TriangleNCT04191499 · CITED IN SOURCE DOCUMENTS
A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2, PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-06-15
This study will evaluate the efficacy, safety, and pharmacokinetics of inavolisib in combination with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in participants with PIK3CA-mutant, hormone receptor (HR)-positive, 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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-Free Survival (PFS)
Percentage of Participants With Objective Response Rate (ORR)
Percentage of Participants With Best Overall Response Rate (BOR)
Duration of Response (DOR)
Percentage of Participants With Clinical Benefit Rate (CBR)
Overall Survival (OS)
Time to Deterioration (TTD) in Pain
TTD in Physical Function (PF)
TTD in Role Function (RF)
TTD in Global Health Status (GHS)
Number of Participants With Adverse Events (AEs)
Plasma Concentration of Inavolisib
Plasma Concentration of Palbociclib
Plasma Concentration of Fulvestrant
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria * Confirmed diagnosis of HR+/HER2- breast cancer * Metastatic or locally advanced disease not amenable to curative therapy * Progression of disease during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen * Receiving LHRH agonist therapy for at least 2 weeks prior to Day 1 of Cycle 1 if pre/peri-menopausal * Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test) * Consent to provide fresh or archival tumor tissue specimen * Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); evaluable "bone-only" disease is not eligible; "bone-only" disease with at least one measurable, soft-tissue component, even if considered disease that is limited to bone but has lytic or mixed lytic/blastic lesions and at least one measurable soft-tissue component per RECIST v1.1 may be eligible * Eastern Cooperative Oncology Group Performance Status of 0 or 1 * Life expectancy of \> 6 months * Adequate hematologic and organ function within 14 days prior to initiation of study treatment Exclusion Criteria * Metaplastic breast cancer * Any history of leptomeningeal disease or carcinomatous meningitis * Any prior systemic therapy for metastatic breast cancer * Prior treatment with fulvestrant or any selective estrogen-receptor degrader, with the exception of participants that have received fulvestrant or any selective estrogen-receptor degrader as part of neoadjuvant therapy only and with treatment duration of no longer than 6 months * Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway * Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes * Known and untreated, or active CNS metastases. Patients with a history of treated CNS metastases may be eligible * Active inflammatory or infectious conditions in either eye, or any eye conditions expected to require surgery during the study treatment period * Symptomatic active lung disease, or requiring daily supplemental oxygen * History of inflammatory bowel disease or active bowel inflammation * Anti-cancer therapy within 2 weeks before study entry * Investigational drug(s) within 4 weeks before randomization * Prior radiotherapy to \>= 25% of bone marrow, or hematopoietic stem cell or bone marrow transplantation * Chronic corticosteroid therapy or immunosuppressants * Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 2 weeks after the final dose of study treatment * Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants will receive inavolisib, palbociclib, and fulvestrant.
- intervention Names
- Drug: Inavolisib
- Drug: Palbociclib
- Drug: Fulvestrant
- label
- Inavolisib + Palbociclib + Fulvestrant
- type
- EXPERIMENTAL
- description
- Participants will receive placebo, palbociclib, and fulvestrant. Participants randomized to the placebo arm who are still deriving benefit from the study treatment will be given an optional opportunity to crossover to the inavolisib arm.
- intervention Names
- Drug: Placebo
- Drug: Palbociclib
- Drug: Fulvestrant
- label
- Placebo + Palbociclib + Fulvestrant
- type
- PLACEBO_COMPARATOR
- interventions
- arm Group Labels
- Inavolisib + Palbociclib + Fulvestrant
- description
- Participants will receive oral inavolisib on Days 1-28 of each 28-day cycle.
- name
- Inavolisib
- other Names
- GDC-0077
- type
- DRUG
- arm Group Labels
- Placebo + Palbociclib + Fulvestrant
- description
- Participants will receive oral placebo on Days 1-28 of each 28-day cycle.
- name
- Placebo
- type
- DRUG
- arm Group Labels
- Inavolisib + Palbociclib + Fulvestrant
- Placebo + Palbociclib + Fulvestrant
- description
- Participants will receive oral palbociclib on Days 1-21 of each 28-day cycle.
- name
- Palbociclib
- type
- DRUG
- arm Group Labels
- Inavolisib + Palbociclib + Fulvestrant
- Placebo + Palbociclib + Fulvestrant
- description
- Participants will receive intramuscular (IM) fulvestrant approximately every 4 weeks.
- name
- Fulvestrant
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- DOUBLE
- who Masked
- PARTICIPANT
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 325
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 or death from any cause (whichever occurs first). Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression. Data for participants without the occurrence of PD or death as of the clinical cutoff date (CCOD) were censored at the time of the last tumor assessment prior to the CCOD. Median PFS was calculated using the Kaplan-Meier methodology.
- measure
- Progression-Free Survival (PFS)
- time Frame
- Up to 3.7 years
- secondary Outcomes
- description
- ORR is defined as the percentage of participants with a complete response (CR) and/or partial response (PR) on at least two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR is defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline.
- measure
- Percentage of Participants With Objective Response Rate (ORR)
- time Frame
- Up to approximately 6 years
- description
- BOR is defined as the percentage of participants with a CR or PR, as determined by the investigator according to RECIST v1.1. CR is defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline.
- measure
- Percentage of Participants With Best Overall Response Rate (BOR)
- time Frame
- Up to approximately 6 years
- description
- DOR is defined as the time from the first occurrence of a CR or PR to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). CR is defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
- measure
- Duration of Response (DOR)
- time Frame
- Up to approximately 6 years
- description
- CBR is defined as the percentage of participants with a CR, PR, and/or stable disease (SD) for at least 24 weeks, as determined by the investigator according to RECIST v1.1. CR= disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline. PD=at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum in the study.
- measure
- Percentage of Participants With Clinical Benefit Rate (CBR)
- time Frame
- Up to approximately 6 years
- description
- OS is defined as the time from randomization to death from any cause.
- measure
- Overall Survival (OS)
- time Frame
- Up to approximately 6 years
- description
- TTD in pain is defined as the time from randomization to the first documentation of a ≥ 2-point increase from baseline on the "worst pain" item from the Brief Pain Inventory-Short Form (BPI-SF). BPI-SF is a self-administered questionnaire in which the participant was asked to rate severity on a 10-point scale where 0 represents 'No pain/No interference' and 10 represents 'Pain/Interference as bad as you can imagine'. A ≥2-point change is defined as clinically meaningful difference.
- measure
- Time to Deterioration (TTD) in Pain
- time Frame
- From randomization to first documentation of a ≥ 2-point increase (Up to approximately 6 years)
- description
- TTD in physical function is defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline held for two consecutive cycles or initial decrease followed by death or treatment discontinuation within three weeks of last assessment in the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) PF scale (items 1-5). A ≥10-point change is defined as a clinically meaningful difference. EORTC QLQ-C30 is a cancer-specific health-related quality-of life (QoL) questionnaire with 30 questions. For the PF scale, participant responses to 5 questions about daily activities (strenuous activities, long walks, short walks, bed/chair rest \& needing help with eating, dressing, washing themselves, or using the toilet) is scored on a 4-point scale (1=Not at All to 4=Very Much). Scores are linearly transformed on a scale of 0 to 100, with a high score indicating worst functioning.
- measure
- TTD in Physical Function (PF)
- time Frame
- Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years) (Cycle length = 28 days)]
- description
- TTD in Role Function is defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline held for two consecutive cycles, or initial decrease followed by death or treatment discontinuation within three weeks of last assessment in the EORTC QLQ-C30 RF scale (items 6 and 7). A ≥10-point change is defined as clinically meaningful difference. EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. For the role functioning scale, participant responses to the 2 questions "Q6: Were you limited in doing either your work or daily activities" and "Q7: Were you limited in pursuing your hobbies or other leisure time activities" were scored on a 4-point scale (1=Not at All to 4=Very Much). The scores were linearly transformed on a scale of 0 to 100, with a low score indicating better functioning.
- measure
- TTD in Role Function (RF)
- time Frame
- Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years) (Cycle length = 28 days)]
- description
- TTD in (GHS)/health-related quality of life (HRQoL) is defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline held for two consecutive cycles, or initial decrease followed by death or treatment discontinuation within three weeks of last assessment in the EORTC QLQ-30 GHS/HRQoL scale. A ≥10-point change is defined as clinically meaningful difference. EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant responses to the questions regarding Global Health Status (Q29: GHS; "How would you rate your overall health during the past week?") and Quality of Life (Q30: QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better outcome.
- measure
- TTD in Global Health Status (GHS)
- time Frame
- Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years) (Cycle length = 28 days)]
- description
- An AE is an untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.
- measure
- Number of Participants With Adverse Events (AEs)
- time Frame
- Up to approximately 6 years
- measure
- Plasma Concentration of Inavolisib
- time Frame
- Predose on Cycle 1 Days 1, 8 and 15 and Cycle 2 Day 15; 3 hours post-dose on Cycle 1 Days 1 and 15 (Cycle length = 28 days)
- measure
- Plasma Concentration of Palbociclib
- time Frame
- Predose on Cycle 1 Days 1, 8 and 15 and Cycle 2 Day 15; 3 hours post-dose on Cycle 1 Days 1 and 15 (Cycle length = 28 days)
Full study description
- brief Summary
- This study will evaluate the efficacy, safety, and pharmacokinetics of inavolisib in combination with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in participants with PIK3CA-mutant, hormone receptor (HR)-positive, 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.
Source references
- references
- citation
- Jhaveri KL, Im SA, Saura C, Loibl S, Kalinsky K, Schmid P, Loi S, Thanopoulou E, Shankar N, Jin Y, Stout TJ, Clark TD, Song C, Juric D, Turner NC. Overall Survival with Inavolisib in PIK3CA-Mutated Advanced Breast Cancer. N Engl J Med. 2025 Jul 10;393(2):151-161. doi: 10.1056/NEJMoa2501796. Epub 2025 May 31.
- pmid
- 40454641
- type
- DERIVED
- citation
- Turner NC, Im SA, Saura C, Juric D, Loibl S, Kalinsky K, Schmid P, Loi S, Sunpaweravong P, Musolino A, Li H, Zhang Q, Nowecki Z, Leung R, Thanopoulou E, Shankar N, Lei G, Stout TJ, Hutchinson KE, Schutzman JL, Song C, Jhaveri KL. Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. N Engl J Med. 2024 Oct 31;391(17):1584-1596. doi: 10.1056/NEJMoa2404625.
- pmid
- 39476340
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-4e7f28802ca1e65d8cea
- requested nct id
- NCT04191499
- primary nct id
- NCT04191499
- source kind
- fda_spl_label
- source record id
- 7dcc9b87-0aa4-4a00-aced-96be3553e8ac
- source file sha256
- a4bef6778baed183e5bcf581938b0b23d3576dfd9eb6150f2904934a750c5fef
- payload sha256
- ca6091a379b75ec8609c705599f3b8fa40601fe06a578120f237488043d783f9
- payload
- application numbers
- NDA207103
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-4e7f28802ca1e65d8cea
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT04191499
- occurrences
- context exact
- within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for locally advanced or metastatic disease INAVO120 (NCT04191499) was a randomized (1:1), double-blind, placebo-controlled trial evaluating the efficacy of inavolisib in combination with IBRANCE and fulvestrant in adult pati
- end
- 8017
- exact text
- NCT04191499
- start
- 8006
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00400.json
- source file sha256
- a4bef6778baed183e5bcf581938b0b23d3576dfd9eb6150f2904934a750c5fef
- source json pointer
- /results/80/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 7dcc9b87-0aa4-4a00-aced-96be3553e8ac
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 82808ddcf533091fa145ad7d4c5f616daf6170bd40820866aef2a10802917cad
- spl effective time
- 20260702
- spl set id
- e0e6412f-50b4-4fd4-9364-62818d121a07
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-6d0892c0c877d6ee4561
- requested nct id
- NCT04191499
- primary nct id
- NCT04191499
- source kind
- fda_spl_label
- source record id
- 0bf98e9e-7794-47ec-a88f-2fb726c7861a
- source file sha256
- 0dba7a040bbbf460aa9f482c5b67c9f28f75fc9df775ee1e7b345b758f780e07
- payload sha256
- 45c6c675f80ac2b5a2c0623ca82bbb0c6118ecbda317d105174407792cb346a7
- payload
- application numbers
- NDA212436
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-6d0892c0c877d6ee4561
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT04191499
- occurrences
- context exact
- within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for locally advanced or metastatic disease INAVO120 (NCT04191499) was a randomized (1:1), double-blind, placebo-controlled trial evaluating the efficacy of inavolisib in combination with IBRANCE and fulvestrant in adult pati
- end
- 8017
- exact text
- NCT04191499
- start
- 8006
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00000.json
- source file sha256
- 0dba7a040bbbf460aa9f482c5b67c9f28f75fc9df775ee1e7b345b758f780e07
- source json pointer
- /results/34/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 0bf98e9e-7794-47ec-a88f-2fb726c7861a
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 547608d270c79c574ededa9d5486cc8bc3379c3a64b97064eb0de743639a7056
- spl effective time
- 20260702
- spl set id
- fecbdd7d-b729-41b5-9872-231b8fe104ce
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-a88d71ed06dfb6252660
- requested nct id
- NCT04191499
- primary nct id
- NCT04191499
- source kind
- fda_spl_label
- source record id
- 342c459f-fe40-4422-bc31-88d16fbbd4df
- source file sha256
- fc39a8c5cf96bf95ca20b85578140167b66b2741f7d9217f500d9ba0847ac058
- payload sha256
- 183488df1cdd0b0de5d22c541131aa565fd76ed6de7af92b30c971e4101425e4
- payload
- application numbers
- NDA212436
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-a88d71ed06dfb6252660
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT04191499
- occurrences
- context exact
- within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for locally advanced or metastatic disease INAVO120 (NCT04191499) was a randomized (1:1), double-blind, placebo-controlled trial evaluating the efficacy of inavolisib in combination with IBRANCE and fulvestrant in adult pati
- end
- 8017
- exact text
- NCT04191499
- start
- 8006
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00100.json
- source file sha256
- fc39a8c5cf96bf95ca20b85578140167b66b2741f7d9217f500d9ba0847ac058
- source json pointer
- /results/89/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- 342c459f-fe40-4422-bc31-88d16fbbd4df
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 547608d270c79c574ededa9d5486cc8bc3379c3a64b97064eb0de743639a7056
- spl effective time
- 20260706
- spl set id
- 89a142d5-7e61-48bf-9e77-e2cd124c4792
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-d9fd0952be548a47aaff
- requested nct id
- NCT04191499
- primary nct id
- NCT04191499
- source kind
- fda_spl_label
- source record id
- dd6ab36d-21fa-4513-a9d1-0867ca4420e8
- source file sha256
- 24c521d95bd19e54a354ae592997052a3a1b19254da1496b3a98a5e9bac4ed08
- payload sha256
- 4146599d0c1e57dc31f7ecf748a7e74301327768fd7d022472530dcd9053e755
- payload
- application numbers
- NDA219249
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-d9fd0952be548a47aaff
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT04191499
- occurrences
- context exact
- 14 CLINICAL STUDIES 14.1 Locally Advanced or Metastatic Breast Cancer INAVO120 INAVO120 (NCT04191499) was a randomized (1:1), double-blind, placebo-controlled trial evaluating the efficacy of ITOVEBI in combination with palbociclib and fulvestrant in adult pat
- end
- 100
- exact text
- NCT04191499
- start
- 89
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00700.json
- source file sha256
- 24c521d95bd19e54a354ae592997052a3a1b19254da1496b3a98a5e9bac4ed08
- source json pointer
- /results/33/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- dd6ab36d-21fa-4513-a9d1-0867ca4420e8
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 1092eb31426b725051010161e32e142d9eae381c2d5da10f745d67e482ca3310
- spl effective time
- 20260421
- spl set id
- 5de59f5b-e5db-410f-b692-658686ef4107
Preserved source evidence · Not medical advice