1stOncology™: Cancer Intelligence Service – Page 16174 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Phase II Copanlisib Data Show Durable Tumor Response in Indolent Non-Hodgkin’s Lymphoma

On March 31, 2017 Bayer reported positive data on its investigational compound copanlisib, an intravenous pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor with predominant inhibitory activity against PI3K-α and PI3K-δ isoforms (Press release, Bayer, MAR 31, 2017, View Source;dcp=Phase-II-Copanlisib-Data-Show-Durable-Tumor-Response-in-Indolent-Non-Hodgkins-Lymphoma&ccm= [SID1234518413]). The Phase II CHRONOS-1 trial, an open-label, single-arm study of copanlisib evaluating patients with relapsed or refractory indolent non-Hodgkin’s lymphoma (iNHL), met its primary endpoint of a pre-specified objective response rate (ORR). The results across all patient groups show an ORR of 59.2%, with a 12% complete response (CR) rate and a median duration of response (DOR) of more than 98 weeks (687 days). These data will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2017 Annual Meeting in Washington, D.C., USA in the Novel Agent and Intervention Clinical Trials session on April 4, 2017 from 3:05 PM – 3:20 PM (ET).

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!

"Based on the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) guidelines, inhibition of the PI3K pathway has been shown to be an effective therapeutic strategy in treating indolent lymphomas, like follicular lymphoma; however, concerns exist about the safety of available oral PI3K inhibitors, highlighting the need for new approaches," said Martin Dreyling, Professor of Medicine at the University of Munich Hospital in Grosshadern. "The results of CHRONOS-1 demonstrate that intermittent intravenous administration of copanlisib achieved durable efficacy with a manageable safety profile in this difficult-to-treat patient population."

The full analysis set comprised 142 patients, of which 141 patients had iNHL. At the time of analysis, median duration of treatment was 22 weeks and 46 patients remained on treatment. In the follicular lymphoma (FL) subset of CHRONOS-1 (n=104), copanlisib treatment resulted in an ORR of 58.7%, including a CR of 14.4% and a median DOR of more than 52 weeks (370 days). The safety and tolerability were consistent with previously published data on copanlisib. The most common treatment-related adverse events were transient hyperglycemia (all grades: 49%/Grade ≥3: 40%), which did not show severity above Grade 4 and hypertension (all grades: 29%/Grade ≥3: 23%), which did not show severity above Grade 3.

"NHL is the tenth most common cancer worldwide and one of the most common cancers in the U.S. Despite treatment advances, most indolent NHL patients relapse after, or are refractory to, current therapies," said Robert LaCaze, Executive Vice President and Head of the Oncology Strategic Business Unit at Bayer. "The positive results from CHRONOS-1 are an important milestone and reflect the potential clinical utility of copanlisib in addressing the unmet medical need in patients with malignant lymphoma."

Other copanlisib data to be presented at AACR (Free AACR Whitepaper) 2017 include preclinical analysis of copanlisib activity in B-cell lymphomas as a single agent or in combination with conventional and targeted agents and a study on the binding affinity of copanlisib.

Bayer is in discussion with the U.S. Food and Drug Administration (FDA) with respect to a New Drug Application (NDA), seeking accelerated approval of copanlisib for the treatment of relapsed or refractory FL who have received at least two prior therapies. The company has been granted Fast Track Designation by the FDA for copanlisib for this indication. Fast Track is a program designed to facilitate the development, and expedite the review of drugs to address unmet medical need in the treatment of a serious or life-threatening condition.

Copanlisib was also granted Orphan Drug Designation (ODD) by the FDA Office of Orphan Products Development in the U.S. in February 2015 for the treatment of FL and in February 2017 for the treatment of splenic, nodal, and extranodal subtypes of marginal zone lymphoma (MZL). The ODD program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and disorders. The FDA regards any disease that affects less than 200,000 patients in the U.S. as rare.

About CHRONOS-1
CHRONOS-1 is an open-label, single-arm Phase II study (ClinicalTrials.gov Identifier: NCT01660451) evaluating copanlisib as a monotherapy in non-Hodgkin’s lymphoma patients. CHRONOS-1 was designed to evaluate the efficacy and safety of copanlisib in patients with relapsed or refractory indolent NHL, including follicular lymphoma (FL), who received at least two prior therapies. The primary endpoint of CHRONOS-1 is the objective tumor response rate, with duration of response, overall survival, progression-free survival, quality of life, and safety serving as secondary endpoints.

About Non-Hodgkin’s Lymphoma
Non-Hodgkin’s Lymphoma (NHL) is the most common hematologic malignancy and the tenth most common cancer worldwide, with nearly 386,000 new cases diagnosed in 2012. It accounts for nearly 200,000 deaths per year worldwide. NHL comprises a highly heterogeneous group of diseases that can be indolent or aggressive with a poor prognosis. Follicular lymphoma is the most common histological subtype of indolent NHL, for which there is a need to improve treatment options.

About Copanlisib
Copanlisib is a novel pan-class I PI3K inhibitor with predominant inhibitory activity against PI3K-α and PI3K-δ isoforms, being developed by Bayer. The PI3K pathway is involved in cell growth, survival and metabolism, and its dysregulation plays an important role in non-Hodgkin’s lymphoma (NHL). Copanlisib is administered as a 1-hour infusion on an intermittent weekly basis (3 weeks on/1 week off).

Copanlisib has shown promising clinical activity in Phase I and Phase II studies in heavily pretreated patients with recurrent indolent and aggressive NHL. The broad clinical development program also includes Phase III studies in indolent NHL patients who have relapsed or are refractory to prior therapies. Information about these trials can be found at www.clinicaltrials.gov and www.chronostrials.com.

Copanlisib is not approved by the U.S. Food and Drug Administration, the European Medicines Agency or any other health authority.

ASTRAZENECA COMPLETES AGREEMENT WITH TERSERA THERAPEUTICS FOR COMMERCIAL RIGHTS TO ZOLADEX IN THE US AND CANADA

On March 31, 2017 AstraZeneca reported that it has completed the agreement with TerSera Therapeutics LLC for the commercial rights to Zoladex (goserelin acetate implant) in the US and Canada (Press release, AstraZeneca, MAR 31, 2017, View Source [SID1234518408]). Zoladex is an injectable luteinising hormone-releasing medicine, used to treat prostate cancer, breast cancer and certain benign gynaecological disorders. It was first approved in the US and Canada in 1989.

Under the terms of the agreement, AstraZeneca has received a payment of $250 million from TerSera for the commercial rights to the medicine in the US and Canada. As AstraZeneca will maintain a significant ongoing interest in Zoladex in the US and Canada, the payment will be reported as Externalisation Revenue in the Company’s financial statements, and will be booked in the first quarter of 2017.

AstraZeneca will receive future sales-related income through milestones totalling up to $70 million, as well as recurring quarterly sales-based payments at mid-teen percent of sales. AstraZeneca will also manufacture and supply Zoladex to TerSera, providing a further source of ongoing income from Zoladex in the US and Canada.

Spectrum Pharmaceuticals Highlights Three Abstracts on ROLONTIS™ (eflapegrastim) and BELEODAQ® (belinostat) for injection at the American Association for Cancer Research (AACR) Annual Meeting in Washington, D.C., April 1-5, 2017

On March 31, 2017 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported key presentations of clinical and scientific data related to its products at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held in Washington, D.C., from April 1-5, 2017 (Press release, Spectrum Pharmaceuticals, MAR 31, 2017, View Source [SID1234518393]).

The following ROLONTIS (eflapegrastim) related abstract is being presented at the AACR (Free AACR Whitepaper) meeting:

Monday, April 3, 2017:

Abstract # Type Title First Author Time
1347 Poster In vivo efficacy of eflapegrastim in rats with chemotherapy-induced neutropenia Kim 8:00 AM -12:00 PM

The following key BELEODAQ (belinostat) for injection related abstracts are being presented at the AACR (Free AACR Whitepaper) meeting:

Monday, April 3, 2017:

Abstract # Type Title First Author Time
1059 Poster Enhanced anti-tumor efficacy of a checkpoint inhibitor in combination with the HDAC inhibitor belinostat in a murine hepato-cellular carcinoma preclinical model Llopiz 8:00 AM-12:00 PM

2018 Poster Synergistic interactions between PLK1 and HDAC inhibitors in non-Hodgkin’s lymphoma cells occur in vitro and in vivo and proceed through multiple mechanisms Nguyen 1:00 PM-5:00 PM

For more information about the AACR (Free AACR Whitepaper) meeting and for a complete list of abstracts, please refer to the conference website at View Source!/4292.

IBRANCE® (palbociclib) Receives FDA Regular Approval and Expanded Indication for First-Line HR+, HER2- Metastatic Breast Cancer

On March 31, 2017 Pfizer Inc. (NYSE:PFE) reported that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for its first-in-class cyclin dependent kinase 4/6 (CDK 4/6) inhibitor, IBRANCE (palbociclib), based on the results from the confirmatory Phase 3 trial PALOMA-2 (Press release, Pfizer, MAR 31, 2017, View Source [SID1234518368]). The FDA action converts the accelerated approval of IBRANCE to regular approval and broadens the range of anti-hormonal therapy that may be administered with IBRANCE. IBRANCE now is indicated in combination with an aromatase inhibitor, expanding on its earlier indication in combination with letrozole, as initial endocrine based therapy in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer.

IBRANCE is the first CDK 4/6 inhibitor approved by the FDA. IBRANCE was granted accelerated approval in combination with letrozole in February 2015 and regular approval in February 2016 for a second indication: the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy. Today, IBRANCE plus letrozole is the most prescribed FDA-approved oral combination treatment for HR+, HER2- metastatic breast cancer.

"In the two years since its initial approval, IBRANCE has been prescribed to more than 50,000 patients by more than 9,800 physicians in the U.S.," said Liz Barrett, global president and general manager, Pfizer Oncology. "This important update to the IBRANCE label underscores the strength of the data we continue to generate for IBRANCE. We are proud of the impact this innovative medicine continues to have on patients’ lives."

The updated label is based on data including results from the Phase 3 PALOMA-2 trial, which evaluated IBRANCE as first-line therapy in combination with letrozole for postmenopausal women with estrogen receptor-positive (ER+), HER2- metastatic breast cancer. These data were published in the November 17, 2016 issue of The New England Journal of Medicine. PALOMA-2 demonstrated that the combination of IBRANCE and letrozole significantly extended progression-free survival (PFS), or the amount of time before tumor growth, compared with letrozole plus placebo. The median PFS of the IBRANCE and letrozole combination exceeded two years – making it the first treatment for this population of women to do so in a Phase 3 study. The median PFS for women treated with IBRANCE plus letrozole exceeded the median PFS for placebo plus letrozole by more than 10 months (24.8 months [95% CI, 22.1, not estimable] vs. 14.5 months [95% CI, 12.9, 17.1] for women treated with letrozole plus placebo (HR=0.58 [95% CI, 0.46, 0.72], p<0.0001)), and represented a 42% reduction in the risk of disease progression.

The warnings and precautions of IBRANCE include neutropenia and embryo-fetal toxicity. Adverse reactions in PALOMA-2 were generally consistent with the known adverse reaction profile for IBRANCE and no major unexpected safety findings were observed. The most common grade 3/4 adverse reactions with IBRANCE plus letrozole versus placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%) and anemia (5% vs 2%). Febrile neutropenia was reported in 2.5% of patients in the IBRANCE plus letrozole group and none of the patients in the placebo plus letrozole group.

Palbociclib (IBRANCE) is the only treatment for HR+, HER2- metastatic breast cancer with two category 1 recommendations from the National Comprehensive Care Network (NCCN). On March 13, the NCCN updated their recommendation for palbociclib plus letrozole as a first-line treatment for postmenopausal women with HR+, HER2- metastatic breast cancer to a category 1 recommendation.1 In addition, palbociclib plus fulvestrant is recommended (category 1) for postmenopausal women with HR+, HER2- metastatic breast cancer who have progressed on endocrine therapy or premenopausal women receiving a luteinizing hormone-releasing hormone (LHRH) agonist.1

The full prescribing information for IBRANCE can be found here.

IMPORTANT IBRANCE (palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg/day. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

IBRANCE has not been studied in patients with moderate to severe hepatic impairment or in patients withsevere renal impairment (CrCl <30 mL/min).

About IBRANCE (palbociclib) 125 mg capsules

IBRANCE is an oral inhibitor of CDKs 4 and 6,2 which are key regulators of the cell cycle that trigger cellular progression.3,4 In the U.S., IBRANCE is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy in postmenopausal women, or fulvestrant in women with disease progression following endocrine therapy.

Including the U.S., IBRANCE is approved in more than 60 countries.

Oncolytics Biotech® Inc.’s REOLYSIN® Provides Statistically Significant Improvement in Overall Survival in Canadian Cancer Trials Group Sponsored Randomized Phase 2 Study in Metastatic Breast Cancer

On March 31, 2017 Oncolytics Biotech Inc. (Oncolytics or the Company) (TSX:ONC) (OTCQX:ONCYF) reported the presentation of positive overall survival data from an open-label, randomized, Phase 2 study designed by the Canadian Cancer Trials Group (CCTG, formerly known as the National Cancer Institute of Canada – NCIC) (Press release, Oncolytics Biotech, MAR 31, 2017, View Source [SID1234518366]). The 74-patient study, powered to 90 percent, assesses the therapeutic combination of intravenously-administered REOLYSIN given in combination with paclitaxel versus paclitaxel alone in patients with advanced or metastatic breast cancer. Data from the study (IND 213), will be presented during the American Academy of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 1-5, in Washington, DC.

The abstract reports that in the intention-to-treat (ITT) patient population there was an improvement in median OS (secondary endpoint) from 10.4 months on the control arm to 17.4 months on the test arm (Hazard ratio 0.65, 80% CI 0.46-0.91, p=0.1), meeting the pre-specified significance level for the 90 percent powered study. Consistent with REOLYSIN acting as an immune therapy agent, there was no meaningful improvement in either progression free survival (the primary endpoint), or response rate (secondary endpoint). The Company is now planning a registration study in metastatic breast cancer with overall survival as the primary endpoint.

"This is the first controlled, randomized study where the systemic administration of an immuno-oncology viral agent (REOLYSIN), was well tolerated and had a significant impact on the overall survival of relapsed metastatic breast cancer patients when used in combination with paclitaxel," said Dr. Karen Gelmon, Head, Investigational Drug Program, Experimental Therapeutics, Department of Medical Oncology, British Columbia Cancer Agency.

"There is an emerging pattern, from this and other studies with REOLYSIN, where patients obtain significant benefit in overall survival, despite limited impact on response rates and/or progression-free survival," said Dr. Andres Gutierrez, Chief Medical Officer of Oncolytics. "This is a well-established pattern for other immunotherapies, like checkpoint inhibitors, which have been approved on an overall survival primary endpoint in melanoma, NSCLC and head and neck cancers. These phase 2 data also support the established mode of activity of REOLYSIN where selective cell lysis of permissive cancer cells is followed by an anti-tumor immune response, which may be responsible for the meaningful survival benefit for patients. Taking into account the specific findings from this study, we continue to believe that REOLYSIN is not solely an oncolytic agent, but has key attributes of an immuno-oncology agent as well."

The abstract, authored by Bernstein et al, "A randomized (RCT) phase II study of oncolytic reovirus (pelareorep) plus standard weekly paclitaxel (P) as therapy for metastatic breast cancer (mBC)" is now available on the AACR (Free AACR Whitepaper) website. CCTG will be making a poster presentation, #8466, at the AACR (Free AACR Whitepaper) Annual Meeting, on Tuesday Apr 4, 2017 from 1:00 PM – 5:00 PM, in Washington, DC.

Oncolytics would like to thank the patients that participated in this study, the CCTG and all the physicians and nurses involved.

About Breast Cancer
The American Cancer Society estimates there will be 255,180 new cases of breast cancer diagnosed in the United States and 41,070 deaths from the disease in 2017.