Phase III (INAVO120) results show that inavolisib in combination with palbociclib and fulvestrant significantly improved progression-free survival in the first-line setting Data will be shared with health authorities and presented at an upcoming medical meeting
Basel, 5 December 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today positive results from the Phase III INAVO120 study of the investigational therapy, inavolisib, in combination with palbociclib (Ibrance®) and fulvestrant as a potential first-line treatment option for people with PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, endocrine-resistant, locally advanced or metastatic breast cancer. The study met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant and clinically meaningful improvement compared to palbociclib and fulvestrant alone. Overall survival data were immature at this time, but a clear positive trend has been observed. Follow-up will continue to the next analysis. "These pivotal study results for this inavolisib combination could represent a transformative medical advance for people with PIK3CA-mutated HR-positive breast cancer," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "We look forward to expanding our portfolio of breast cancer medicines into the HR-positive space and bringing this potentially best-in-class new treatment option to patients as quickly as possible." The inavolisib combination was well tolerated and adverse events were consistent with the known safety profiles of the individual study treatments, with no new safety signals observed. Inavolisib is an oral therapy with high in vitro potency and selectivity for PI3Kα inhibition and the ability to specifically trigger the breakdown of mutant PI3Kα protein. With this unique dual mechanism of action, inavolisib may provide well-tolerated, durable disease control and potentially improved outcomes for people with HR-positive/HER2-negative, PIK3CA-mutated advanced breast cancer. PIK3CA mutations can lead to mutated PI3Kα protein which contributes to uncontrolled tumour growth, disease progression and resistance to endocrine-based treatment.3,4 About the INAVO120 study5
The study included 325 patients, who were randomly assigned to either the investigational or control treatment arm. The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomisation in the clinical trial to the time when the disease progresses, or a patient dies from any cause. Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.
Inavolisib is an investigational, oral targeted treatment with best-in-class potential that could provide well-tolerated, durable disease control and potentially improved outcomes for people with hormone receptor (HR)-positive, PIK3CA-mutated breast cancer, a common yet often overlooked mutation found in approximately 40% of this population.1 Inavolisib has been designed to help minimise the overall toxicity of treatment and is differentiated from other PI3K inhibitors due to its high in vitro potency and specificity for the PI3K alpha (PI3Kα) isoform inhibition, together with its unique mechanism of action, that leads to specific degradation of mutant PI3K alpha.3,4 Inavolisib is currently being investigated in three Roche-sponsored Phase III clinical studies in PIK3CA-mutated locally advanced or metastatic breast cancer: Hormone receptor (HR)-positive breast cancer is the most prevalent type of all breast cancers.8 A defining feature of HR-positive breast cancer is that its tumour cells have receptors that attach to one or both hormones – estrogen or progesterone – which can contribute to tumour growth.9 People diagnosed with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options.10-12 The PI3K signalling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism for resistance to endocrine therapy and CDK4/6 inhibitors.13 Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. For more information, please visit www.roche.com.
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[2] He Y, et al. Targeting PI3K/Akt signal transduction for cancer therapy. Signals Transduction and Targeted Therapy. 2021; 6: 425 [4] Hong R., et al. GDC-0077 is a selective PI3K alpha inhibitorPI3K alpha inhibitor that demonstrates robust efficacy in PIK3CA mutant breast cancer models as a single agent and in combination with standard of care therapies. Cancer Res. 2018;78(4):4-14. https://doi-org.libproxy1.nus.edu.sg/10.1158/1538-7445.SABCS17-PD4-14 [6] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy (INAVO121) [Internet; cited 2023 December] Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05646862 [8] National Cancer Institute: Surveillance, Epidemiology and Ends Result Program. Cancer Stat Facts: Female Breast Cancer Subtypes. [Internet; cited 2023 December] Available from: https://seer.cancer.gov/statfacts/html/breast-subtypes.html [10] Galipeau N., et al. Understanding key symptoms, side effects, and impacts of HR+/HER- advanced breast cancer: qualitative study findings. J Patient-Rep Outcomes. 2019;3(1):10. doi: 10.1186/s41687-019-0098-1 [11] Buonomoa B. and Peccatori FA. Fertility preservation in endocrine responsive breast cancer: data and prejudices. ecancer. 2020;14:1157. doi: 10.3332/ecancer.2020.1157 [13] Schwartzberg LS. and Vidal GA. Targeting PIK3CA Alterations in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2 Negative Advanced Breast Cancer: New Therapeutic Approaches and Practical Considerations. Clin Breast Cancer. 2020;20(4):e439-e449. doi: 10.1016/j.clbc.2020.02.002 Roche Global Media Relations Phone: +41 61 688 8888 / e-mail: media.relations@roche.com
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Investor Relations North America
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05122023_MR_Phase III results for inavolisib_en