Novartis continues to push the boundaries of innovation, reimagining medicine, with bold science as it today unveils strong presence at ASCO, including overall survival data in prostate and breast cancer

• Compelling data demonstrate Novartis’ unwavering commitment to reimagining cancer care for patients in the UK with prostate cancer, advanced breast cancer, lung cancer, melanoma and neuroendocrine tumours

• ¹⁷⁷Lu-PSMA-617 significantly improves overall survival (OS) and radiographic progression-free survival (rPFS) for men with late stage advanced prostate cancer in Phase III VISION^[i]

• Kisqali® (ribociclib) in combination with fulvestrant reports longest median overall survival in CDK4/6 inhibitor trials for postmenopausal HR+/HER2- metastatic breast cancer patients from an exploratory analyses of the MONALEESA-3 trial^[ii]

• Lutathera® (lutetium (¹⁷⁷Lu) oxodotreotide) final OS data from Phase III NETTER-1 study in adults with somatostatin receptor-positive midgut neuroendocrine tumors^[iii]

London, UK, 3 June 2021 — Novartis has today announced encouraging new data at the American Society of Clinical Oncology (ASCO) Annual Meeting from its portfolio of approved and investigational therapies aimed at transforming the lives of people living with cancer. As the only pharmaceutical company pursuing a four-platform strategy that harnesses targeted therapies, radioligand therapy (RLT), cell and gene therapy, and immunotherapy, Novartis are on a relentless pursuit to secure the best outcomes for cancer patients in the UK.

“Our bold ambition is driven by our passion for patients and our mission to extend and improve the lives of those living with cancer and serious blood disorders, and ultimately find cures,” said Mari Scheiffele, Novartis Oncology General Manager, UK & Ireland. “These exciting data from across our four therapeutic platforms, notably the overall survival data in prostate and advanced breast cancer, illustrate how we are uniquely positioned to deliver transformative innovations that may bring renewed hope for UK patients.”

Key highlights of the data being presented at ASCO centre around the updated Phase III radioligand therapy study VISION, an investigational therapy for people living with with metastatic castration-resistant prostate cancer and around updated overall survival data for Kisqali (ribociclib) in combination with fulvestrant in the MONALEESA 3 trial. In the UK, around 55,000 women are diagnosed with breast cancer each year.^[iv] 30% of women with earlier stages of breast cancer will develop advanced disease.^[v] Yet worryingly, prostate cancer has overtaken breast cancer to become the third most common cause of cancer death in the UK after lung and colorectal cancer.^[vi]

The Phase III VISION study is evaluating the efficacy and safety of ¹⁷⁷Lu-PSMA-617, a targeted RLT plus best standard of care in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had already been treated with taxane and androgen pathway inhibitors, compared to best standard of care alone. The trial met both primary endpoints with men who received ¹⁷⁷Lu-PSMA-617 plus best standard of care achieving a 38% reduction in risk of death (median OS benefit of 4 months) and a 60% reduction in the risk of radiographic disease progression or death (median rPFS benefit of 5 months) compared to best standard of care alone^[1]. Results from the VISION trial [Abstract #LBA4] will be presented at a plenary session at the congress on Sunday, 6 June at 18.00 BST (13:00 EDT) and included in an upcoming EU regulatory submission.

“Men with metastatic prostate cancer have about a 3 in 10 chance of surviving 5 years^[vii] and need new treatment options. These data from the first Phase III study of a radioligand therapy in this advanced prostate cancer setting confirm the potential of ¹⁷⁷Lu-PSMA-617 targeted therapy to improve clinical outcomes,” said Alessandra Dorigo, General Manager UK, Ireland, Baltics and Nordics in Novartis Advanced Accelerator Applications (AAA). “With more than 15 dedicated early to late development and research programmes underway, our comprehensive development programme will continue to explore targeted radioligand therapy, in prostate and across a number of tumour types.”

The Phase III MONALEESA-3 trial is analysing the efficacy and safety of treating postmenopausal women with HR+/HER2- advanced breast cancer (ABC) with fulvestrant +/- ribociclib.^[ii] In this study the ribociclib arm demonstrated statistically significant longer median OS when compared with the placebo arm. The updated exploratory analysis of MONALEESA-3 trial presented at ASCO 2021 reported the longest OS benefit seen in a CDK4/6 inhibitor + fulvestrant in this population of women to date.^[ii] Which adds further strength to the data. In this updated analysis, the need for chemotherapy was delayed by 4 years (48.1 months) in patients taking Kisqali in combination with fulvestrant and 28.8 months in the patients taking fulvestrant alone (HR=0.70; 95% CI: 0.57-0.88). Adverse events were consistent with previously reported Phase III trial results^[ii]

These data [Abstract #1001] will be presented at a plenary session at the congress on Saturday, 5 June at 18.30 BST (13.30 EDT).

Novartis has over 30 years of heritage in oncology, spanning back to the approval of the first targeted therapy and beyond, transforming the lives of people living with cancer and life-threatening blood disorders. Novartis’ bold ambition is grounded in its industry-leading oncology and haematology pipeline of more than 45 different compounds across 70+ development programmes. The ongoing research potentially offers renewed hope for these patients who have limited or inadequate treatment options, as we reimagine medicine.

 About Kisqali^® (ribociclib)^[viii]

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 rapidly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.

Ribociclib is approved for use in the UK for the treatment of women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy. In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinising hormone-releasing hormone (LHRH) agonist.

Ribociclib can be 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. Ribociclib is taken in combination with four weeks of any aromatase inhibitor, or with 500 mg of fulvestrant that should be given by intramuscular injection on Days 1, 15, 29, and once monthly thereafter. Please refer to the SmPC of ribociclib for additional details.

About MONALEESA-3^[ix]

MONALEESA-3 was a randomised, double-blind, placebo-controlled, multi-centre, phase III trial in postmenopausal women with HR+/HER2- mBC who received no or only 1 prior line of endocrine therapy for advanced disease, and those who had had a relapse during or within 12 months after completion of adjuvant or neoadjuvant endocrine therapy. Patients (N=726) were stratified by the presence of liver and/or lung metastases and prior endocrine therapy. Patients were randomised (2:1) to receive either KISQALI 600 mg oral (3 weeks on, 1 week off) and fulvestrant 500 mg (intramuscular injection on Days 1, 15, 29, and once monthly thereafter) or placebo (3 weeks on, 1 week off) and fulvestrant 500 mg (intramuscular injection on Days 1, 15, 29, and once monthly thereafter). The primary end point was investigator assessed progression free survival. Secondary end points included overall survival, overall response rate, clinical benefit rate, and safety.

About Phenotypic Precision Medicine in Advanced Prostate Cancer

Despite advances in prostate cancer care, there is a high unmet need for new targeted treatment options to improve outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC). There are around 48,500 new prostate cancer cases in the UK every year, (2015-2017)^[x], making it the most commonly diagnosed cancer in the UK. The five-year survival rate for patients with mCRPC is approximately 15%.^[xi]

More than 80% of prostate cancer tumours highly express a phenotypic biomarker^[xii] called Prostate Specific Membrane Antigen (PSMA)^{[xiii],[xiv],[xv],[xvi],[xvii]}, making it a promising diagnostic (through positron emission tomography (PET) scan imaging) and therapeutic target for radioligand therapy.^[xviii]

About ¹⁷⁷Lu-PSMA-617

¹⁷⁷Lu-PSMA-617 is an investigational PSMA-targeted radioligand therapy for metastatic castration-resistant prostate cancer. It is a type of precision cancer treatment combining a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle).^[xix],[xx]^,[xxi] After administration into the bloodstream, ¹⁷⁷Lu-PSMA-617 binds to prostate cancer cells that express PSMA^[xxii], a transmembrane protein, with high tumour-to-normal tissue uptake.^19,[xxiii]^,[xxiv] Once bound, emissions from the radioisotope damage tumour cells, disrupting their ability to replicate and/or triggering cell death.^{[xxv],[xxvi],[xxvii]} The radiation from the radioisotope works over very short distances to limit damage to surrounding cells.^18,19,23

About VISION

VISION is an international, prospective, randomised, open-label, multicenter, Phase III study to assess the efficacy and safety of ¹⁷⁷Lu-PSMA-617 (7.4 GBq administered by i.v. infusion every 6 weeks for a maximum of 6 cycles) plus investigator-chosen best standard of care in the investigational arm, versus best standard of care in the control arm^[xxviii]. Patients with PSMA PET-scan positive mCRPC, and progression after prior taxane and androgen receptor- pathway inhibitors were randomised in a 2:1 ratio in favour of the investigational arm. The alternate primary endpoints were rPFS and OS.²⁸ The study enrolled 831 patients.¹

About Novartis 

Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach more than 750 million people globally and we are finding innovative ways to expand access to our latest treatments. About 105 000 people of more than 140 nationalities work at Novartis around the world. Find out more at www.novartis.com. 

In the UK, we employ approximately 1,300 people to serve healthcare needs across the whole of the UK, as well as supporting the global operations of Novartis. Since 2014, Novartis has invested over £200 million in R&D and is the single largest industry sponsor of clinical trials in the UK. For more information, please visit www.novartis.co.uk                                                                                                                                                                                                                                                      

Novartis UK is on Twitter. Sign up to follow @NovartisUK at www.twitter.com/novartisuk

UK | JUNE 2021 | MLR ID 128719

 

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References

1 Novartis data on file

2 Slamon D, Neven P, Chia S, et al, Updated overall survival (OS) results from the Phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2− advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, June 5, 2021, (Abstract #1001).

3 Novartis data on file

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[v] O'Shaughnessy J. Extending survival with chemotherapy in metastatic breast cancer. The Oncologist. October 2005, 10(suppl.): 20-29

[vi] Cancer Research UK [online]. Cancer mortality for common cancers. Available from  https://www.cancerresearchuk.org/health-professional/cancer-statistics/mortality/common-cancers-compared#heading-Zero [Accessed June 2021]

[vii] SEER. Cancer stat facts: prostate cancer April 2021.

[https://seer.cancer.gov/statfacts/html/prost.html] [Accessed June 2021].

[viii] Summary of Product Characteristics (SPC). emc website: https://www.medicines.org.uk/emc/product/8110. [Accessed June 2021].

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[x] Cancer Research UK ([Online]), Prostate cancer survival statistics. Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/prostate-cancer#heading-One [Accessed June 2021].

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[xii] Sant GR, Knopf KB, Albala DM. Live-single-cell phenotypic cancer biomarkers-future role in precision oncology? NPJ Precision Oncology 2017;1(1):21

[xiii] Hupe MC, Philippi C, Roth D, et al. Expression of prostate-specific membrane antigen (PSMA) on biopsies is an independent risk stratifier of prostate cancer patients at time of initial diagnosis. Front Oncol 2018;8:623.

[xiv] Bostwick DG, Pacelli A, Blute M, et al. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer 1998;82(11):2256–61

[xv] Pomykala KL, Czernin J, Grogan TR, et al. Total-body 68Ga-PSMA-11 PET/CT for bone metastasis detection in prostate cancer patients: potential impact on bone scan guidelines. J Nucl Med 2020;61(3):405–11

[xvi] Minner S, Wittmer C, Graefen M, et al. High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate 2011;71(3):281–8

[xvii] Hope TA, Aggarwal R, Chee B, et al. Impact of 68Ga-PSMA-11 PET on management in patients with biochemically recurrent prostate cancer. J Nucl Med 2017;58(12):1956–61

[xviii] Hofman MS, Violet J, Hicks RJ et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol 2018;19(6):825–33

[xix] Kratochwil C, Giesel FL, Stefanova M, et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-labeled PSMA-617. J Nucl Med 2016;57(8):1170–6. [https://pubmed.ncbi.nlm.nih.gov/26985056/] [Accessed June 2021].

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[xxi] Benešová M, Schäfer M, Bauder-Wüst U, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med 2015;56(6):914–20

[xxii] Haberkorn U, Eder M, Kopka K, et al. New Strategies in Prostate Cancer: Prostate-Specific Membrane Antigen (PSMA) Ligands for Diagnosis and Therapy. Clin Cancer Res 22(1):9-15.2016

[xxiii] Violet J, Jackson P, Ferdinandus J et al. Dosimetry of (177)Lu-PSMA-617 in metastatic castration-resistant prostate cancer: correlations between pretherapeutic imaging and whole-body tumor dosimetry with treatment outcomes. J Nucl Med 2019;60(4):517–23

[xxiv] Current K, Meyer C, Magyar CE et al. Investigating PSMA-targeted radioligand therapy efficacy as a function of cellular PSMA levels and intra-tumoral PSMA heterogeneity. Clin Cancer Res 2020;26(12):2946–55.

[xxv] Kassis A. Therapeutic Radionuclides: Biophysical and Radiobiologic Principles. Semin Nucl Med. 2008; 38(5): 358–366

[xxvi] Fendler W, Stuparu A, et al. Establishing 177Lu-PSMA-617 Radioligand Therapy in a Syngeneic Model of Murine Prostate Cancer. J Nucl Med 2017; 58: 1786–1792

[xxvii] Ruigrok E, van Vliet N, et al. Extensive preclinical evaluation of lutetium-177-labeled PSMA-specific tracers for prostate cancer radionuclide therapy. Eur J Nucl Med Mol Imaging. 2020; 48: 1339-1350

[xxviii] Sartor AO, Morris MJ, Krause BJ. VISION: an international, prospective, open-label, multicenter, randomized phase 3 study of 177Lu-PSMA-617 in the treatment of patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol 2019;37(15 suppl):TPS5099