endocrine therapy and chemotherapy,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

Verzenio works by blocking certain molecules (known as cyclin-dependent kinases 4 and 6), involved in promoting the growth of cancer cells. There are two other drugs in this class that are approved for certain patients with breast cancer, palbociclib approved in February 2015 and ribociclib approved in March 2017.

Breast cancer is the most common form of cancer in the United States. The National Cancer Institute at the National Institutes of Health estimates approximately 252,710 women will be diagnosed with breast cancer this year, and 40,610 will die of the disease. Approximately 72 percent of patients with breast cancer have tumors that are HR-positive and HER2-negative.

The safety and efficacy of Verzenio in combination with fulvestrant were studied in a randomized trial of 669 patients with HR-positive, HER2-negative breast cancer that had progressed after treatment with endocrine therapy and who had not received chemotherapy once the cancer had metastasized. The study measured the length of time tumors did not grow after treatment (progression-free survival). The median progression-free survival for patients taking Verzenio with fulvestrant was 16.4 months compared to 9.3 months for patients taking a placebo with fulvestrant.

The safety and efficacy of Verzenio as a stand-alone treatment were studied in a single-arm trial of 132 patients with HR-positive, HER2-negative breast cancer that had progressed after treatment with endocrine therapy and chemotherapy after the cancer metastasized. The study measured the percent of patients whose tumors completely or partially shrank after treatment (objective response rate). In the study, 19.7 percent of patients taking Verzenio experienced complete or partial shrinkage of their tumors for a median 8.6 months.

Common side effects of Verzenio include diarrhea, low levels of certain white blood cells (neutropenia and leukopenia), nausea, abdominal pain, infections, fatigue, low levels of red blood cells (anemia), decreased appetite, vomiting and headache.

Serious side effects of Verzenio include diarrhea, neutropenia, elevated liver blood tests and blood clots (deep venous thrombosis/pulmonary embolism). Women who are pregnant should not take Verzenio because it may cause harm to a developing fetus.

The FDA granted this application Priority Review and Breakthrough Therapy designations.

The FDA granted the approval of Verzenio to Eli Lilly and Company.

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.

On September 29, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Perjeta (pertuzumab), in combination with Herceptin (trastuzumab) and chemotherapy (the Perjeta-based regimen), for adjuvant (after surgery) treatment of HER2-positive early breast cancer (eBC) (Press release, Hoffmann-La Roche, SEP 28, 2017, View Source [SID1234520698]). The FDA is expected to make a decision on approval by 28 January 2018. The sBLA is based on results of the phase III APHINITY study. A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.

“We are pleased to receive Priority Review for the Perjeta-based regimen for the adjuvant treatment of HER2-positive early breast cancer,” said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. “The goal of treating breast cancer early is to provide people with the best chance for a cure. Despite advances in the treatment of this disease, many people treated with the current standard of care still see their cancer return.”

The combination of Perjeta, Herceptin and chemotherapy is licensed as a neoadjuvant (before surgery) treatment for people with HER2-positive eBC in more than 85 countries worldwide following approvals by the European Medicines Agency (EMA) and the US FDA. In the US, the regimen is currently available under the FDA Accelerated Approval Program. This sBLA seeks to convert the current accelerated approval to full approval in the US. Additionally, the APHINITY trial reflects the commitment to evaluate the Perjeta-based regimen as part of a complete treatment approach for eBC. Perjeta in combination with Herceptin and docetaxel chemotherapy is also approved in the US and the European Union for people with previously untreated HER2-positive metastatic breast cancer.

About APHINITY1
APHINITY (Adjuvant Pertuzumab and Herceptin IN Initial TherapY in Breast Cancer, NCT01358877/ BO25126/ BIG 4-11) is an international, phase III, randomised, double-blind, placebo-controlled, two-arm study evaluating the efficacy and safety of Perjeta plus Herceptin and chemotherapy compared to Herceptin and chemotherapy as adjuvant therapy in 4,805 people with operable HER2-positive eBC. The primary efficacy endpoint of the APHINITY study is invasive disease-free survival (iDFS), which in this study is defined as the time a patient lives without return of invasive breast cancer at any site or death from any cause after adjuvant treatment. Secondary endpoints include cardiac and overall safety, overall survival, disease-free survival and health-related quality of life.

On September 28, 2017 CBT Pharmaceuticals (CBT), a biopharmaceutical company focused on developing innovative oncology therapeutics harnessing the immune system and targeting specific molecular pathways to tame cancer, reported that the first subject has been dosed in the Phase 1 multi-center study, CBT-101-01 (Press release, CBT Pharmaceuticals, SEP 28, 2017, View Source [SID1234520681]). CBT-101 is a specific oral inhibitor of the c-Met kinase. This is the company’s first clinical trial in the United States (NCT03175224). Following identification of a dose for CBT-101, the trial is planned to expand into tumor specific cohorts.

“This is an important milestone for CBT and its employees. We are also extremely grateful to the patients and clinical researchers at premier U.S. institutions that will contribute to the evaluation of CBT-101,” said Sanjeev Redkar, Ph.D., President and Chief Executive Officer. “CBT-101 has demonstrated strong inhibition of tumor growth in cell lines and patient derived models across multiple tumor types with c-Met fusions, mutations or amplifications. We anticipate the clinical results so that we can explore single agent development as well as combination approaches.”

“The aberrant activation of c-Met has been demonstrated to be highly correlated with outcome in many cancer indications, including kidney, lung, gastric, esophageal and brain cancer and plays a major role in cancer pathogenesis including tumor growth, angiogenesis and metastasis, as well as the suppression of cell death,” said Anthony El-Khoueiry, M.D., Associate Professor of Clinical Medicine and Phase 1 Program Director at USC Norris Comprehensive Cancer Center. “Through our research collaboration with CBT Pharmaceuticals and the cadre of investigators on this trial, we look forward to characterizing CBT-101 safety profile and dose, and defining a path for further development.”

CBT-101-01 Clinical Trial

This is a Phase 1, multi-center, open-label, 2-part Dose Escalation Segment with a Dose and Disease Expansion Cohort study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of CBT-101 monotherapy in subjects with advanced solid tumors with c-Met dysregulation. These findings will be used to establish a recommended Phase 2 dose for future clinical trials. A total of approximately 68 subjects will be enrolled.

There are two other Phase 1 trials with CBT-101 (PLB1001) ongoing in China – one in Met-positive Advanced Non-Small Cell Lung Cancer and the other in PTPRZ1-MET Fusion Gene Positive Recurrent High-Grade Gliomas.

More information on all trials is available at ClinicalTrials.gov.

CBT-101 Oral Capsule (PLB1001)

CBT-101 is a novel small molecule drug that targets the epithelial to mesenchymal transition (EMT) pathway that is dysregulated in several tumors. It is a specific inhibitor of the c-Met receptor. CBT-101 has demonstrated tumor inhibitory effect in a variety of human primary c-Met amplified gastric, hepatic, pancreatic and lung cancer xenograft animal models with c-Met fusions, mutations or amplifications (AACR, 2017).

On September 28, 2017 ERYTECH Pharma (Paris:ERYP) (ADR:EYRYY), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported the determination of the recommended pivotal Phase 3 dosing from its U.S. Phase 1 dose escalation study with eryaspase (GRASPA) in first line treatment of adult ALL patients (Press release, ERYtech Pharma, SEP 28, 2017, View Source [SID1234520680]).

The U.S. Phase 1 study with eryaspase (GRASPA) is an open label dose escalation study evaluating the safety of eryaspase in combination with CALGB 8811 protocol for first line treatment of adult ALL patients. The study is performed at five clinical sites across the United States. Prof. Dr. Richard Larson, director of the Hematologic Malignancies Clinical Research Program at the University of Chicago, is the principal investigator of the study.

ERYTECH recently announced that all patients had been treated in the third dose escalation cohort of this Phase 1 study. The steering committee of the study reviewed the safety data of all three treatment cohorts and agreed to pursue further development at the dose level of 100 U/kg. This dose level had been previously recommended following ERYTECH’s Phase 2 study in elderly ALL patients. It is also the dose level used in the Phase 2b study in second line, metastatic pancreatic cancer, that recently reported positive efficacy and safety results, and in the ongoing Phase 2b study in AML, from which top-line results are expected by the end of this year.

In parallel with running an expansion cohort of this Phase 1 study at this recommended dose, ERYTECH will potentially initiate the steps toward the launch of a pivotal Phase 3 study in first line adult ALL patients at this dose level.

On September 28, 2017 bluebird bio, Inc. (Nasdaq: BLUE), a clinical-stage company committed to developing potentially transformative gene therapies for serious genetic diseases and T cell-based immunotherapies for cancer, reported the treatment of the first patient with relapsed/refractory multiple myeloma in a Phase 1 study of bb21217 (Press release, bluebird bio, SEP 28, 2017, View Source [SID1234520679]). bb21217 is an investigational chimeric antigen receptor T cell (CAR T) therapy targeting B cell maturation antigen (BCMA). bluebird bio is developing bb21217 in collaboration with Celgene Corporation. bluebird bio also announced today that Celgene has exercised its option to exclusively license bb21217, under the terms of the collaboration between the two companies.

“bb21217, bluebird’s second oncology program to enter the clinic, complements bb2121, which has demonstrated encouraging safety and efficacy results in an ongoing Phase 1 trial. With bb21217, we manufacture a CAR T cell product enriched for ‘memory T cells’ – a long-lived, more potent T cell subtype – which in preclinical in vivo studies has shown improved anti-tumor activity,” said Philip Gregory, chief scientific officer, bluebird bio. “While the clinical data we have shared to date from our bb2121 program have shown deep and durable responses, we know that multiple myeloma is an aggressive and historically incurable cancer. With our partners at Celgene, we are excited to bring forward a second program reflecting our commitment to exploring all avenues to deliver cutting edge therapies to patients.”

“The advancement of bb21217 into the clinic builds upon the success of our first-generation program and is one more testament to bluebird’s and Celgene’s combined leadership in the field of anti-BCMA CAR T therapies,” said Rupert Vessey, EVP and President, Global Research & Early Development, Celgene. “We look forward to our continued partnership with bluebird to unleash the full potential of anti-BCMA CAR T therapies for patients living with historically incurable cancers.”

The bluebird bio and Celgene collaboration focuses on developing product candidates targeting BCMA for the treatment of patients with multiple myeloma. By exercising its exclusive option under the terms of the collaboration, Celgene will be responsible for worldwide development and commercialization of bb21217 after Phase 1. bluebird bio is responsible for the development of bb21217 through the completion of the CRB-402 Phase 1 study and has an option to share in the development, promotion and profits in the United States. bluebird bio will receive a $15 million option exercise payment from Celgene, and bluebird bio is also eligible to receive specified development, regulatory and commercial milestone payments and royalty payments on net sales.

About the CRB-402 Study
The primary objective of the CRB-402 study is to evaluate the maximum tolerated dose of bb21217 and determine the recommended Phase 2 dose. The secondary objective is preliminary efficacy data, measured using the International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma. The first portion of the study includes a dose-escalation phase in which cohorts of patients will receive ascending doses of bb21217 to determine the maximum tolerated dose and establish a recommended Phase 2 dose. The second portion of the study is a dose expansion phase where patients will receive bb21217 to further evaluate the safety, tolerability and clinical activity at the recommended Phase 2 dose.