A Phase Ib/II, Open-label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic Breast Cancer (Morpheus-panBC)
概览
- 阶段
- 1 期
- 干预措施
- Atezolizumab
- 疾病 / 适应症
- Metastatic Breast Cancer
- 发起方
- Hoffmann-La Roche
- 入组人数
- 792
- 试验地点
- 73
- 主要终点
- Objective Response Rate (ORR)
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
This is an umbrella study evaluating the efficacy and safety of multiple treatment combinations in participants with metastatic or inoperable locally advanced breast cancer.
The study will be performed in two stages. During Stage 1, six cohorts will be enrolled in parallel in this study:
Cohort 1 will consist of programmed death-ligand 1 (PD-L1)-positive participants who have received no prior systemic therapy for metastatic or inoperable locally advanced triple-negative breast cancer (TNBC) (first-line [1L] PD-L1+ cohort).
Cohort 2 will consist of participants who had disease progression during or following 1L treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not received cancer immunotherapy (CIT) (second-line [2L] CIT-naïve cohort).
Cohort 3, 5, and 6 will consist of participants with locally advanced or metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative disease with one or more PIK3CA mutations.
Cohort 4 will consist of participants with locally advanced or metastatic HER2+ /HER2-low disease with one or more PIK3CA mutations who had disease progression on standard-of-care therapies (HER2+ /HER2-low cohort).
In each cohort, eligible participants will initially be assigned to one of several treatment arms (Stage 1). During Stage 2, participants in the 2L CIT-naïve cohort who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment combination, provided Stage 2 is open for enrollment and all eligibility criteria are met.
研究者
入排标准
入选标准
- •Patients must meet all of the following criteria to qualify for Stage 1 (all cohorts) and to qualify for Stage 2 (2L CIT-naïve cohort):
- •Age \>/= 18 years at the time of signing Informed Consent Form
- •Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- •Able to comply with the study protocol, in the investigator's judgment
- •Metastatic or inoperable locally advanced breast cancer
- •Measurable disease (at least one target lesion) according to RECIST v1.1
- •Life expectancy \>/= 3 months, as determined by the investigator
- •Tumor accessible for biopsy, unless archival tissue is available
- •Availability of a representative tumor specimen that is suitable for biomarker analysis via central testing
- •Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment
排除标准
- •Exclusion Criteria for Stage 1
- •Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40 agonists or interleukin-2 (IL-2) or IL-2-like compounds
- •Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
- •Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
- •Eligibility only for the control arm
- •Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort)
- •Adverse events from prior anti-cancer therapy that have not resolved to Grade \</= 1 or better with the exception of alopecia of any grade and Grade \</= 2 peripheral neuropathy
- •Treatment with investigational therapy within 28 days prior to initiation of study treatment
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
- •Uncontrolled tumor-related pain
研究组 & 干预措施
Atezolizumab + Nab-Paclitaxel
1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus nab-paclitaxel until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
干预措施: Atezolizumab
Atezolizumab + Nab-Paclitaxel
1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus nab-paclitaxel until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
干预措施: Nab-Paclitaxel
Atezolizumab + Nab-Paclitaxel + Tocilizumab
1L PD-L1-positive participants will receive combination treatment with atezolizumab plus nab-paclitaxel and tocilizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
干预措施: Atezolizumab
Atezolizumab + Nab-Paclitaxel + Tocilizumab
1L PD-L1-positive participants will receive combination treatment with atezolizumab plus nab-paclitaxel and tocilizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
干预措施: Tocilizumab
Atezolizumab + Nab-Paclitaxel + Tocilizumab
1L PD-L1-positive participants will receive combination treatment with atezolizumab plus nab-paclitaxel and tocilizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
干预措施: Nab-Paclitaxel
Atezolizumab + Sacituzumab Govitecan
1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus sacituzumab govitecan until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
干预措施: Atezolizumab
Atezolizumab + Sacituzumab Govitecan
1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus sacituzumab govitecan until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed.
干预措施: Sacituzumab Govitecan
Capecitabine
2L CIT-naïve participants will receive capecitabine until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1). Participants who progressed on treatment may have the option of receiving atezolizumab along with chemotherapy (chemo) during stage 2, provided they meet the eligibility criteria. Enrollment is closed.
干预措施: Capecitabine
Atezolizumab + Ipatasertib
2L CIT-naïve participants will receive doublet combination treatment with atezolizumab plus ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete.
干预措施: Atezolizumab
Atezolizumab + Ipatasertib
2L CIT-naïve participants will receive doublet combination treatment with atezolizumab plus ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete.
干预措施: Ipatasertib
Atezolizumab + SGN-LIV1A
2L CIT-naïve participants will receive doublet combination treatment with atezolizumab plus SGNLIV1A until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Patients who experience loss of clinical benefit as determined by the investigator or unacceptable toxicity related to SGN-LIV1A will be given the option of receiving Atezolizumab + chemo during Stage 2, provided they meet the eligibility criteria. Enrollment is closed.
干预措施: Atezolizumab
Atezolizumab + SGN-LIV1A
2L CIT-naïve participants will receive doublet combination treatment with atezolizumab plus SGNLIV1A until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Patients who experience loss of clinical benefit as determined by the investigator or unacceptable toxicity related to SGN-LIV1A will be given the option of receiving Atezolizumab + chemo during Stage 2, provided they meet the eligibility criteria. Enrollment is closed.
干预措施: SGN-LIV1A
Atezolizumab + Selicrelumab + Bevacizumab
2L-CIT-naïve participants will receive doublet combination treatment with atezolizumab plus selicrelumab and bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete.
干预措施: Atezolizumab
Atezolizumab + Selicrelumab + Bevacizumab
2L-CIT-naïve participants will receive doublet combination treatment with atezolizumab plus selicrelumab and bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete.
干预措施: Bevacizumab
Inavolisib + Ribociclib (Dose #1) + Letrozole
HR+ participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Ribociclib (Dose #1)
Atezolizumab + Selicrelumab + Bevacizumab
2L-CIT-naïve participants will receive doublet combination treatment with atezolizumab plus selicrelumab and bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete.
干预措施: Selicrelumab
Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin)
2L CIT-naïve participants enrolled in the active comparator arm who experience disease progression per RECIST v1.1 and 2L CIT-naïve participants enrolled in an experimental arm who experience loss of clinical benefit as determined by the investigator may receive doublet combination treatment with atezolizumab plus chemo (gemcitabine + carboplatin or eribulin) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed and participant follow-up is complete.
干预措施: Atezolizumab
Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin)
2L CIT-naïve participants enrolled in the active comparator arm who experience disease progression per RECIST v1.1 and 2L CIT-naïve participants enrolled in an experimental arm who experience loss of clinical benefit as determined by the investigator may receive doublet combination treatment with atezolizumab plus chemo (gemcitabine + carboplatin or eribulin) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed and participant follow-up is complete.
干预措施: Chemotherapy (Gemcitabine + Carboplatin or Eribulin)
Inavolisib + Abemaciclib + Fulvestrant
HR+ participants will receive treatment with inavolisib plus abemaciclib plus fulvestrant until unacceptable toxicity or disease progression determined by the investigator according to RECIST v1.1.
干预措施: Abemaciclib
Inavolisib + Abemaciclib + Fulvestrant
HR+ participants will receive treatment with inavolisib plus abemaciclib plus fulvestrant until unacceptable toxicity or disease progression determined by the investigator according to RECIST v1.1.
干预措施: Fulvestrant
Inavolisib + Abemaciclib + Fulvestrant
HR+ participants will receive treatment with inavolisib plus abemaciclib plus fulvestrant until unacceptable toxicity or disease progression determined by the investigator according to RECIST v1.1.
干预措施: Inavolisib
Inavolisib + Ribociclib (Dose #1) + Fulvestrant
HR+ participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Fulvestrant
Inavolisib + Ribociclib (Dose #1) + Fulvestrant
HR+ participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Ribociclib (Dose #1)
Inavolisib + Ribociclib (Dose #1) + Fulvestrant
HR+ participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Inavolisib
Inavolisib + Ribociclib (Dose #1) + Letrozole
HR+ participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Letrozole
Inavolisib + Ribociclib (Dose #1) + Letrozole
HR+ participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Inavolisib
Inavolisib + Ribociclib (Dose #2) + Fulvestrant
HR+ participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Fulvestrant
Inavolisib + Ribociclib (Dose #2) + Fulvestrant
HR+ participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Ribociclib (Dose #2)
Inavolisib + Ribociclib (Dose #2) + Fulvestrant
HR+ participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Inavolisib
Inavolisib + Ribociclib (Dose #2) + Letrozole
HR+ participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Ribociclib (Dose #2)
Inavolisib + Ribociclib (Dose #2) + Letrozole
HR+ participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Letrozole
Inavolisib + Ribociclib (Dose #2) + Letrozole
HR+ participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Inavolisib
Inavolisib + Abemaciclib + Letrozole
HR+ participants will receive treatment with inavolisib plus abemaciclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Abemaciclib
Inavolisib + Abemaciclib + Letrozole
HR+ participants will receive treatment with inavolisib plus abemaciclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Letrozole
Inavolisib + Abemaciclib + Letrozole
HR+ participants will receive treatment with inavolisib plus abemaciclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Inavolisib
Inavolisib (Dose #1) + Trastuzumab Deruxtecan
HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Inavolisib (Dose #1)
Inavolisib (Dose #1) + Trastuzumab Deruxtecan
HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Trastuzumab Deruxtecan
Inavolisib (Dose #2) + Trastuzumab Deruxtecan
HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Trastuzumab Deruxtecan
Inavolisib (Dose #2) + Trastuzumab Deruxtecan
HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Inavolisib (Dose #2)
Empagliflozin (Empa) + Inavolisib (Inavo) + Fulvestrant (Fulv) ± Palbociclib (Palbo)
Participants with locally advanced or metastatic, HR+, HER2- participants will receive empagliflozin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Fulvestrant
Empagliflozin (Empa) + Inavolisib (Inavo) + Fulvestrant (Fulv) ± Palbociclib (Palbo)
Participants with locally advanced or metastatic, HR+, HER2- participants will receive empagliflozin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Inavolisib
Empagliflozin (Empa) + Inavolisib (Inavo) + Fulvestrant (Fulv) ± Palbociclib (Palbo)
Participants with locally advanced or metastatic, HR+, HER2- participants will receive empagliflozin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Empagliflozin
Empagliflozin (Empa) + Inavolisib (Inavo) + Fulvestrant (Fulv) ± Palbociclib (Palbo)
Participants with locally advanced or metastatic, HR+, HER2- participants will receive empagliflozin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Palbociclib
Metformin (Metf) + Inavolisib + Fulvestrant ± Palbociclib
Participants with locally advanced or metastatic, HR+, HER2- participants will receive metformin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Fulvestrant
Metformin (Metf) + Inavolisib + Fulvestrant ± Palbociclib
Participants with locally advanced or metastatic, HR+, HER2- participants will receive metformin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Inavolisib
Metformin (Metf) + Inavolisib + Fulvestrant ± Palbociclib
Participants with locally advanced or metastatic, HR+, HER2- participants will receive metformin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Palbociclib
Metformin (Metf) + Inavolisib + Fulvestrant ± Palbociclib
Participants with locally advanced or metastatic, HR+, HER2- participants will receive metformin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Metformin
Inavolisib + Atirmociclib (Atirmo) + Fulvestrant
Participants will receive inavolisib plus atirmociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Fulvestrant
Inavolisib + Atirmociclib (Atirmo) + Fulvestrant
Participants will receive inavolisib plus atirmociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Inavolisib
Inavolisib + Atirmociclib (Atirmo) + Fulvestrant
Participants will receive inavolisib plus atirmociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.
干预措施: Atirmociclib
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Baseline until disease progression or loss of clinical benefit (up to approximately 10 years)
次要结局
- Overall Survival (OS)(Randomization to death from any cause, through the end of study (up to approximately 10 years))
- Overall Survival (at specific time-points)(12 and 18 months)
- Percentage of Participants with Adverse Events(Baseline to end of study (up to approximately 10 years))
- Progression Free Survival (PFS)(Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (up to approximately 10 years) as determined by the investigator according to RECIST v1.1)
- Disease Control Rate (DCR)(Baseline through end of study (up to approximately 10 years))
- Duration of Response (DOR)(Randomization until first occurrence of a documented objective response to the first recorded occurrence of disease progression or death from any cause (whichever occurs first), through end of study (up to approximately 10 years))