Genentech’s Itovebi Extends Survival in HR-Positive Advanced Breast Cancer, New Data Reveal

– 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 –

SOUTH SAN FRANCISCO, Calif. – Genentech, a member of the Roche Group, today unveiled encouraging late-stage results from the overall survival (OS) analysis of its Phase III INAVO120 study. The data showcase that Itovebi (inavolisib), when used in combination with palbociclib (Ibrance) and fulvestrant, outperformed the standard palbociclib and fulvestrant regimen, showing a reduction in the risk of death by over 30%. This outcome signifies a statistically significant and clinically relevant stride in improving overall survival for patients battling PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, endocrine-resistant, locally advanced or metastatic breast cancer. The full findings are slated for presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneous publication in the prestigious 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 treatment demonstrated a pronounced OS benefit when compared with the palbociclib and fulvestrant combination. The median OS was 34.0 months for patients on the Itovebi arm, versus 27.0 months in the control arm (stratified hazard ratio [HR]=0.67; 95% CI: 0.48–0.94, p-value=0.0190 [boundary=0.0469]). This advantage in delaying cancer progression was sustained in the updated analysis, with the Itovebi regimen exhibiting a consistent improvement in median progression-free survival of 17.2 months against 7.3 months in the comparator group (stratified HR=0.42, 95% CI: 0.32-0.55).

Further bolstering the positive outcomes, the Itovebi-based regimen also led to a statistically significant boost in the objective response rate (the proportion of patients showing complete disappearance of cancer signs or significant tumor shrinkage). Moreover, exploratory analyses indicated a substantial delay in the need for chemotherapy, extending the timeframe by roughly two years (stratified HR=0.43; 95% CI: 0.30-0.60). Importantly, no fresh safety signals were reported in the final OS analysis, and a low rate of treatment discontinuation due to adverse events suggests a good tolerability profile.

Beyond the INAVO120 trial, Itovebi is currently under evaluation in three Genentech-sponsored Phase III studies (INAVO121, INAVO122, INAVO123), all targeting PIK3CA-mutated, locally advanced or metastatic breast cancer in various combination therapies. The company is also exploring additional studies across breast cancer and other tumor types, with the aim of expanding the benefits of this targeted therapy to a broader patient population 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 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 enrolled 325 patients, randomly assigned to receive either the investigational or control arm. The primary benchmark was progression-free survival, assessed by investigators, defined as the time from the point of randomization in the clinical trial until the time the disease progresses, or a patient passes away from any cause. Secondary endpoints encompassed overall survival, objective response rate, and clinical benefit rate.

Building on these initial findings, Itovebi is also being studied in three further company-sponsored Phase III clinical studies focused on PIK3CA-mutated locally advanced or metastatic breast cancer, in diverse 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).

Understanding Hormone Receptor (HR)-Positive Breast Cancer

HR-positive breast cancer stands as the predominant type across all breast cancer diagnoses, accounting for around 70% of cases. A defining trait of this subtype is the presence of tumor cell receptors that bind to either or both of the hormones – estrogen and progesterone – potentially fueling tumor growth. Patients diagnosed with HR-positive metastatic breast cancer frequently contend with the risk of disease progression and treatment-related side effects, underscoring the critical need for additional treatment choices. Dysregulation of the PI3K signaling pathway is a common theme in HR-positive breast cancer, often triggered by activating PIK3CA mutations which have emerged as a mechanism potentially responsible for endocrine therapy resistance alongside cyclin-dependent kinase 4/6 inhibitors.

What is Itovebi?

Itovebi (inavolisib) is a medication available by prescription, designed to be used in combination with palbociclib and fulvestrant. It is indicated for adults with 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. The cancer must have spread locally (to nearby tissue or lymph nodes) or metastasized to other parts of the body and returned following prior hormonal therapy.

Your healthcare provider will conduct testing of your cancer to verify the presence of abnormal PIK3CA genes before prescribing Itovebi.

The safety and efficacy of Itovebi in children have not been established.

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

For over three decades, Genentech has spearheaded significant advancements in breast cancer research. Its mission revolves around assisting as many individuals afflicted by the disease as possible. Their range of medicines, accompanied by companion diagnostic tools, have facilitated groundbreaking achievements in the realm of human epidermal growth factor 2-positive and triple-negative breast cancers. As our comprehension of breast cancer biology rapidly accelerates, Genentech is actively working to discover new biomarkers and treatment avenues for other subtypes of the disease, including estrogen receptor-positive breast cancer, a form of hormone receptor-positive breast cancer, which represents 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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Source: Genentech