Personalized Adaptive Novel Agents for Breast Cancer
(I-SPY Trial)
Recruiting in Palo Alto (17 mi)
+36 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: QuantumLeap Healthcare Collaborative
Must not be taking: Investigational agents
Disqualifiers: Infections, Heart failure, Angina, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing new medicines along with regular cancer treatment to find the best combinations for breast cancer patients. It focuses on identifying which treatments work best based on specific cancer characteristics. Early signs of success are monitored using MRI scans and tests on blood and tissue samples.
Do I need to stop my current medications for the trial?
The trial information does not specify if you need to stop taking your current medications. However, you cannot use any investigational agents within 30 days of starting the study treatment.
What data supports the effectiveness of the drug combination Amcenestrant + Abemaciclib for breast cancer?
Research from the MONARCH3 and MonarchE studies shows that abemaciclib, when added to endocrine therapy, significantly improves progression-free survival and disease-free survival in patients with hormone receptor-positive, HER2-negative breast cancer.
12345Is the combination of abemaciclib with endocrine therapy safe for breast cancer treatment?
Abemaciclib, when combined with endocrine therapy, has been shown to improve outcomes in hormone receptor-positive, HER2-negative breast cancer, but it has different toxicity profiles that require careful monitoring. The safety profiles of these combinations are generally predictable and manageable, though there is an increased risk of potentially serious toxicities.
16789What makes the drug combination of Amcenestrant and Abemaciclib unique for breast cancer treatment?
The combination of Amcenestrant and Abemaciclib is unique because it targets hormone receptor-positive, HER2-negative breast cancer by combining a selective estrogen receptor degrader (Amcenestrant) with a CDK4/6 inhibitor (Abemaciclib), which has shown effectiveness in improving progression-free survival in advanced cases.
1231011Eligibility Criteria
This trial is for adults over 18 with invasive breast cancer, who haven't had chemotherapy or radiation for it. They must be non-pregnant, have normal organ function, and no metal implants incompatible with MRI. The cancer should be measurable in the breast and not spread far (specific stages). All hormone receptor statuses are eligible.Inclusion Criteria
Ability to understand and willingness to sign a written informed consent document (I-SPY 2 TRIAL Consent #2)
I am fully active or can carry out light work.
My tumor's hormone and HER2 status fits the study's specific criteria.
+13 more
Exclusion Criteria
I do not have any severe illnesses or social situations that would prevent me from following the study's requirements.
Use of any other investigational agents within 30 days of starting study treatment
You have had allergic reactions to similar drugs or medications in the past.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive novel investigational agents in sequence with standard chemotherapy to assess efficacy based on molecular characteristics
12-24 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 weeks
Extension
Participants may continue to receive treatment with novel agents if they show a high probability of improved efficacy
Participant Groups
The study tests various new drugs against different types of breast tumors to personalize treatment. It uses MRI and tissue/blood samples before surgery to predict success. Drugs include Datopotamab deruxtecan, Durvalumab, Trilaciclib combinations, ABT-888 among others.
42Treatment groups
Experimental Treatment
Active Control
Group I: Zanidatamab in Block A and followed by SOC in block BExperimental Treatment1 Intervention
Novel investigational Agent followed by SOC
Group II: VSV-IFNβ-NIS (VOYAGER V1™; VV1) + Cemiplimab in Block A and followed by SOC in block BExperimental Treatment1 Intervention
Novel investigational Agent followed by SOC
Group III: TucatinibExperimental Treatment1 Intervention
Arm is closed.
Group IV: Trilaciclib with or without trastuzumab + pertuzumabExperimental Treatment1 Intervention
Novel Investigational Agent. Arm is closed.
Group V: Talazoparib plus IrinotecanExperimental Treatment1 Intervention
Arm is closed.
Group VI: T-DM1 and PertuzumabExperimental Treatment1 Intervention
Arm is closed.
Group VII: Sarilumab + Cemiplimab + Paclitaxel in Block B followed by SOC Block CExperimental Treatment1 Intervention
Novel investigational Agent
Group VIII: SYD985 ([vic-]trastuzumab duocarmazine)Experimental Treatment1 Intervention
Novel Investigational Agent. Arm is closed.
Group IX: SGN-LIV1AExperimental Treatment1 Intervention
Arm is closed.
Group X: SD-101 + PembrolizumabExperimental Treatment1 Intervention
Arm is closed.
Group XI: Rilvegostomig + TDXd in Block A and followed by SOC in Block BExperimental Treatment1 Intervention
Novel investigational Agent
Group XII: Pembrolizumab 8 cycleExperimental Treatment1 Intervention
Arm is closed.
Group XIII: Pembrolizumab 4 cycleExperimental Treatment1 Intervention
Arm is closed.
Group XIV: Patritumab with or without TrastuzumabExperimental Treatment1 Intervention
Arm is closed.
Group XV: PLX3397Experimental Treatment1 Intervention
Arm is closed.
Group XVI: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumabExperimental Treatment1 Intervention
Novel Investigational Agent. Arm is closed.
Group XVII: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumabExperimental Treatment1 Intervention
Novel Investigational Agent. Arm is closed.
Group XVIII: NeratinibExperimental Treatment1 Intervention
Arm is closed.
Group XIX: MK-2206 with or without TrastuzumabExperimental Treatment1 Intervention
Arm is closed.
Group XX: GanetespibExperimental Treatment1 Intervention
Arm is closed.
Group XXI: Endocrine Optimization Pilot: LasofoxifeneExperimental Treatment1 Intervention
Novel investigational Agent
Group XXII: Endocrine Optimization Pilot: Amcenestrant MonotherapyExperimental Treatment1 Intervention
Novel Investigational Agent. Arm is closed.
Group XXIII: Endocrine Optimization Pilot: Amcenestrant + LetrozoleExperimental Treatment1 Intervention
Novel Investigational Agent. Arm is closed.
Group XXIV: Endocrine Optimization Pilot: Amcenestrant + AbemaciclibExperimental Treatment1 Intervention
Novel Investigational Agent. Arm is closed.
Group XXV: Endocrine Optimization Pilot: ARV-471 + LetrozoleExperimental Treatment1 Intervention
Novel investigational Agent
Group XXVI: Endocrine Optimization Pilot: ARV-471 + AbemaciclibExperimental Treatment1 Intervention
Novel investigational Agent
Group XXVII: Endocrine Optimization Pilot: ARV-471Experimental Treatment1 Intervention
Novel investigational Agent
Group XXVIII: Endocrine Optimization Pilot: (Z)-Endoxifen + AbemaciclibExperimental Treatment1 Intervention
Novel investigational Agent
Group XXIX: Endocrine Optimization Pilot: (Z)-EndoxifenExperimental Treatment1 Intervention
Novel investigational Agent
Group XXX: Durvalumab plus OlaparibExperimental Treatment1 Intervention
Arm is closed.
Group XXXI: Datopotamab Deruxtecan in Block A and followed by SOC in block BExperimental Treatment1 Intervention
Novel investigational Agent followed by SOC
Group XXXII: Datopotamab Deruxtecan + Durvalumab in Block A and followed by SOC in block BExperimental Treatment1 Intervention
Novel investigational Agent followed by SOC
Group XXXIII: DAN222 + Niraparib in Block A and followed by SOC in Block BExperimental Treatment1 Intervention
Novel investigational Agent
Group XXXIV: Cemiplimab plus REGN3767Experimental Treatment1 Intervention
Novel Investigational Agent. Arm is closed.
Group XXXV: CemiplimabExperimental Treatment1 Intervention
Novel Investigational Agent. Arm is closed.
Group XXXVI: ARX788 in Block A and followed by SOC in Block BExperimental Treatment1 Intervention
Novel investigational Agent followed by SOC
Group XXXVII: ARX788 + Cemiplimab in Block A and followed by SOC in Block BExperimental Treatment1 Intervention
Novel investigational Agent followed by SOC. Arm is closed.
Group XXXVIII: AMG 479 plus MetforminExperimental Treatment1 Intervention
Arm is closed.
Group XXXIX: AMG 386 with or without TrastuzumabExperimental Treatment2 Interventions
Arm is closed.
Group XL: ABT-888Experimental Treatment1 Intervention
Arm is closed.
Group XLI: Standard TherapyActive Control1 Intervention
Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status.
Group XLII: Pertuzumab and TrastuzumabActive Control1 Intervention
Novel Control Investigational Agent. Arm is closed.
Amcenestrant + Abemaciclib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as SAR439859 + Verzenio for:
- Advanced breast cancer
- HR-positive, HER2-negative breast cancer
🇪🇺 Approved in European Union as Amcenestrant + Abemaciclib for:
- Locally advanced or metastatic breast cancer
- HR-positive, HER2-negative breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Laura and Isaac Perlmutter Cancer Center / NYU Langone HealthNew York, NY
Emory UniversityAtlanta, GA
University of California San DiegoLa Jolla, CA
University Pittsburgh Medical CenterPittsburgh, PA
More Trial Locations
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Who Is Running the Clinical Trial?
QuantumLeap Healthcare CollaborativeLead Sponsor
References
Abemaciclib Reigns Over Breast Cancer in MonarchE. [2021]Adding abemaciclib to adjuvant endocrine therapy may lead to better outcomes in hormone receptor-positive, HER2-negative, high-risk, early breast cancer. In a phase III trial, the combination improved invasive disease-free survival and distant relapse-free survival compared with endocrine therapy alone. However, a trial of another CDK4/6 inhibitor came to the opposite conclusion.
First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]Interim data from the MONARCH3 study indicate that abemaciclib is an effective first-line therapy for advanced ER-positive, HER2-negative breast cancer. Adding the investigational CDK4/6 inhibitor to letrozole significantly improved patients' progression-free survival, compared with those given a placebo alongside endocrine therapy.
Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. [2023]In the FLIPPER trial, palbociclib/fulvestrant significantly improved progression-free survival (PFS) compared with placebo/fulvestrant in postmenopausal women with HR+/HER2- advanced breast cancer (ABC).
MONARCH 2: Subgroup Analysis of Patients Receiving Abemaciclib Plus Fulvestrant as First-Line and Second-Line Therapy for HR+, HER2--Advanced Breast Cancer. [2022]Label="PURPOSE">In MONARCH 2, abemaciclib plus fulvestrant significantly prolonged progression-free survival (PFS) and overall survival (OS) versus placebo plus fulvestrant in patients with hormone receptor positive (HR+), HER2- advanced breast cancer. This exploratory analysis assessed the efficacy of abemaciclib plus fulvestrant across subgroups of patients receiving study therapy as first- or second-line treatment for metastatic disease.
A Gene Panel Associated With Abemaciclib Utility in ESR1-Mutated Breast Cancer After Prior Cyclin-Dependent Kinase 4/6-Inhibitor Progression. [2023]Label="PURPOSE">For patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), first-line treatment is endocrine therapy (ET) plus cyclin-dependent kinase 4/6 inhibition (CDK4/6i). After disease progression, which often comes with ESR1 resistance mutations (ESR1-MUT), which therapies to use next and for which patients are open questions. An active area of exploration is treatment with further CDK4/6i, particularly abemaciclib, which has distinct pharmacokinetic and pharmacodynamic properties compared with the other approved CDK4/6 inhibitors, palbociclib and ribociclib. We investigated a gene panel to prognosticate abemaciclib susceptibility in patients with ESR1-MUT MBC after palbociclib progression.
Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. [2023]Abemaciclib was recently approved by the European Medicines Agency in combination with adjuvant endocrine therapy (ET) for adult patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive early breast cancer (EBC) at high risk of recurrence.
The Role of CDK4/6 Inhibitors in Breast Cancer. [2020]Oral inhibitors of CDK4/6 have been shown to increase response rates and prolong disease control when combined with endocrine therapy in hormone-responsive (HR+) HER2-negative advanced breast cancer. Palbociclib, ribociclib and abemaciclib are all approved in combination with non-steroidal aromatase inhibitors in first-line therapy for post-menopausal women, with a 40-45% improvement in progression-free survival seen with the addition of any of these CDK4/6 inhibitors. Additional approved indications, including first- and second-line combination therapy for pre-menopausal women, combination with fulvestrant and use as monotherapy, vary with each agent and are reviewed fully in the subsequent texts. These agents also differ in their toxicity profiles and monitoring requirements, and prescribers should be aware of the individual requirements for each agent. Current clinical trials are investigating the expanded use of these agents in other breast cancer subtypes, such as HER2-positive and triple-negative breast cancer, as well as in the adjuvant and neoadjuvant treatments of early breast cancer. Resistance to CDK4/6 inhibition can occur through multiple mechanisms. Rational combinations with other therapies, such as PI3K inhibitors, HER2-directed therapies and immunotherapy, are being explored.
Enhancing Endocrine Therapy Combination Strategies for the Treatment of Postmenopausal HR+/HER2- Advanced Breast Cancer. [2018]Breast cancer (BC) is the most common malignancy in women worldwide, with approximately two-thirds having hormone receptor-positive (HR+) tumors. New endocrine therapy (ET) strategies include combining ET agents as well as adding inhibitors targeting growth factors, angiogenesis, the mechanistic target of rapamycin, phosphoinositide 3-kinase (PI3K), or cyclin-dependent kinase 4/6 to ET. Level 1 evidence supports use of fulvestrant plus anastrozole or palbociclib plus letrozole as first-line therapy for HR+/HER- advanced BC with special consideration for the former in ET-naïve patients, as well as everolimus plus exemestane or palbociclib plus fulvestrant as second-line therapy with special consideration in select first-line patients. Although the safety profiles of these combinations are generally predictable and manageable, both everolimus and palbociclib are associated with an increased risk of potentially serious or early-onset toxicities requiring individualized a priori adverse event risk stratification, earlier and more rigorous agent-specific monitoring, and patient education. Although each of these combinations improves progression-free survival, none with the exception of anastrazole plus fulvestrant have demonstrated improved overall survival. PI3K catalytic-α mutations assessed from circulating tumor DNA represent the first potentially viable serum biomarker for the selection of ET combinations, and new data demonstrate the feasibility of this minimally invasive technique as an alternative to traditional tissue analysis. Therapeutic ratios of select ET combinations support their use in first- and second-line settings, but optimal sequencing has yet to be determined.
Effectiveness of Alpelisib + Fulvestrant Compared with Real-World Standard Treatment Among Patients with HR+, HER2-, PIK3CA-Mutated Breast Cancer. [2022]The BYLieve trial (NCT03056755) confirmed efficacy and safety of alpelisib with fulvestrant for hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC), after cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with an aromatase inhibitor (AI) as immediate prior therapy. Further analyses were performed to compare efficacy from BYLieve with effectiveness of standard treatment in the real-world setting.
Therapeutic innovations in breast cancer. [2019]Managing endocrine resistance and resistance to endocrine therapy for ER+ HER2- breast cancer with the CDK 4/6 inhibitors in the metastatic setting. New antibodies drug conjugates for HER2+ and TNBC. Targeting DNA damage and synthetic lethality strategies with PARP inhibitors for breast cancer patients harboring BRCA mutation. Immunotherapies in 1st line metastatic setting of TNBC.
Single-Agent Abemaciclib Active in Breast Cancer. [2019]According to results from a phase II study, abemaciclib shows single-agent activity in women with metastatic HER2-negative, ER-positive breast cancer whose disease has progressed on endocrine therapy and chemotherapy. The objective response rate to this investigational CDK4/6 inhibitor was 19.7%, with 28.2% of responses lasting at least a year.