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The Itovebi (inavolisib)-based regimen reduced the risk of death by more than 30% in people with PIK3CA-mutated HR-positive, HER2-negative advanced breast cancer, compared with palbociclib and fulvestrant alone –
– The PIK3CA mutation is found in approximately 40% of HR-positive advanced breast cancers and is associated with a poor prognosis –
– New data are being presented in an oral session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the New England Journal of Medicine –
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today positive final results from the overall survival (OS) analysis of the Phase III INAVO120 study. These data showed Itovebi TM (inavolisib), in combination with palbociclib (Ibrance ® ) and fulvestrant, reduced the risk of death by more than 30% compared with palbociclib and fulvestrant alone. This represents a statistically significant and clinically meaningful improvement in overall survival for people with PIK3CA -mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, endocrine-resistant, locally advanced or metastatic breast cancer. The results are being presented in an oral session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the New England Journal of Medicine (NEJM).
"For the first time, a PI3K pathway-targeted drug has shown it can help people with this breast cancer subtype live longer," said Levi Garraway, M.D., Ph.D., Genentech's chief medical officer and head of Global Product Development. "Itovebi exemplifies our continued commitment to improve survival rates for people with this common PIK3CA mutation, for whom more effective treatment options are needed."
"The landmark data for the inavolisib-based regimen showed not only a doubling in progression-free survival, but importantly that it extended lives and gave people more time without chemotherapy," said Professor Nicholas Turner, lead study author and professor of molecular oncology at The Institute of Cancer Research, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, London, United Kingdom. "These results give us confidence that this regimen could become the new standard of care in the first-line setting, having demonstrated a substantial benefit on patient outcomes and quality of life."
The Itovebi-based regimen demonstrated a meaningful OS benefit compared with palbociclib and fulvestrant alone. The median OS was 34.0 months (95% CI: 28.4–44.8) for people in the Itovebi arm, compared with 27.0 months (95% CI: 22.8–38.7) in the palbociclib and fulvestrant arm (stratified hazard ratio [HR]=0.67; 95% CI: 0.48–0.94, p-value=0.0190 [boundary=0.0469]). The benefit seen in delaying cancer progression was maintained in the updated analysis, with the Itovebi-based regimen showing a consistent improvement in median progression free survival of 17.2 months versus 7.3 months (stratified HR=0.42, 95% CI: 0.32-0.55) in the comparator arm.
The Itovebi-based regimen also led to a statistically significant improvement in objective response rate (the percentage of patients whose signs of cancer completely disappear or their tumors shrink significantly after treatment) and ad-hoc exploratory analyses showed it substantially delayed time to chemotherapy by approximately two years (stratified HR=0.43; 95% CI: 0.30-0.60). No new safety signals were observed at the time of the final OS analysis, with a low discontinuation due to adverse events supporting good tolerability.
Beyond INAVO120, Itovebi is currently being investigated in three company-sponsored Phase III studies (INAVO121, INAVO122, INAVO123), all in PIK3CA -mutated, locally advanced or metastatic breast cancer in various combinations. We are exploring additional studies in breast cancer and other tumor types with the hope of providing the benefit of this targeted therapy to more people with PIK3CA mutations.
About the INAVO120 study
The INAVO120 study [ NCT04191499 ] is a Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of Itovebi™ (inavolisib) in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA -mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.
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 randomization 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.
Beyond INAVO120, Itovebi is currently being investigated in three additional company-sponsored Phase III clinical studies in PIK3CA -mutated locally advanced or metastatic breast cancer in various combinations:
- in combination with fulvestrant versus alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer post cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and endocrine combination therapy (INAVO121; NCT05646862).
- in combination with dual HER2 blockade versus dual HER2 blockade and optional physician's choice of endocrine therapy as a maintenance treatment in HER2-positive disease (INAVO122; NCT05894239).
- in combination with CDK4/6i and letrozole versus placebo plus a CDK4/6i and letrozole in the first-line setting in endocrine-sensitive, PIK3CA -mutated HR-positive/HER2-negative breast cancer (INAVO123; NCT06790693).
About hormone receptor (HR)-positive breast cancer
HR-positive breast cancer is the most prevalent type of all breast cancers, accounting for approximately 70% of cases. A defining feature of HR-positive breast cancer is that its tumor cells have receptors that attach to one or both hormones – estrogen or progesterone – which can contribute to tumor growth. 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. The PI3K signaling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors.
What is Itovebi?
Itovebi (inavolisib) is a prescription medicine used in combination with the medicines palbociclib and fulvestrant to treat adults who have hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has an abnormal phosphatidylinositol-3-kinase catalytic subunit alpha ( PIK3CA ) gene, and has spread to nearby tissue or lymph nodes (locally advanced), or to other parts of the body (metastatic), and has come back after hormone (endocrine) therapy.
Your healthcare provider will test your cancer for abnormal PIK3CA genes to make sure that Itovebi is right for you.
It is not known if Itovebi is safe and effective in children.
Important Safety Information
What are the possible side effects of Itovebi?
Itovebi may cause serious side effects, including:
- High blood sugar levels (hyperglycemia). High blood sugar is common with Itovebi and may be severe. Your healthcare provider will monitor your blood sugar levels before you start and during treatment with Itovebi. Your blood sugar levels may be monitored more often if you have a history of Type 2 diabetes. Your healthcare provider may also ask you to self-monitor and report your blood sugar levels at home. This will be required more frequently in the first 4 weeks of treatment. If you are not sure how to test your blood sugar levels, talk to your healthcare provider. You should stay well-hydrated during treatment with Itovebi. Tell your healthcare provider right away if you develop symptoms of high blood sugar, including:
- difficulty breathing
- nausea and vomiting (lasting more than 2 hours)
- stomach pain
- excessive thirst
- dry mouth
- more frequent urination than usual or a higher amount of urine than normal
- blurred vision
- unusually increased appetite
- weight loss
- fruity-smelling breath
- flushed face and dry skin
- feeling unusually sleepy or tired
- confusion
- Mouth sores (stomatitis). Mouth sores are common with Itovebi and may be severe. Tell your healthcare provider if you develop any of the following in your mouth:
- pain
- swelling
- redness
- ulcers
- Diarrhea is common with Itovebi and may be severe. Severe diarrhea can lead to the loss of too much body water (dehydration) and kidney injury. Tell your healthcare provider right away if you develop diarrhea, stomach-area (abdominal) pain, or see mucus or blood in your stool during treatment with Itovebi. Your healthcare provider may tell you to drink more fluids or take medicines to treat your diarrhea.
Your healthcare provider may tell you to decrease your dose, temporarily stop your treatment, or completely stop your treatment with Itovebi if you develop certain serious side effects.
The most common side effects and abnormal blood test results of Itovebi when used in combination with palbociclib and fulvestrant include:
- decreased white blood cell counts, red blood cell counts, and platelet counts
- decreased blood levels of calcium, potassium, sodium, and magnesium
- increased creatinine blood levels
- tiredness
- increased blood levels of the liver enzyme alanine transaminase (ALT)
- nausea
- rash
- loss of appetite
- COVID-19 infection
- headache
Itovebi may affect fertility in males and in females who are able to become pregnant. Talk to your healthcare provider if this is a concern for you.
These are not all the possible side effects of Itovebi. Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch . You may also report side effects to Genentech at (877) 436-3683.
Before you take Itovebi, tell your healthcare provider about all of your medical conditions, including if you:
- have a history of diabetes or high blood sugar
- have kidney problems
- are pregnant or plan to become pregnant. Itovebi can harm your unborn baby.
Females who are able to become pregnant:
- Your healthcare provider will check to see if you are pregnant before you start treatment with Itovebi.
- You should use effective non-hormonal birth control (contraception) during treatment with Itovebi and for 1 week after your last dose. Talk to your healthcare provider about what birth control method is right for you during this time.
- Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Itovebi.
Males with female partners who are able to become pregnant:
- You should use effective birth control (contraception) during treatment with Itovebi and for 1 week after your last dose.
- are breastfeeding or plan to breastfeed. It is not known if Itovebi passes into your breastmilk. Do not breastfeed during treatment with Itovebi and for 1 week after your last dose. Talk to your healthcare provider about the best way to feed your baby during treatment with Itovebi.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Please see additional Important Safety Information in the full Itovebi Prescribing Information or visit https://www.itovebi.com .
About Genentech in Breast Cancer
Genentech has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough outcomes in human epidermal growth factor 2-positive and triple-negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including estrogen receptor-positive breast cancer, which is a form of hormone receptor-positive breast cancer, the most prevalent type of all breast cancers.
About Genentech
Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com .
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