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Puma Announces Availability of NERLYNX™ (neratinib) for Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer in the United States

On July 31, 2017 Puma Biotechnology, Inc. (Nasdaq: PBYI) reported that NERLYNX (neratinib) tablets, formerly known as PB272, is now commercially available by prescription in the United States (Press release, Puma Biotechnology, JUL 31, 2017, View Source [SID1234519956]). The U.S. Food and Drug Administration (FDA) approved NERLYNX on July 17, 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy.

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FDA approval was based on the Phase III ExteNET trial, a multicenter, randomized, double-blind, placebo-controlled trial of NERLYNX following adjuvant trastuzumab treatment. Women (n=2,840) with early stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomized to receive either NERLYNX (n=1,420) or placebo (n=1,420) for one year.

The results of the ExteNET trial demonstrated that after two years of follow-up, invasive disease-free survival (iDFS) was 94.2% in patients treated with NERLYNX compared with 91.9% in those receiving placebo (HR 0.66; 95% CI: 0.49, 0.90, p=0.008).

The most common adverse reactions (≥5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, epistaxis, weight loss, and urinary tract infection. The most common adverse reaction leading to discontinuation was diarrhea, which was observed in 16.8% of NERLYNX-treated patients. Increases in liver transaminases led to drug discontinuation in 1.7% of NERLYNX-treated patients.

"Like many women with breast cancer, those with HER2-positive disease often struggle with anxiety and fear of recurrence," said Jennifer Merschdorf, Chief Executive Officer of Young Survival Coalition. "We are always eager for treatment advances that may provide an opportunity to further reduce the risk of recurrence."

"Despite advances in the treatment of early stage HER2-positive breast cancer, there remains a need for further therapeutic improvements in order to attempt to further reduce the risk of disease recurrence," said Puma Biotechnology CEO and President Alan H. Auerbach. "We are pleased to be able to bring this new medicine to patients with breast cancer. We would like to express our appreciation to the patients, caregivers and physicians who contributed to the NERLYNX clinical development program and, more specifically, the ExteNET trial."

To help ensure patients have access to NERLYNX, Puma has implemented the Puma Patient Lynx support program to assist patients and healthcare providers with reimbursement support and referrals to resources that can help with financial assistance. More information on the Puma Patient Lynx program can be found at www.NERLYNX.com or 1-855-816-5421.

The full prescribing information for NERLYNX is available at www.NERLYNX.com. The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first dose of NERLYNX and continued during the first 2 months (56 days) of treatment and as needed thereafter.

A Marketing Authorisation Application for neratinib is under review by the European Medicines Agency (EMA).

About HER2-Positive Breast Cancer

Approximately 20% to 25% of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

Indication

NERLYNX is a tyrosine kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

Important Safety Information

There are possible side effects of NERLYNX. Patients must contact their doctor right away if they experience any of these symptoms. NERLYNX treatment may be stopped or the dose may be lowered if the patient experiences any of these side effects.

Diarrhea

Diarrhea is a common side effect of NERLYNX. The diarrhea may be severe, and you may get dehydrated. Your healthcare provider should prescribe the medicine loperamide for you during your first 2 cycles (56 days) of NERLYNX and then as needed. To help prevent or reduce diarrhea:

You should start taking loperamide with your first dose of NERLYNX.
Keep taking loperamide during the first 2 cycles (56 days) of NERLYNX treatment and then as needed. Your healthcare provider will tell you exactly how much and how often to take loperamide.
While taking loperamide, you and your healthcare provider should try to keep the number of bowel movements that you have at 1 or 2 bowel movements each day.
Tell your healthcare provider if you have more than 2 bowel movements in 1 day, or if you have diarrhea that does not go away.
Contact your healthcare provider right away if you have severe diarrhea or if you have diarrhea along with weakness, dizziness, or fever.

Liver Problems

Changes in liver function tests are common with NERLYNX. The patient’s doctor will do tests before starting treatment, monthly during the first 3 months, and then every 3 months as needed during treatment with NERLYNX. NERLYNX treatment may be stopped or the dose may be lowered if your liver tests show severe problems. Symptoms of liver problems may include tiredness, nausea, vomiting, pain in the right upper stomach area (abdomen), fever, rash, itching, yellowing of your skin or whites of your eyes.

Pregnancy

Patients should tell their doctor if they are planning to become pregnant, are pregnant, plan to breastfeed, or are breastfeeding. NERLYNX can harm your unborn baby. Birth control should be used while a patient is receiving NERLYNX and for at least 1 month after the last dose. If patients are exposed to NERLYNX during pregnancy, they must contact their healthcare provider right away.

Common side effects in patients treated with NERLYNX

In clinical studies, the most common side effects seen in patients taking NERLYNX were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis (dry or inflamed mouth, or mouth sores), decreased appetite, muscle spasms, dyspepsia, changes in liver blood tests results, nail problems, dry skin, abdominal distention, weight loss, and urinary tract infection.

Patients should tell their doctor right away if they are experiencing any side effects. Report side effects to the FDA at 1-800-FDA-1088 or View Source . Patients and caregivers may also report side effects to Puma Biotechnology at 1-844-NERLYNX (1-844-637-5969).

Please see Full Prescribing Information, available at www.NERLYNX.com .

Geron Announces Updates to Imetelstat Clinical Development

On July 31, 2017 Geron Corporation (Nasdaq:GERN) reported updates to the clinical development plans for IMerge and IMbark, the ongoing trials of the telomerase inhibitor imetelstat in lower risk myelodysplastic syndromes (MDS) and relapsed or refractory myelofibrosis (MF), respectively, being conducted by Janssen Research & Development, LLC (Press release, Geron, JUL 31, 2017, View Source [SID1234519955]). For IMerge, Part 1 will be expanded to enroll additional patients in a refined MDS population to confirm the clinical benefit and safety observed from current results. For IMbark, the trial remains unchanged. Geron expects that the IMbark protocol-specified primary analysis, the completion of which triggers a future Continuation Decision by Janssen, will begin no later than the third quarter of 2018.

Original Trial Design

IMerge (NCT02598661) is a Phase 2/3 clinical trial evaluating imetelstat in transfusion dependent patients with Low or Intermediate-1 risk MDS who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The clinical trial is in two parts: Part 1 is a Phase 2, open-label, single-arm design in approximately 30 patients and Part 2 is designed to be a Phase 3, randomized, controlled trial in approximately 170 patients. The primary efficacy endpoint is the rate of red blood cell (RBC) transfusion independence (TI) lasting at least 8 weeks.

Trial Status Update

In Part 1 of IMerge, 32 patients were enrolled, of which a subset of 13 patients had not received prior treatment with either a hypomethylating agent (HMA) or lenalidomide and did not have a del(5q) chromosomal abnormality. As of May 2017, the 13-patient subset showed an increased durability and rate of transfusion independence compared to the overall trial population (≥8-week RBC-TI: 53.8% vs 34.4%). The safety profile in Part 1 was consistent with prior clinical trials of imetelstat in hematologic malignancies, and no new safety signals were identified. The most common adverse events were cytopenias, which were manageable, and included grade 3/4 neutropenia and thrombocytopenia.

Based on these data from the 13-patient subset, the Joint Steering Committee has decided to amend Part 1 of the protocol to enroll approximately 20 additional patients who are non-del5q and naïve to HMA and lenalidomide treatment in order to increase the experience and confirm the benefit-risk profile of imetelstat dosed at 7.5 mg/kg every four weeks in this refined target patient population. Enrollment into the expanded Part 1 is expected to begin in the fourth quarter of 2017.

Separately, a data package and proposed refinements to the trial design for Part 2 of IMerge were previously provided to the FDA following an internal data review completed by Janssen in April, and related interactions are ongoing. Feedback from ongoing FDA interactions, data from the expanded Part 1, and other imetelstat program information, including the protocol-specified primary analysis for IMbark, are expected to inform Janssen’s decision of whether to move forward to Part 2 of IMerge.

Detailed results for the original 32 patients in Part 1 of IMerge, including key secondary endpoints of hematologic improvement and rate of RBC-TI lasting at least 24 weeks, as well as duration of response and detailed safety information, will be submitted for presentation at a major medical conference.

IMbark

Trial Status Update

IMbark (NCT02426086) is a Phase 2 trial in patients with Intermediate-2 or High Risk MF who have relapsed after or are refractory to prior treatment with a JAK inhibitor. The trial continues without modification, and patients remaining in the treatment phase may continue to receive imetelstat. All safety and efficacy assessments will be conducted as planned in the protocol, which includes an assessment of a potential survival benefit associated with imetelstat treatment. To date, median overall survival has not yet been reached in either the 4.7 mg/kg or 9.4 mg/kg dosing arm. Enrollment of new patients to the trial remains suspended because the total number of patients enrolled to date is adequate to perform the protocol-specified primary analysis. Geron expects Janssen to perform an internal data review in the first quarter of 2018 to enable a potential protocol amendment to allow the long-term treatment and follow-up of patients, including for survival, beyond the current April 2018 per-protocol end-of-study date.

Continuation Decision

The Joint Steering Committee has agreed that the timing of the protocol-specified primary analysis for IMbark will begin upon the earlier of either a pre-specified number of deaths occurring in the trial or the end of the third quarter of 2018. Following completion of this primary analysis, which includes an assessment of potential survival benefit associated with imetelstat treatment, Janssen will notify Geron whether it elects to maintain the license rights and continue the development of imetelstat in any indication, i.e., the Continuation Decision.

About Imetelstat

Imetelstat (GRN163L; JNJ-63935937) is a potent and specific inhibitor of telomerase that is administered by intravenous infusion. This first-in-class compound, discovered by Geron, is a specially designed and modified short oligonucleotide, which targets and binds directly with high affinity to the active site of telomerase. Preliminary clinical data suggest imetelstat has disease-modifying activity by inhibiting the progenitor cells of the malignant clones associated with hematologic malignancies in a relatively select manner. Most commonly reported adverse events in imetelstat clinical studies include fatigue, gastrointestinal symptoms and cytopenias. Imetelstat has not been approved for marketing by any regulatory authority.

Transgene: First Patient Dosed in a Phase 1/2 Trial of Pexa-Vec + Opdivo® for the First-Line Treatment of Advanced Liver Cancer

On July 31, 2017 Transgene (Euronext Paris: TNG), a company that designs and develops viral-based immunotherapies, reported that the first patient has been treated in a Phase 1/2 clinical trial evaluating the combination of Pexa-Vec with Opdivo (nivolumab) as a first-line treatment of advanced hepatocellular carcinoma (HCC), which accounts for approximately 75% of liver cancers (Press release, Transgene, JUL 31, 2017, View Source [SID1234519950]).

This open-label trial will assess the safety and tolerability as well as the anti-tumor activity and efficacy of this immunotherapy combination regimen in up to 36 patients (NCT03071094). The principal investigator of this multi-center trial is Prof Olivier Rosmorduc, MD, Head of Hepatogastroenterology department at La Pitié-Salpêtrière Hospital in Paris (France). More information on the trial is available on clinicaltrials.gov. Pexa-Vec: an oncolytic immunotherapy that has shown efficacy Pexa-Vec is an oncolytic immunotherapy product based on an oncolytic vaccinia virus expressing GMCSF. In a Phase 2 trial of Pexa-Vec in first-line HCC, overall survival was improved in a dose dependent manner. The median overall survival was 14.1 months for the high-dose group compared to 6.7 months for the low-dose group. Pexa-Vec is designed to: – selectively destroy cancer cells through the direct lysis (breakdown) of cancer cells via viral replication, – reduce the blood supply to tumors through tumor vascular disruption, and – stimulate the body’s immune response against cancer cells. Pexa-Vec + Opdivo (nivolumab): a promising immunotherapy combination regimen Pexa-Vec’s mechanism of action and its safety profile make it an appropriate candidate for use in combination with immune checkpoint inhibitors (ICIs) such as nivolumab. Nivolumab (Opdivo, Bristol-Myers Squibb) is a monoclonal antibody targeted against the PD-1 receptor. It is approved in several cancer indications and is currently being investigated in HCC within a global Phase 3 trial. By targeting two distinct steps in the immune response against cancer cells, the combination of Pexa-Vec and nivolumab has the potential to be significantly more effective than either product alone. There is a strong scientific rationale that suggests that Pexa-Vec’s anti-cancer effects could be enhanced by combining it with nivolumab, which suppresses the cancer cells’ ability to escape the body’s immune response. Commenting on this innovative clinical trial, Prof Olivier Rosmorduc, MD, head of Hepatogastroenterology department at La Pitié-Salpêtrière Hospital in Paris and principal investigator of the trial, added: "Improving the treatment of HCC needs a therapeutic approach capable of significantly boosting the immune system. I am confident that combining immunotherapies with local and systemic effects such as anti-PD1 nivolumab and the oncolytic virus Pexa-Vec is a powerful strategy to better treat patients with advanced hepatocellular carcinoma."
Page 2 / 2 Maud Brandely, Chief Medical Officer of Transgene, said: "HCC has a dismal prognosis which has been marginally improved by current therapeutic options. Preclinical and clinical data generated respectively with Pexa-Vec and nivolumab suggest that, in combination, these novel immunotherapies, with their complimentary modes of action, have the potential to be more active than each single agent alone. This may translate into better response rate and increased overall survival in HCC patients."

NantKwest Announces Durable Complete Responses in Phase I Trial of aNK Cell Therapy in Patients with Relapsed Hematological Malignancies

On July 31, 2017 NantKwest Inc. (Nasdaq:NK), a pioneering, next-generation, clinical-stage immunotherapy company focused on harnessing the unique power of the immune system using natural killer (NK) cells to treat cancer, infectious diseases, and inflammatory diseases, reported the final results of a phase I clinical trial of the company’s aNK cell therapy platform in relapsed hematological malignancies (Press release, NantKwest, JUL 31, 2017, http://ir.nantkwest.com/phoenix.zhtml?c=254059&p=RssLanding&cat=news&id=2290212 [SID1234519949]).

The data published in the journal Oncotarget by investigators at Princess Margaret Cancer Centre in Toronto, Canada, demonstrated continuing evidence of safety and efficacy, with an overall response rate of 42% and no evidence of grade 3 or 4 adverse events from the infusions. Of note 2 out of the 12 patients in the safety study with relapsed Hodgkin’s Lymphoma and Multiple Myeloma, demonstrated durable complete response with single agent aNK therapy, and remain free of disease to date, 10 years and 2 years respectively.

"Our study was designed to assess safety and preliminary evidence of efficacy in patients with relapsed, refractory hematological malignancies whose disease recurred after autologous hematopoietic cell transplantation (AHCT). In this heavily pretreated patient population that has a particularly poor prognosis, we demonstrated safety with minimal toxicity and showed preliminary evidence of efficacy, taking advantage of the unique properties of natural killer (NK) cells as an immunotherapeutic agent," said Armand Keating, MD, FRCP(C), Director, Cell Therapy Program, Princess Margaret Cancer Centre and University Health Network.

Dr. Keating continued, "In this clinical study completed in 2015 of 12 patients with lymphoma and multiple myeloma who had relapsed after AHCT for refractory/relapsed disease, we report encouraging results with four patients (33%) currently alive and two complete responses, one for over two years and the second for over 10 years and conclude that aNK cell therapy warrants further clinical investigation."

Patrick Soon-Shiong, Chairman and CEO of NantKwest commented, "Consistent with previous studies, Dr. Keating’s clinical trial results, reporting a 42% overall response rate, provide additional clinical validation of the unique potential to deliver long-term remissions with limited toxicity using the company’s novel NK cell therapy. Our aNK cell therapy is currently in an ongoing Phase II clinical study in Merkel cell carcinoma and represent a critical, foundational component in the company’s recently launched NANT Cancer Vaccine clinical trial program."

Dr. Soon-Shiong continued, "We believe our product portfolio of novel off-the-shelf NK cell therapies is unique in offering a more uniform, consistent and optimized product potency with minimal toxicity and we remain focused on translating these unique advantages to patient care as rapidly as possible."

aNK Cell Therapy Platform

NantKwest’s aNK cell therapy platform is being developed as an allogeneic, off-the-shelf therapy, offering a potent, standardized, uniform and consistent product, further optimized to enhance the key capability of natural killer cells to directly target and kill cancer cells. This novel cell therapy is currently in an ongoing Phase II clinical trial in Merkel cell carcinoma and is a critical, foundational component in the company’s recently launch NANT Cancer Vaccine clinical trial program.

About NANT Cancer Vaccine

The NANT Cancer Vaccine is the first combination immunotherapy protocol to orchestrate the delivery of metronomic low dose radiation and chemotherapy with molecularly informed tumor associated antigen vaccines and natural killer cells, to activate the innate and adaptive immune system and to induce immunogenic cell death. By inducing immunogenic cell death and protecting as well as enhancing the innate and adaptive immune system, the NANT Cancer Vaccine seeks to attain long-term sustainable remission of multiple tumor types with lower toxicity and higher efficacy than current standards of care.

Amgen And Allergan Submit Biosimilar Biologics License Application For ABP 980 To US Food And Drug Administration

On July 31, 2017 Amgen (NASDAQ:AMGN) and Allergan plc. (NYSE:AGN) reported the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for ABP 980, a biosimilar candidate to Herceptin (trastuzumab) (Press release, Amgen, JUL 31, 2017, View Source [SID1234519947]). Amgen and Allergan are collaborating on four oncology biosimilar medicines, including ABP 980 which is the second to be submitted for FDA approval.

"The submission of ABP 980 for FDA review is an exciting milestone and speaks to our joint commitment with Allergan to deliver quality oncology biosimilars to patients," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Approval of ABP 980 would provide more patients access to a high-quality therapy with a proven safety and efficacy profile. We look forward to further discussions with the FDA."

"Today’s submission is our second U.S. biosimilar submission in less than a year as part of our collaboration with Amgen," said David Nicholson, chief R&D officer at Allergan. "We’re proud of the progress we’ve made so far and look forward to continuing our work to bring more biosimilars to market."

ABP 980 is a biosimilar candidate to trastuzumab, a recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody that targets HER2. Trastuzumab is approved for the treatment of HER2-positive adjuvant breast cancer, metastatic breast cancer and metastatic gastric cancer in the U.S.

The BLA submission includes analytical, pharmacokinetic and clinical data, as well as pharmacology and toxicology data. The Phase 3 comparative efficacy, safety and immunogenicity study was conducted in adult female patients with HER2-positive early breast cancer.

Amgen and Allergan are collaborating on the development and commercialization of four oncology biosimilars. Amgen has a total of 10 biosimilars in its portfolio, one of which has been approved by the FDA.

About ABP 980
ABP 980 is being developed as a biosimilar to trastuzumab, a recombinant DNA-derived humanized monoclonal immunoglobulin G1 kappa antibody approved in many regions for the treatment of HER2-overexpressing early breast cancer, adjuvant breast cancer, metastatic breast cancer and metastatic gastric cancer. The active ingredient of ABP 980 is a humanized monoclonal antibody that has the same amino acid sequence as trastuzumab. ABP 980 has the same pharmaceutical dosage form and strength as trastuzumab. Amgen and Allergan also submitted a Marketing Authorization Application to the European Medicines Agency for ABP 980 earlier this year.