NCT04191499进行中（未招募）2 期
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 325
- 试验地点
- 237
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo + Palbociclib + Fulvestrant
Placebo Comparator
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.
干预措施: Placebo (Drug)
Inavolisib + Palbociclib + Fulvestrant
Experimental
Participants will receive inavolisib, palbociclib, and fulvestrant.
干预措施: Inavolisib (Drug)
Inavolisib + Palbociclib + Fulvestrant
Experimental
Participants will receive inavolisib, palbociclib, and fulvestrant.
干预措施: Palbociclib (Drug)
Inavolisib + Palbociclib + Fulvestrant
Experimental
Participants will receive inavolisib, palbociclib, and fulvestrant.
干预措施: Fulvestrant (Drug)
Placebo + Palbociclib + Fulvestrant
Placebo Comparator
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.
干预措施: Palbociclib (Drug)
Placebo + Palbociclib + Fulvestrant
Placebo Comparator
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.
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to 3.7 years
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.
次要结局
- Percentage of Participants With Objective Response Rate (ORR)(Up to approximately 6 years)
- Percentage of Participants With Best Overall Response Rate (BOR)(Up to approximately 6 years)
- Duration of Response (DOR)(Up to approximately 6 years)
- Percentage of Participants With Clinical Benefit Rate (CBR)(Up to approximately 6 years)
- Overall Survival (OS)(Up to approximately 6 years)
- Time to Deterioration (TTD) in Pain(From randomization to first documentation of a ≥ 2-point increase (Up to approximately 6 years))
- TTD in Physical Function (PF)(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)])
- TTD in Role Function (RF)(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)])
- TTD in Global Health Status (GHS)(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)])
- Number of Participants With Adverse Events (AEs)(Up to approximately 6 years)
- Plasma Concentration of Inavolisib(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))
- Plasma Concentration of Palbociclib(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))
- Plasma Concentration of Fulvestrant(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))
研究者
研究点 (237)
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相关资讯
Major Advances in Breast Cancer Treatment Highlighted in 2024• Inavolisib, combined with palbociclib and fulvestrant, received FDA approval for HR+/HER2-, PIK3CA-mutated advanced breast cancer, offering a new targeted therapy option.
• Ribociclib was approved for adjuvant treatment of HR+/HER2- early breast cancer with high recurrence risk, based on improved invasive disease-free survival in the NATALEE trial.
• Olaparib demonstrated a significant overall survival benefit in BRCA-mutated, HER2-negative early breast cancer, marking the first PARP inhibitor to achieve this milestone.
• Fam-trastuzumab deruxtecan-nxki (T-DXd) showed statistically significant progression-free survival improvement in HR+/HER2-low metastatic breast cancer after endocrine therapy.last yearFDA Approvals of Ribociclib and Inavolisib Reshape HR+ Breast Cancer Treatment• Ribociclib's approval for adjuvant use in high-risk HR+/HER2- early breast cancer marks a significant advancement, potentially benefiting a broader patient population.
• Inavolisib, combined with palbociclib and fulvestrant, gains FDA approval for endocrine-resistant, PIK3CA-mutated HR+/HER2- advanced breast cancer, improving progression-free survival.
• The FDA emphasizes the need for increased diversity in clinical trials and post-marketing studies to ensure the safety and efficacy of new drugs across all patient populations.
• Dose optimization strategies, like those promoted by Project Optimus, are crucial for balancing efficacy and toxicity in novel targeted therapies for breast cancer.last yearInavolisib Regimen Significantly Improves Survival in PIK3CA-Mutated Breast Cancer- The INAVO120 phase 3 trial demonstrated that inavolisib plus fulvestrant and palbociclib significantly improved progression-free survival (PFS) in patients with HR+, HER2–, PIK3CA-mutated breast cancer.
- The inavolisib regimen reduced the risk of disease progression or death by 57% compared to palbociclib alone, with a median PFS of 15.0 months versus 7.3 months.
- Overall survival data showed a positive trend with the inavolisib regimen, with a stratified hazard ratio of 0.64, indicating a potential survival benefit.
- The FDA approved the inavolisib regimen in October 2024 for HR+, HER2–, locally advanced or metastatic breast cancer, based on the INAVO120 trial data.last yearFDA Approves Inavolisib Plus Palbociclib and Fulvestrant for PIK3CA-Mutated, HR+/HER2- Advanced Breast Cancer• The FDA approved inavolisib in combination with palbociclib and fulvestrant for adults with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative advanced or metastatic breast cancer.
• The approval was based on the INAVO120 trial, which demonstrated a significant improvement in progression-free survival compared to placebo plus palbociclib and fulvestrant.
• Patients receiving the inavolisib regimen achieved an objective response rate of 58% compared to 25% in the placebo arm, with a median duration of response of 18.4 months vs 9.6 months, respectively.
• Inavolisib's manageable toxicity profile, particularly in patients without diabetes or glucose intolerance, makes it a valuable option for those with poor prognosis, hormone receptor-positive breast cancer.last yearInavolisib Triples Progression-Free Survival in Advanced Breast Cancer• Roche's Itovebi (inavolisib) combined with palbociclib and fulvestrant significantly improved outcomes in advanced breast cancer patients.
• The Phase III INAVO120 study showed a 57% reduction in the risk of disease progression or death compared to palbociclib and fulvestrant alone.
• The FDA approved the inavolisib-based regimen as a first-line treatment for HR-positive, HER2-negative breast cancer with PIK3CA mutation.
• The PIK3CA mutation is present in approximately 40 percent of HR-positive metastatic breast cancers.last year
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