Lynparza Phase III SOLO-2 data demonstrate progression-free survival benefit in BRCA-mutated ovarian cancer as maintenance therapy

On March 14, 2017 AstraZeneca reported results from the Phase III SOLO-2 trial demonstrating a significant improvement in progression-free survival (PFS) in germline BRCA-mutated (gBRCA), platinum-sensitive, relapsed ovarian cancer patients treated with Lynparza (olaparib) tablets (300mg twice daily) compared with placebo in the maintenance setting (Press release, AstraZeneca, MAR 14, 2017, View Source [SID1234518106]). The trial met its primary endpoint of investigator assessed PFS (HR 0.30; 95% CI 0.22 to 0.41; P<0.0001; median 19.1 months vs 5.5 months).

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PFS as measured by Blinded Independent Central Review (BICR) evaluation, a pre-specified analysis supporting the primary endpoint, demonstrated a median PFS of 30.2 months vs 5.5 months for placebo, representing an improvement of 24.7 months (HR 0.25; 95% CI 0.18-0.35; P<0.0001).

Additionally, a statistically-significant benefit in time to second progression or death (PFS2) was also seen in patients treated with Lynparza (HR 0.50; 95% CI 0.34 to 0.72; P=0.0002; median not reached vs 18.4 months) compared with placebo, as well as improvements in other key secondary endpoints.

Progression-Free Survival by investigator and BICR assessment:

Analysis
Median progression-free survival, months
Hazard ratio
Investigator-assessed analysis
Lynparza
19.1

0.30 (95% CI, 0.22-0.41), P<0.0001
Placebo

5.5

Blinded Independent Central Review
Lynparza

30.2

0.25 (95% CI, 0.18-0.35), P<0.0001
Placebo

5.5

These results, presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in National Harbor, USA, build upon prior data in this setting, demonstrating the benefit of Lynparza as a maintenance therapy in relapsed ovarian cancer. Eric Pujade-Lauraine, Head of the Women Cancers and Clinical Research Department at Hôpitaux Universitaires Paris Centre, site Hôtel-Dieu, AP-HP and Principal Investigator of SOLO-2, said: "Today’s results are very encouraging, as they build upon previous trials examining Lynparza in platinum-sensitive relapsed BRCA-mutated ovarian cancer. Most importantly, patients were able to maintain quality of life while experiencing an impressive delay in disease progression, demonstrating the benefits of Lynparza tablets for these women whose cancer is often difficult to treat." Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "We are extremely pleased with the results from SOLO2, which support the potential benefit of Lynparza tablets as a maintenance therapy for patients with relapsed ovarian cancer. The tablet formulation may offer patients a reduced pill burden for Lynparza and a safety profile that is generally consistent with previous trials. We will work with regulatory authorities to make Lynparza tablets available to patients as quickly as possible." The safety profile for patients treated with Lynparza tablets during the trial was consistent to those observed with the currently-approved capsule formulation. Any adverse events (AE) Grade ≥3 were reported in 36.9% of patients treated with Lynparza and in 18.2% of patients who received placebo. The most common non-haematological AEs reported at a frequency of ≥20% were nausea (75.9% [grade ≥3, 2.6%]), fatigue/asthenia (65.6% [grade ≥3, 4.1%]), and vomiting (37.4% [≥3, 2.6%]). The most common haematological AEs reported in the Lynparza arm versus placebo were anaemia (43.6% [grade ≥3, 19.5%]), neutropenia (19.5% [grade ≥3, 5.1%]), and thrombocytopenia (13.8% [grade ≥3, 1.0%]). The 300mg twice-daily tablet dose reduces the pill burden for patients from sixteen capsules to four tablets per day.

NOTES TO EDITORS

About SOLO-2
SOLO-2 was a Phase III, randomised, double-blind, multicentre trial designed to determine the efficacy of Lynparza tablets as a maintenance monotherapy compared with placebo, in patients with platinum-sensitive relapsed or recurrent gBRCA-mutated (BRCAm) ovarian cancer. The trial, conducted in collaboration with the European Network for Gynaecological Oncological Trial Groups (ENGOT) and Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein (GINECO), randomised 295 patients with documented germline BRCA1 or BRCA2 mutations who had received at least 2 prior lines of platinum-based chemotherapy and were in complete or partial response. Eligible patients were randomised to receive 300mg Lynparza tablets twice daily or placebo tablets twice daily.

About Lynparza
Lynparza (olaparib) is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. It is approved by regulatory authorities in the EU and US for the treatment of women with BRCAm ovarian cancer. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of compounds targeting DNA damage response (DDR) mechanisms in cancer cells. In a previous study Lynparza capsules were shown to result in a significant improvement in PFS compared to placebo in platinum-sensitive, relapsed ovarian cancer (PSR OC) patients (HR 0.35; 95% CI 0.25-0.49; p <0.0001) as well as in the subgroup of patients whose tumours harbour BRCA mutations (HR 0.18; 95% CI 0.10-0.31; p <0.0001).

About ENGOT
ENGOT (European Network for Gynaecological Oncological Trial groups) is a research network of the European Society of Gynaecological Oncology (ESGO) and was founded in 2007. Currently, ENGOT consists of 19 cooperative groups from 15 European countries. ENGOT’s ultimate goal is to bring the best treatment to gynaecological cancer patients through the best science, and enabling every patient in every European country to access a clinical trial. ENGOT coordinates and promotes multinational clinical trials within Europe on patients with gynaecological cancer. This coordination is particularly relevant for academic clinical trials, translational research, research on rare diseases, and for clinical trials sponsored by the industry.

About GINECO
GINECO (Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein) is the French Cooperative Group in Oncology labelled by INCA (Institut National du Cancer or French NCI) for developing and conducting gynaecological and advanced breast cancer clinical trials at the national and international level. The network is nationwide with 700 specialized investigators belonging to more than 150 public or private oncology units. The GINECO group was founded in 1993 and is member of international consortia such as ENGOT and GCIG (Gynecologic Cancer InterGroup). GINECO was the ENGOT leading group for SOLO-2 trial.

10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

Scynexis has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Scynexis, 2017, MAR 13, 2017, View Source [SID1234521771]).

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10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

Bellicum Pharmaceuticals has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Bellicum Pharmaceuticals, MAR 13, 2017, View Source [SID1234518083]).

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Ipsen announces MHRA approval of new indication for Decapeptyl® for the treatment of pre-menopausal women with early stage breast cancer

On March 13, 2017 Ipsen (Euronext: IPN; ADR: IPSEY) reported that the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK, in coordination with fourteen other European regulatory agencies, has approved a new indication for Decapeptyl as adjuvant treatment in combination with tamoxifen or an aromatase inhibitor, of endocrine-responsive early-stage breast cancer in women at high-risk of recurrence who are confirmed as pre-menopausal after completion of chemotherapy (Press release, Ipsen, MAR 13, 2017, View Source [SID1234518221]).

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Alexandre Lebeaut, Executive Vice President, R&D, Chief Scientific Officer, Ipsen stated: "We are pleased to receive the first European approval which brings a new treatment option offering disease free survival benefit for high-risk pre-menopausal breast cancer patients. This is the result of a longstanding scientific collaboration between Ipsen and the IBCSG, one of the leading international cooperative groups in Breast Cancer which exemplifies Ipsen’s continuous commitment to improving patients care."

The approval is based on international trials sponsored by the International Breast Cancer Study Group (IBCSG) and conducted on a total of 5,700 randomized patients in 27 countries. Two randomized Phase 3 trials were conducted, SOFT (Suppression of Ovarian Function Trial) and TEXT (Tamoxifen and Exemestane Trial), which evaluated pre-menopausal women with early-stage hormone-receptor-positive breast cancer.

The IBCSG presented the combined results of the TEXT and SOFT clinical trials at the 2014 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting plenary session in Chicago and the 2014 San Antonio Breast Cancer Symposium. Results were published in the New England Journal of Medicine1;2.

On the basis of results from SOFT and TEXT studies, the international guidelines of St Gallen, the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper), the National Comprehensive Cancer Network (NCCN) and ASCO (Free ASCO Whitepaper) have been updated to recommend the use of ovarian function suppression with either tamoxifen or exemestane as a new therapeutic option for women at high risk of recurrence.

Meredith M. Regan, Associate Professor in the Department of Biostatistics and Computational Biology at the Dana-Farber Cancer Institute, Associate Professor of Medicine at Harvard Medical School, IBCSG Group Statistician, commented: "IBCSG initiated those 2 prospective studies SOFT and TEXT more than fifteen years ago with the ambitious goal to address a major question on the role of OFS in the adjuvant setting for premenopausal women. We are very happy that these studies have been the foundation for a MHRA approval of triptorelin which will facilitate patient’s access to this new treatment paradigm. We thank Ipsen for their support since the beginning of those studies".

Cambridge-based Astex Pharmaceuticals Celebrates as Cancer Drug Receives US Marketing Approval

On March 13 2017 Astex Pharmaceuticals ("Astex"), a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system, reported that its long-standing pharmaceutical collaborator, Novartis, has received US Food and Drug Administration (FDA) marketing approval for Kisqali (ribociclib, formerly known as LEE011) plus an aromatase inhibitor as a first-line treatment in post-menopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced (metastatic) breast cancer (Press release, Astex Pharmaceuticals, MAR 13, 2017, View Source [SID1234518119]).

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Astex is eligible to receive a milestone payment in respect of this FDA marketing approval and on approval of additional regulatory filings in Europe and Japan, as well as royalty payments on annual sales of Kisqali, under the drug discovery alliance entered into between Astex and Novartis in 2005. The partnership was struck to discover cell cycle inhibitors which represented a novel class of compounds that target the mechanisms of cell division in order to prevent or interfere with cancer growth.

Under the collaboration, Astex scientists, based at the company’s research laboratories in Cambridge UK, were responsible for solving the crystal structure of the key cancer target protein CDK4. This was an important scientific breakthrough that no other group had previously been able to achieve, leading to a peer-reviewed publication in PNAS[1]. Working with the Novartis team at the Novartis Institutes for BioMedical Research (NIBR), Cambridge, Mass., USA, Astex then applied its structure-based drug discovery technology, part of its Pyramid platform, in the collaboration that led to the discovery of LEE011, (now known as Kisqali) which was then taken forward by Novartis into clinical trials. In total, a team of some 25 Astex scientists were involved in this research program.

Kisqali (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drug that helps slow the progression of cancer by inhibiting two proteins (CDK4 & CDK6) which, when over-activated, can enable cancer cells to grow and divide quickly.

Novartis received the approval under the FDA Breakthrough Therapy Designation and Priority Review programs, based on data from a first-line Phase III trial that met its primary endpoint at interim analysis, due to its superior efficacy compared to letrozole alone. The combination of Kisqali plus letrozole reduced the risk of disease progression or death by 44% over letrozole alone. There was a sustained separation of the progression free survival curves evident as early as 8 weeks and more than 53% of patients with measurable disease who took Kisqali plus letrozole saw their tumour size shrink by at least 30%. The combination also showed significant clinical benefit in all patient subgroups regardless of disease burden or tumour location[2].

Harren Jhoti, President and CEO of Astex, UK, said, "We’re committed to the fight against cancer and so we are absolutely delighted that Novartis has received this first approval of a cancer drug arising from our productive collaboration. This milestone further validates the power of our Pyramid platform and the excellence of our science. It’s a moment to celebrate when such ground-breaking scientific work results in a new treatment option for women with advanced breast cancer."

Astex was formed in 1999 in Cambridge, UK, and was a pioneer in the development of fragment-based drug discovery technology. Backed by leading venture capital firms, including Abingworth, it has established multiple partnerships with major pharmaceutical companies including AstraZeneca, Janssen (Johnson & Johnson) and GSK as well as Novartis to use the Company’s drug discovery platform, Pyramid, to identify novel small molecule drugs addressing key disease targets. Today it is a wholly-owned subsidiary of Otsuka Pharmaceutical Co. Ltd., Tokyo, Japan, with a focus on cancer and diseases of the central nervous system. It employs about 200 staff at its research headquarters in Cambridge UK and its clinical development headquarters in Pleasanton, California, USA.