FDA Approves Genentech’s Itovebi, a Targeted Treatment for Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer With a PIK3CA Mutation
– Approval is based on Phase III INAVO120 results, showing the ItovebiTM (inavolisib)-based regimen more than doubled progression-free survival compared with palbociclib and fulvestrant alone in the first-line setting –
– This approval helps address an urgent unmet need in breast cancer for people with a PIK3CA mutation, one of the most commonly mutated genes in HR-positive disease, associated with poor prognosis –
– Itovebi is Genentech’s first targeted therapy approved for people with HR-positive disease, the most prevalent breast cancer subtype, marking an important step in our ambition to continue bringing innovative medicines to more people with breast cancer –
“The PI3K pathway plays a pivotal role in disease progression and has been challenging to target,” said
“With the approval of this Itovebi-based regimen, we continue our long-standing track record of cancer therapeutic discovery by offering an important new first-line option for people living with HR-positive breast cancer with a PIK3CA mutation,” said
This approval is based on results of the pivotal Phase III INAVO120 study, which showed that the Itovebi-based regimen reduced the risk of disease worsening or death by 57% compared with 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) in the first-line setting, demonstrating a statistically significant and clinically meaningful benefit. Overall survival (OS) data were immature at the time of primary analysis, but a clear positive trend was observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338 [boundary of 0.0098]). Follow-up for OS is continuing to the next analysis.
“We are thrilled by the approval of the Itovebi-based regimen, which is a huge step forward for advanced breast cancer patients with a PIK3CA mutation,” said
The Itovebi-based regimen was granted FDA Priority Review and Breakthrough Therapy Designation in
Itovebi is currently being investigated in various combinations across three company-sponsored Phase III clinical studies (INAVO120, INAVO121, INAVO122) in PIK3CA-mutated locally advanced or metastatic breast cancer. We continue to evaluate opportunities to expand our clinical development program to address patient unmet needs in various tumor types across oncology.
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 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
- 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
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 .
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