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Novartis Kisqali® (ribociclib, LEE011) receives FDA approval as first-line treatment for HR+/HER2- metastatic breast cancer in combination with any aromatase inhibitor

On March 13, 2017 Novartis reported that the US Food and Drug Administration (FDA) has approved Kisqali (ribociclib, formerly known as LEE011) in combination with an aromatase inhibitor as initial endocrine-based therapy for treatment of postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer (Press release, Novartis, MAR 13, 2017, View Source [SID1234518102]).

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Kisqali is a CDK4/6 inhibitor approved based on a first-line Phase III trial that met its primary endpoint early, demonstrating statistically significant improvement in progression-free survival (PFS) compared to letrozole alone at the first pre-planned interim analysis[1]. Kisqali was reviewed and approved under the FDA Breakthrough Therapy designation and Priority Review programs.

"Kisqali is emblematic of the innovation that Novartis continues to bring forward for people with HR+/HER2- metastatic breast cancer," said Bruno Strigini, CEO, Novartis Oncology. "We at Novartis are proud of the comprehensive clinical program for Kisqali that has led to today’s approval and the new hope this medicine represents for patients and their families."

The FDA approval is based on the superior efficacy and demonstrated safety of Kisqali plus letrozole versus letrozole alone in the pivotal Phase III MONALEESA-2 trial. The trial, which enrolled 668 postmenopausal women with HR+/HER2- advanced or metastatic breast cancer who received no prior systemic therapy for their advanced breast cancer, showed that Kisqali plus an aromatase inhibitor, letrozole, reduced the risk of progression or death by 44 percent over letrozole alone (median PFS not reached (95% CI: 19.3 months-not reached) vs. 14.7 months (95% CI: 13.0-16.5 months); HR=0.556 (95% CI: 0.429-0.720); p<0.0001)[1].

More than half of patients taking Kisqali plus letrozole remained alive and progression free at the time of interim analysis, therefore median PFS could not be determined[1]. At a subsequent analysis with additional 11-month follow-up and progression events, a median PFS of 25.3 months for Kisqali plus letrozole and 16.0 months for letrozole alone was observed[2]. Overall survival data is not yet mature and will be available at a later date.

"In the MONALEESA-2 trial, ribociclib plus letrozole reduced the risk of disease progression or death by 44 percent over letrozole alone, and more than half of patients (53%) with measurable disease taking ribociclib plus letrozole experienced a tumor burden reduction of at least 30 percent. This is a significant result for women with this serious form of breast cancer," said Gabriel N. Hortobagyi, MD, Professor of Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center and MONALEESA-2 Principal Investigator. "These results affirm that combination therapy with a CDK4/6 inhibitor like ribociclib and an aromatase inhibitor should be a new standard of care for initial treatment of HR+ advanced breast cancer."

Kisqali is taken with or without food as a once-daily oral dose of 600 mg (three 200 mg tablets) for three weeks, followed by one week off treatment. Kisqali is taken in combination with four weeks of any aromatase inhibitor[1].

Breast cancer is the second most common cancer in American women[3]. The American Cancer Society estimates more than 250,000 women will be diagnosed with invasive breast cancer in 2017[3]. Up to one-third of patients with early-stage breast cancer will subsequently develop metastatic disease[4].

Novartis is committed to providing patients with access to medicines, as well as resources and support to address a range of needs. The Kisqali patient support program is available to help guide eligible patients through the various aspects of getting started on treatment, from providing educational information to helping them understand their insurance coverage and identify potential financial assistance options. For more information, patients and healthcare professionals can call 1-800-282-7630.

The full prescribing information for Kisqali can be found at View Source

About Kisqali (ribociclib)
Kisqali (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

About the MONALEESA Clinical Trial Program
Novartis is continuing to assess Kisqali through the robust MONALEESA clinical trial program, which includes two additional Phase III trials, MONALEESA-3 and MONALEESA-7, that are evaluating Kisqali in multiple endocrine therapy combinations across a broad range of patients, including premenopausal women. MONALEESA-3 is evaluating Kisqali in combination with fulvestrant compared to fulvestrant alone in postmenopausal women with HR+/HER2- advanced breast cancer who have received no or a maximum of one prior endocrine therapy. MONALEESA-7 is investigating Kisqali in combination with endocrine therapy and goserelin compared to endocrine therapy and goserelin alone in premenopausal women with HR+/HER2- advanced breast cancer who have not previously received endocrine therapy.

Mylan Launches Generic Aromasin® Tablets

On March 13, 2017 Mylan N.V. (NASDAQ, TASE: MYL), reported the U.S. launch of Exemestane Tablets, 25 mg, a generic version of the reference listed drug, Pfizer’s Aromasin Tablets (Press release, Mylan, MAR 13, 2017, View Source [SID1234518093]). Mylan received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for this product, which is indicated in the treatment of certain types of breast cancer in women after menopause.

Mylan is the largest supplier of cancer medicines by volume in the U.S., and the launch of Exemestane Tablets, 25 mg, adds to the company’s robust oncology franchise. Exemestane Tablets, 25 mg, had U.S. sales of approximately $100 million for the 12 months ending Jan. 31, 2017, according to IMS Health.

Currently, Mylan has 240 ANDAs pending FDA approval representing approximately $100.8 billion in annual brand sales, according to IMS Health. Forty-five of these pending ANDAs are potential first-to-file opportunities, representing $39 billion in annual brand sales, for the 12 months ending Dec. 31, 2016, according to IMS Health.

Expansion of Phase I/II trial evaluating lirilumab in combination with Opdivo (nivolumab) in patients with advanced solid tumors

On March 13, 2017 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported that its partner Bristol-Myers Squibb has amended the clinical trial protocol for its ongoing Phase I/II trial evaluating the safety and tolerability of lirilumab in combination with Opdivo in patients with advanced refractory solid tumors (Press release, Innate Pharma, MAR 13, 2017, View Source [SID1234518092]).

Under the amended protocol, updated on clinicaltrials.gov, the study will expand in scope to include additional cohorts of Opdivo plus lirilumab in solid tumors, including a randomized cohort exploring Opdivo with or without lirilumab in platinum refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), and initial testing of the triplet combination of Opdivo, Yervoy and lirilumab in solid tumors.

The protocol amendment follows the presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting (SITC, November 2016) of an interim efficacy analysis, which showed encouraging preliminary clinical benefit in the cohort of patients with advanced platinum refractory SCCHN in this Phase I/II trial.

Pierre Dodion, MD, Chief Medical Officer at Innate Pharma, said: "This trial expansion builds on the promising preliminary signs of efficacy which we have seen in lirilumab in the initial cohort of patients in the Phase I/II study, announced at the SITC (Free SITC Whitepaper) annual meeting last year. We are very encouraged by these signs and are delighted that our partner Bristol-Myers Squibb is exploring lirilumab’s potential further through this large scale and broad-ranging trial."

Lirilumab is directed against the inhibitory killer-cell immunoglobulin-like receptors (KIRs) expressed predominantly on natural killer (NK) cells, which belong to the innate immune system. It is licensed to Bristol-Myers Squibb and is being studied for its potential in combination with Opdivo and/or Yervoy, which are immune checkpoint inhibitors that respectively block the PD-1 and CTLA-4 receptors on T cells.

Lirilumab is being investigated in a broad exploratory program sponsored by Bristol-Myers Squibb, in various combinations with other agents across a range of solid and hematological cancer indications (see on clinicaltrials.gov).

About the Study
CA223-001 is a Phase I/II trial designed to assess the safety, tolerability and preliminary anti-tumor activity of the combination of lirilumab (anti-KIR) and Opdivo (anti-PD-1) or lirilumab and Opdivo with Yervoy (anti-CTLA-4) in advanced refractory solid tumors. The study cohorts include dose escalation and initial signal detection in multiple solid tumors; safety and preliminary efficacy data were presented at the 2016 ESMO (Free ESMO Whitepaper)* and SITC (Free SITC Whitepaper) meetings.

Key study endpoints include safety and tolerability, best overall response (BOR), objective response rate (ORR), duration of response (DOR) and biomarker assessments.

Heat Biologics Meets Efficacy Endpoint in its Phase 1b Lung Cancer Trial to Progress to Phase 2

On March 13, 2017 Heat Biologics, Inc. ("Heat") (Nasdaq:HTBX), a leader in the development of immunotherapies designed to activate a patient’s immune system against cancer, reported that the company achieved the efficacy endpoint for its Phase 1b trial evaluating HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo), for the treatment of non-small cell lung cancer (NSCLC) and that the trial met the expansion criteria to advance into a Phase 2 (Press release, Heat Biologics, MAR 13, 2017, View Source [SID1234518090]).

In reviewing the Phase 1b data, the Data Monitoring Committee (DMC) determined that the Phase 1b safety endpoint was met and that there do not appear to be additional toxicities seen in the HS-110/nivolumab combination compared to existing data on nivolumab alone. Furthermore, 5 out of 15 patients treated with the HS-110/nivolumab combination had 20% or greater tumor reduction. The DMC concluded that the positive safety profile, mechanistic evidence and encouraging signs of synergistic efficacy warranted expansion to a Phase 2 trial.

"We are encouraged by the results from this Phase 1b trial evaluating the therapeutic vaccine, HS-110, combined with the checkpoint inhibitor, nivolumab, in patients with advanced non-small cell lung cancer," said Daniel Morgensztern, M.D., Associate Professor of Medicine and Director of Thoracic Oncology, Washington University School of Medicine. "We continue to see that the combination appears to be generally well-tolerated, and the encouraging signs of efficacy warrant a larger sample size. We’ve seen some patients with increased tumor infiltrating lymphocytes (TIL) after treatment, and anticipate that we can confirm this trend in the Phase 2."

"We are pleased with the DMC’s decision to expand the trial to a Phase 2 given the positive clinical responses seen to-date. We saw that those patients with increased levels of TIL at 10 weeks had a durable benefit, with six out of eight of these patients (75%) alive at the one-year follow-up point," said Jeff Hutchins, Ph.D., Heat’s Chief Scientific Officer and Senior Vice President of Preclinical Development. "We designed this trial with the Bristol-Myers Squibb Checkmate 057 nivolumab trial in mind, which reported a 19% response rate in a similar patient population. Although this is a small sample size and a non-randomized trial, we believe that this is an encouraging sign that the combination may be more effective than checkpoint therapy alone and could provide therapeutic benefit to a majority of lung cancer patients who do not respond well to checkpoint monotherapy. We remain focused on enrolling new patients to better characterize the objective response rate, durability of the response and associated immune activity."

SBI Pharma and Chugai Enter an Agreement of Exclusive Marketing Rights for “ALAGLIO® Granule 1.5g” in Japan

On March 13, 2017 SBI Pharmaceuticals Co., Ltd. (Head Office: Minato-ku, Tokyo; Representative Director and President: Yoshitaka Kitao; "SBI Pharma"), a subsidiary of SBI Holdings, Inc., engaged in the research and development of medicines using 5-ALA* (5-Aminolevulinic acid), reported that it has entered a licensing agreement with Chugai Pharmaceutical Co., Ltd. (Head Office: Chuo-ku, Tokyo; Chairman & CEO: Osamu Nagayama; "Chugai") to grant Chugai the exclusive marketing rights of "ALAGLIO Granule 1.5g ("ALAGLIO")" in Japan for visualizing tumor tissues during resection of bladder cancer (Press release, Chugai, MAR 13, 2017, View Source [SID1234518088]). The approval for manufacture and marketing of ALAGLIO is under application.

In a surgical procedure to remove bladder cancer called TURBT** (TransUrethral Resection of Bladder Tumor), the key is discerning cancer tissues from normal tissues and removing all the cancerous tumors only. By orally administering ALAGLIO to a patient three hours before surgery and shedding a blue excitation light on the lesion during the surgery, the cancerous portion emits red fluorescence, thereby making it easier to distinguish between cancer and normal tissues.

Through the exclusive marketing agreement, SBI Pharma and Chugai join and further strengthen the effort to speed the availability of ALAGLIO, a new therapeutic option, for patients fighting against bladder cancer and healthcare professionals.

* 5-aminolevulinic acid (5-ALA)
An amino acid produced in mitochondria. It is an important substance that serves as a functional molecule related to energy production in the form of heme and cytochromes, and its productivity is known to decrease with age. 5-ALA is contained in food such as shochu lees, red wine and Asian ginseng. It is also known as a material forming chloroplasts in plants.

** Transurethral resection of bladder tumor (TURBT)
TURBT is a method to insert a surgical endoscope from the urethra without laparotomy, and resect the tumor while preserving the bladder function.