– Itovebi^TM (inavolisib)-based regimen demonstrated a statistically significant and clinically meaningful benefit, reducing the risk of disease worsening or death by 57% compared with palbociclib and fulvestrant alone in the INAVO120 study –

– The U.S. FDA recently approved the Itovebi-based regimen as a first-line treatment for people with HR-positive, HER2-negative breast cancer with a PIK3CA mutation, one of the most commonly mutated genes in HR-positive disease –

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that a detailed analysis of the positive Phase III INAVO120 results, evaluating Itovebi^TM (inavolisib) in combination with palbociclib (Ibrance^®) and fulvestrant was published in the New England Journal of Medicine. The U.S. Food and Drug Administration (FDA) recently approved Itovebi in combination with palbociclib and fulvestrant, for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. Data from INAVO120 are also being used for filing submissions to other global health authorities, including the European Medicines Agency.

“With a doubling of progression-free survival and consistent benefits in people whose disease had spread to multiple challenging-to-treat locations, including the liver and lungs, these INAVO120 data are significant for patients,” said Komal Jhaveri, M.D., section head for the endocrine therapy research portfolio and clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center and one of the principal investigators of the INAVO120 study. “I’m confident this Itovebi-based regimen could become a new first-line standard of care for this patient population with one of the most commonly mutated genes in metastatic breast cancer, associated with a poor prognosis.”

Results showed the Itovebi-based regimen reduced the risk of disease worsening or death (progression-free survival [PFS]) by 57% compared to palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p<0.0001). PFS benefit was consistent across all pre-specified subgroups, including people whose disease had spread to three or more locations, which is characterized as difficult-to-treat disease. Overall survival (OS) data were immature at the time of analysis, but a clear positive trend has been observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338 [boundary of 0.0098]). Follow-up for OS will continue to the next analysis.

“Publication of these Phase III results in the New England Journal of Medicine further highlights the transformative potential of the Itovebi-based regimen,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “This new treatment exemplifies our ambition to target specific disease pathways more effectively and improve outcomes in people with breast cancer, while also emphasizing the importance of comprehensive testing for mutations like PIK3CA at the time of diagnosis.”

The PIK3CA mutation is found in approximately 40% of HR-positive metastatic breast cancers and is associated with a poor prognosis. Historically, the use of PI3K targeted therapy in the first-line advanced setting has been limited and therefore testing for PIK3CA mutations is not common at the time of diagnosis. Early biomarker testing with an FDA-approved test, such as Foundation Medicine’s FoundationOne^®Liquid CDx, before first-line treatment is crucial to help identify people who may benefit from targeted therapy, such as Itovebi.

Itovebi is currently being investigated in three company-sponsored Phase III clinical studies (INAVO120, INAVO121, INAVO122) 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 bringing the benefit of this targeted therapy to more people with PIK3CA mutations and addressing patient unmet needs.

About the INAVO120 study

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 two 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 inhibitor and endocrine combination therapy (INAVO121; NCT05646862), and
• 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).

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
  • blurred vision
  • nausea and vomiting (lasting more than 2 hours)
  • unusually increased appetite
  • stomach pain
  • weight loss
  • excessive thirst
  • fruity-smelling breath
  • dry mouth
  • flushed face and dry skin
  • more frequent urination than usual or a higher amount of urine than normal
  • 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. 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 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 and for 1 week after your last dose of Itovebi. 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 HER2-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.

Dr. Jhaveri has financial interests related to Roche and Genentech.

All trademarks used or mentioned in this release are protected by law.

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