Drugs Trials Snapshot: ITOVEBI
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the ITOVEBI Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
ITOVEBI (inavolisib)
eye-TOVE-bee
Genentech, Inc.
Original Approval date: October 10, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ITOVEBI is a medicine approved for use along with palbociclib and fulvestrant to treat hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that also has a change (known as a mutation) in a gene called PIK3CA.
How is this drug used?
ITOVEBI is a tablet that is taken by mouth once a day.
Who participated in the clinical trials?
The FDA approved ITOVEBI in combination with palbociclib and fulvestrant, based on the results from a clinical trial (INAVO120/NCT04191499) that enrolled 325 study participants with PIK3CA-mutated, HR+/HER2– advanced or metastatic breast cancer whose cancer worsened during or within one year of finishing a previous hormone therapy. The trial was conducted at 171 sites in 28 countries in Asia, Australia, Europe, South America, and North America; 16 study participants were from trial sites in the United States.
How were the trials designed?
ITOVEBI was studied in a clinical trial that enrolled people with PIK3CA-mutated, HR+, HER2– advanced or metastatic breast cancer. The eligible participants were randomly assigned to receive either ITOVEBI with palbociclib and fulvestrant or placebo with palbociclib and fulvestrant.
Study participants were able to continue study treatment until their disease worsened or the treatment became too toxic. The benefit of ITOVEBI was assessed by measuring the difference in how long it took until participants’ cancer got worse between those who received ITOVEBI and those who received placebo.
How were the trials designed?
ITOVEBI was evaluated in INAVO120, a randomized, placebo-controlled, global trial of study participants with locally advanced or metastatic HR-positive, HER2-negative breast cancer following recurrence or progression on or after adjuvant endocrine therapy. People were screened to check if they were able to participate in the study. Importantly, their cancer needed to show the presence of one or more PIK3CA mutations in blood samples or a tumor biopsy. Tests were also done to ensure people did not have underlying conditions like diabetes or high HbA1C levels that might cause additional toxicity.
Of the 325 participants enrolled, 161 received ITOVEBI in combination with palbociclib and fulvestrant and 164 received placebo in combination with palbociclib and fulvestrant.
The main result measured in the study was whether ITOVEBI had worked to extend the time participants lived without their cancer getting worse (investigator-assessed progression free survival).
Other key results from this study included:
- How long people lived, even after they stopped using the study treatment (overall survival)
- How many participants had a tumor size reduction of a predefined amount of their cancer and for a minimum time period after treatment (objective response rate)
- The number and seriousness of unwanted side effects
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the efficacy of ITOVEBI.
Figure 1. Baseline Demographics by Sex, Efficacy Population
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the clinical trial used to evaluate the efficacy of ITOVEBI.
Figure 2. Baseline Demographics by Race, Efficacy Population
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the efficacy of ITOVEBI.
Figure 3. Baseline Demographics by Age, Efficacy Population
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the clinical trial used to evaluate the efficacy of ITOVEBI.
Figure 4. Baseline Demographics by Ethnicity, Efficacy Population
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics
| Demographic | ITOVEBI N=161 |
Placebo N=164 |
All N=325 |
|---|---|---|---|
| Age, years | |||
| Median | 53.0 | 54.5 | 54.0 |
| Min, max | 27, 77 | 29, 79 | 27, 79 |
| Age group, years, n (%) | |||
| <65 | 136 (84.5) | 130 (79.3) | 266 (81.8) |
| ≥65 | 25 (15.5) | 34 (20.7) | 59 (18.2) |
| Sex, n (%) | |||
| Female | 156 (96.9) | 163 (99.4) | 319 (98.2) |
| Male | 5 (3.1) | 1 (0.6) | 6 (1.8) |
| Race, n (%) | |||
| Asian | 61 (37.9) | 63 (38.4) | 124 (38.2) |
| Black or African American | 1 (0.6) | 1 (0.6) | 2 (0.6) |
| White | 94 (58.4) | 97 (59.1) | 191 (58.8) |
| Unknown | 5 (3.1) | 3 (1.8) | 8 (2.5) |
| Ethnicity, n (%) | |||
| Hispanic or Latino | 10 (6.2) | 10 (6.1) | 20 (6.2) |
| Not Hispanic or Latino | 145 (90.1) | 149 (90.9) | 294 (90.5) |
| Unknown or Not reported | 6 (3.7) | 5 (3.0) | 11 (3.4) |
Source: Adapted from FDA Review
What are the benefits of this drug?
The time participants lived without their cancer worsening more than doubled for those who received ITOVEBI than those in the placebo group: they had a median time to disease worsening of 15.0 months compared to 7.3 months for participants in the placebo group.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Efficacy Results, Efficacy Population
| Progression-Free Survivala,b | ITOVEBI N=161 |
Placebo N=164 |
|---|---|---|
| Patients with event, n (%) | 82 (51) | 113 (69) |
| Median, months (95% CI) | 15.0 (11.3, 20.5) | 7.3 (5.6, 9.3) |
| Hazard ratio (95% CI) | 0.43 (0.32, 0.59) |
|
| p-value | < 0.0001 |
|
Source: Adapted from ITOVEBI Prescribing Information
a Per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
b Based on investigator assessment
Abbreviations: CI, confidence interval
At the time of the progression free survival analysis, overall survival data were not mature with 30% deaths in the overall population.
Were there any differences in how well the drug worked in clinical trials among sex, race, age, and ethnicity?
- Sex: As breast cancer is rare in males, ITOVEBI was only tested in a few male patients in INAVO120, and therefore there is not enough data to suggest that the benefit of ITOVEBI did or did not differ by sex. There was no known biological rationale for a differential effect of ITOVEBI based on sex.
- Race: The majority of participants in the clinical trial were White or Asian. ITOVEBI worked similarly well in White and Asian participants. The number of participants of other races was limited; therefore, it could not be accurately determined whether there are differences in how ITOVEBI worked among other races.
- Age: The study did not include a sufficient number of participants at 65 years of age and over; therefore, differences in how ITOVEBI worked among participants younger and older than 65 years of age could not be determined.
- Ethnicity: The study did not include a sufficient number of Hispanic or Latino participants; therefore, differences in how ITOVEBI worked among not Hispanic or Latino participants and Hispanic or Latino participants could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Progression-Free Survival (Investigator-Assessed) by Subgroup, Efficacy Population
| Subgroup | N | ITOVEBI | Placebo | Hazard Ratioa | 95% Wald CIa | ||
|---|---|---|---|---|---|---|---|
| n | Median (Months) | n | Median (Months) | ||||
| Age, years | |||||||
| <65 | 266 | 136 | 16.6 | 130 | 7.2 | 0.44 | (0.32, 0.60) |
| ≥65 | 59 | 25 | 9.3 | 34 | 10.7 | 0.96 | (0.50, 1.83) |
| Sex | |||||||
| Female | 319 | 156 | 14.6 | 163 | 7.3 | 0.51 | (0.38, 0.68) |
| Male | 6 | 5 | 24.2 | 1 | NE | NE | NE |
| Race | |||||||
| Asian | 124 | 61 | 18.2 | 63 | 5.8 | 0.43 | (0.27, 0.69) |
| Black or African American | 2 | 1 | 9.0 | 1 | 6.8 | NE | NE |
| White | 191 | 94 | 16.6 | 97 | 7.5 | 0.54 | (0.38, 0.79) |
| Unknown | 8 | 5 | 11.0 | 3 | 7.2 | 0.59 | (0.08, 4.25) |
| Ethnicity | |||||||
| Hispanic or Latino | 20 | 10 | 24.2 | 10 | 20.3 | 0.58 | (0.11, 3.00) |
| Not Hispanic or Latino | 294 | 145 | 15.0 | 149 | 7.3 | 0.47 | (0.35, 0.63) |
| Not reported | 5 | 2 | 9.0 | 3 | 7.2 | 0.57 | (0.05, 6.33) |
| Unknown | 6 | 4 | 6.8 | 2 | 1.6 | 1.16 | (0.12, 11.39) |
Source: Adapted from FDA Review
a Unstratified analysis
Abbreviations: CI, confidence interval; NE, not evaluable
What are the possible side effects?
ITOVEBI carries Warnings and Precautions for high blood sugar, mouth sores, and diarrhea. The most common side effects of ITOVEBI, when used in combination with palbociclib and fulvestrant, include high blood sugar levels (hyperglycemia), mouth sores (stomatitis), diarrhea, fatigue, nausea, and rash.
What are the possible side effects (results of trials used to assess safety)?
The possible side effects occurring in ≥10% of participants treated with ITOVEBI and ≥5% (all grades) or ≥2% (grade 3 to 4) more frequently than in participants treated with placebo are shown in Table 4.
Laboratory abnormalities occurring in ≥30% of participants treated with ITOVEBI and ≥2% (all grades or grade 3 to 4) more frequently than participants treated with placebo are shown in Table 5.
Table 4. Adverse Reactions ≥10% With ≥5% (All Grades) or ≥2% (Grade 3 to 4) Higher Incidence in the ITOVEBI Arm in INAVO120, Safety Population
| Adverse Reaction | ITOVEBI, N=162 |
Placebo, N=162 |
||
|---|---|---|---|---|
| All Grades % |
Grade 3 to 4 % |
All Grades % |
Grade 3 to 4 % |
|
| Gastrointestinal disorders | ||||
| Stomatitis1 | 51 | 6* | 27 | 0 |
| Diarrhea | 48 | 3.7* | 16 | 0 |
| Nausea | 28 | 0.6* | 17 | 0 |
| Vomiting | 15 | 0.6* | 5 | 1.2* |
| General disorders and administration site conditions | ||||
| Fatigue | 38 | 1.9* | 25 | 1.2* |
| Skin and subcutaneous tissue disorders | ||||
| Rashb | 26 | 0 | 19 | 0 |
| Alopecia | 19 | 0 | 6 | 0 |
| Dry skin1 | 13 | 0 | 4.3 | 0 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 24 | 0 | 9 | 0 |
| Infections and infestations | ||||
| COVID-19 infection | 23 | 1.9 | 10 | 0.6 |
| Urinary tract infection1 | 15 | 1.2* | 9 | 0 |
| Nervous system disorders | ||||
| Headache1 | 22 | 0 | 14 | 0 |
| Investigations | ||||
| Decreased weight | 17 | 3.7* | 0.6 | 0 |
Source: Adapted from ITOVEBI Prescribing Information
1 Represents a composite of multiple related terms
* No Grade 4 adverse reactions were observed.
Table 5. Select Laboratory Abnormalities ≥30% With a ≥2% (All Grades or Grade 3 to 4) Higher Incidence in the ITOVEBI Arm in INAVO120, Safety Population
| Laboratory Abnormality | ITOVEBIa |
Placebob |
||
|---|---|---|---|---|
| All Grades % |
Grade 3 to 4 % |
All Grades % |
Grade 3 to 4 % |
|
| Hematology | ||||
| Neutrophils (total, absolute) decreased | 95 | 82 | 97 | 79 |
| Hemoglobin decreased | 88 | 8* | 85 | 2.5* |
| Platelets decreased | 84 | 16 | 71 | 3.7 |
| Lymphocytes (absolute) decreased | 72 | 9 | 68 | 14 |
| Chemistry | ||||
| Glucose (fasting) increased | 85 | 12 | 43 | 0 |
| Calcium decreased | 42 | 3.1 | 32 | 3.7 |
| Potassium decreased | 38 | 6 | 21 | 0.6* |
| Creatinine increased | 38 | 1.9* | 30 | 1.2* |
| ALT increased | 34 | 3.1* | 29 | 1.2* |
| Sodium decreased | 28 | 2.5* | 19 | 2.5 |
| Magnesium decreased | 27 | 0.6 | 21 | 0 |
| Lipase (fasting) increased | 16 | 1.4* | 7 | 0 |
Source: Adapted from ITOVEBI Prescribing Information
* No Grade 4 laboratory abnormalities were observed.
a The denominator used to calculate the rate varied from 122 to 160 based on the number of participants with a baseline value and at least one post-treatment value.
b The denominator used to calculate the rate varied from 131 to 161 based on the number of participants with a baseline value and at least one post-treatment value.
Abbreviations: ALT, alanine aminotransferase
Were there any differences in side effects among sex, race, and age?
- Sex: Consistent with the disease demographics for breast cancer, the vast majority of participants were female and there were not enough male participants to determine whether there were any differences in side effects between sexes.
- Race: The majority of participants were White or Asian. White participants treated with ITOVEBI appeared to experience more diarrhea in comparison to Asian participants (52.1% versus 43.5%). The number of participants of other races was limited; therefore, it could not be accurately determined whether there were any differences in side effects among other races.
- Age: The majority of participants enrolled in the trial were younger than 65 years old with only a small number of participants that were ≥65 years old. There were not enough participants that were ≥65 years old to determine whether there were any differences in side effects between the age groups. It was noted that dosage modifications or interruptions of ITOVEBI due to adverse reactions occurred at a higher incidence for patients ≥65 years of age compared to younger patients (79% versus 68%, respectively).
- Ethnicity: The majority of the participants were not Hispanic or Latino, and there were not enough Hispanic or Latino participants to determine whether there were any differences in side effects between the ethnic groups.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 6. Overview of Adverse Events by Demographic Subgroup, Safety Population
| Subgroup | ITOVEBI N=162 n/Ns (%) |
Placebo N=162 n/Ns (%) |
|---|---|---|
| Sex | ||
| Female | 155/157 (98.7) | 161/161 (100) |
| Male | 5/5 (100) | 1/1 (100) |
| Age group, years | ||
| <65 | 136/138 (98.6) | 128/128 (100) |
| ≥65 | 24/24 (100) | 34/34 (100) |
| Age group ≥75, years | ||
| ≥75 | 4/4 (100) | 6/6 (100) |
| Race | ||
| Asian | 62/62 (100) | 62/62 (100) |
| Black or African American | 1/1 (100) | 1/1 (100) |
| Unknown | 5/5 (100) | 3/3 (100) |
| White | 92/94 (97.9) | 96/96 (100) |
| Ethnicity | ||
| Hispanic or Latino | 10/11 (90.9) | 9/9 (100) |
| Not Hispanic or Latino | 144/145 (99.3) | 148/148 (100) |
| Not reported | 2/2 (100) | 3/3 (100) |
| Unknown | 4/4 (100) | 2/2 (100) |
Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.
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