The ODAC meeting is scheduled for
The efficacy and safety of Lynparza in combination with abiraterone and prednisone or prednisolone have been demonstrated in the PROpel Phase III trial, first presented at the 2022
Lynparza in combination with abiraterone and prednisone or prednisolone is approved in the EU and several other countries for the treatment of adult patients with mCRPC based on the PROpel trial.
Notes
Prostate cancer
Prostate cancer is the second most commonly diagnosed cancer in men and the fifth leading cause of cancer death in men globally, with an incidence of 1.4 million and 375,000 deaths in 2020.1,2,3 In
Metastatic castration-resistant prostate cancer
Metastatic prostate cancer is associated with a significant mortality rate.12 Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.13
In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.14 Approximately 10-20% of men with advanced prostate cancer will develop castration-resistant prostate cancer (CRPC) within five years, and at least 84% of these men will have metastases at the time of CRPC diagnosis.14 Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.14
Despite the advances in mCRPC treatment in the past decade with taxane and new hormonal agent (NHA) treatment, there is high unmet need in this population.14-17
PROpel
PROpel is a randomised, double-blind, multi-centre Phase III trial testing the efficacy, safety, and tolerability of Lynparza versus placebo when given in combination with abiraterone, as well as prednisone or prednisolone, in men with mCRPC who had not received prior chemotherapy or NHAs in the mCRPC setting.
The primary endpoint is rPFS and secondary endpoints include OS, time to secondary progression or death, and time to first subsequent therapy.
In the PROpel Phase III trial, Lynparza is combined with abiraterone, an NHA which targets the androgen receptor (AR) pathway. AR signalling engages a transcriptional programme that is critical for tumour cell growth and survival in prostate cancer.18,19 In addition, the AR also plays a role in repairing DNA damage in prostate cancer cells, including damage not normally repaired by homologous recombination repair (HRR). Preclinical models have suggested a number of potential mechanisms that could account for increased combination efficacy in both HRR deficient and HRR proficient prostate cancer.20-26 Recent data provide evidence that PARP facilitates AR-DNA binding in the presence of DNA damage (AZ internal data on file) and that combined inhibition of PARP with olaparib and AR activity with an NHA results in enhanced DNA damage and anti-tumour activity in non-HRRm prostate cancer models.21,24,26,27,28
For more information about the trial please visit ClinicalTrials.gov.
Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in HRR, such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as NHAs).
Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death.
Lynparza is currently approved in a number of countries across multiple tumour types including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for gBRCAm, HER2-negative metastatic breast cancer (in the EU and
Lynparza, which is being jointly developed and commercialised by
The
In
Working together, the companies will develop Lynparza and Koselugo and other potential new medicines as monotherapies and as combinations. The companies will also develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines independently.
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that
Contacts
For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.
References
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2. Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019; 10(2):63-89.
3. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249.
4. Cancer.Org. Key Statistics For Prostate Cancer. Available at https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html. Accessed
5. Ng K, et al. Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Advances and Treatment Strategies in the First-
6. George DJ, et al. Treatment Patterns and Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer in a Real-World Clinical Practice Setting in
7. de
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21. Asim M, et al. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer. Nature. 2017;8:374.
22. Polkinghorn WR, et.
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