Alpelisib + Sacituzumab Govitecan for Breast Cancer
(ASSET Trial)
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Kansas Medical Center
Must not be taking: CYP3A inhibitors, BCRP inhibitors, Warfarin
Disqualifiers: Pregnancy, Diabetes, Cardiac disease, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This trial tests a combination of two drugs for patients with advanced HER2-negative breast cancer. One drug delivers chemotherapy directly to the cancer cells, and the other stops the cancer cells from growing.
Do I need to stop my current medications to join the trial?
The trial requires that you stop taking certain medications before starting the study. Specifically, you must discontinue strong inducers of CYP3A and BCRP inhibitors at least one week before the trial. If you are on medications that prolong the QT interval or are taking warfarin, you may need to stop or switch them as well.
What data supports the effectiveness of the drug Alpelisib in combination with Sacituzumab Govitecan for breast cancer?
Alpelisib has shown effectiveness in treating hormone receptor-positive, HER2-negative breast cancer with PIK3CA mutations, as demonstrated in the SOLAR-1 trial. Sacituzumab Govitecan, although not directly mentioned in the provided research, is known for its use in treating certain types of breast cancer, suggesting potential effectiveness when combined with Alpelisib.12345
What safety data exists for Sacituzumab Govitecan in humans?
Sacituzumab Govitecan has been studied in patients with advanced solid tumors, including breast cancer, and common side effects include nausea, neutropenia (low white blood cell count), diarrhea, fatigue, anemia (low red blood cell count), vomiting, hair loss, constipation, rash, decreased appetite, and abdominal pain. These side effects were observed in more than 25% of patients in clinical trials.678910
What makes the drug Alpelisib + Sacituzumab Govitecan unique for breast cancer treatment?
This drug combination is unique because it includes Sacituzumab Govitecan, an antibody-drug conjugate that targets Trop-2, a protein often found on cancer cells, and delivers a chemotherapy agent directly to the tumor, potentially increasing effectiveness and reducing side effects compared to standard chemotherapy.6891011
Eligibility Criteria
This trial is for adults with HER2-negative breast cancer that's either locally advanced or has spread (metastatic). They should have tried at least one chemotherapy and, if applicable, hormonal therapy. Participants need to be able to take oral medication, not have uncontrolled diabetes, no recent major surgery or active severe infections, and can't be pregnant or breastfeeding. Those with certain heart conditions or a history of severe allergic reactions are also excluded.Inclusion Criteria
My calcium levels are normal or slightly above but not concerning.
My brain metastases are stable, I'm not on steroids or specific seizure meds, and it's been over 21 days since their treatment.
Your absolute neutrophil count (a type of white blood cell) is at least 1500 per microliter. If you have a condition causing low neutrophil count, you may still be eligible if your count is between 1000-1500 and your doctor thinks the trial treatment won't increase your risk of infection too much.
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Exclusion Criteria
I have a GI condition that could affect how I absorb medication.
I had palliative radiation therapy less than 2 weeks ago or still have side effects from it.
I have lung inflammation or scarring.
See 26 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive alpelisib and sacituzumab govitecan in a 21-day cycle with dose escalation to determine the recommended phase II dose
21 days per cycle
Intravenous administration on days 1 and 8 of each cycle
Pharmacokinetics Assessment
Blood sampling for pharmacokinetics of alpelisib and sacituzumab govitecan
48 hours post-dose in cycle 1
Multiple blood sampling visits
Follow-up
Participants are monitored for safety and effectiveness after treatment
Estimated 24 months maximum
Treatment Details
Interventions
- Alpelisib (PI3K Inhibitor)
- Sacituzumab govitecan (Monoclonal Antibodies)
Trial OverviewThe study tests the combination of two drugs: Alpelisib and Sacituzumab Govitecan in treating metastatic or locally recurrent HER2-negative breast cancer. It aims to determine how safe this combination is and how effective it is in managing the disease.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Dose level 3: alpelisib 300 mg plus sacituzumab govitecan 10 mg/kgExperimental Treatment2 Interventions
Alpelisib: 300 mg by mouth daily Sacituzumab govitecan: 10 mg/kg intravenous on days 1 and 8 of each 21 (+/-2) day cycle
Group II: Dose level 2: alpelisib 250 mg plus sacituzumab govitecan 10 mg/kgExperimental Treatment2 Interventions
Alpelisib: 250 mg by mouth daily Sacituzumab govitecan: 10 mg/kg intravenous on days 1 and 8 of each 21 (+/-2) day cycle
Group III: Dose level 1: alpelisib 250 mg plus sacituzumab govitecan 8 mg/kgExperimental Treatment2 Interventions
Alpelisib: 250 mg by mouth daily Sacituzumab govitecan: 8 mg/kg intravenous on days 1 and 8 of each 21 (+/-2) day cycle
Alpelisib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Piqray for:
- Hormone receptor-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen
🇪🇺 Approved in European Union as Piqray for:
- Hormone receptor-positive, HER2-negative, PIK3CA-mutated, locally advanced or metastatic breast cancer in combination with fulvestrant
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The University of Kansas Clinical Research CenterFairway, KS
The University of Kansas Cancer Center - Overland ParkOverland Park, KS
The University of Kansas Cancer Center - Indian CreekOverland Park, KS
The University of Kansas Cancer CenterWestwood, KS
More Trial Locations
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Who Is Running the Clinical Trial?
University of Kansas Medical CenterLead Sponsor
Novartis PharmaceuticalsIndustry Sponsor
Gilead SciencesIndustry Sponsor
References
Pharmaceutical Approval Update. [2020]Alpelisib (Piqray) for HR-positive/HER2-negative, PIK3CA-mutated, advanced/ metastatic breast cancer; polatuzumab vedotin-piiq (Polivy) for diffuse large B-cell lymphoma; and eculizumab (Soliris) for neuromyelitis optica spectrum disorder.
Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations. [2021]Since the US FDA approval of everolimus/exemestane in July 2012, and of the first CDK 4/6 inhibitor, palbociclib, combined with endocrine treatment in February 2015, a third class of therapeutic compounds, the PI3K inhibitors, has been introduced to the arsenal of targeted therapies overcoming endocrine resistance in hormone receptor-positive metastatic breast cancer. Alpelisib (PIQRAY®) is the first of these novel agents yielding promising clinical results, giving an impetus to further development of tailored endocrine anticancer treatments. Herein, we review its pharmacodynamic and pharmacokinetic properties, safety and efficacy data, as well as Phase III SOLAR-1 trial, prompting FDA approval of alpelisib in hormone receptor-positive metastatic breast cancer harboring PIK3CA mutations. Furthermore, implications for clinical use and current research will also be discussed.
Alpelisib: First Global Approval. [2020]Alpelisib (Piqray™)-an orally available phosphatidylinositol 3-kinase (PI3K) inhibitor with specific activity against PI3K alpha (PI3Kα)-is being developed by Novartis for the treatment of breast cancer. Alpelisib has demonstrated efficacy in combination with fulvestrant as treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer in patients with a PIK3CA mutation and was recently approved for this indication in the USA. This article summarizes the milestones in the development of alpelisib leading to this first approval.
A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer. [2021]Label="PURPOSE">This study reports the MTD, recommended phase 2 dose (RP2D), and preliminary efficacy of alpelisib or buparlisib used in combination with tamoxifen plus goserelin in premenopausal patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC).
A Cohort Study of the Antitumor Efficacy and Toxicity Profile of Alpelisib for Metastatic or Locally Advanced HR+, HER2- Breast Cancer: A Single-Institution Experience. [2023]Alpelisib is approved in combination with endocrine therapy (ET) to treat patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) progressive metastatic breast cancer (MBC). The SOLAR-1 trial demonstrated the efficacy of this oral agent and showed that, while alpelisib improves outcomes compared to placebo, it is also associated with clinically relevant adverse events (AEs). There is a pressing need for improved knowledge on the effectiveness and tolerability of this agent in real-world patient populations.
Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease.
FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. [2022]On April 22, 2020, the FDA granted accelerated approval to sacituzumab govitecan-hziy (TRODELVY; Immunomedics, Inc.) for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Approval was based on data from the IMMU-132-01 trial, a single-arm, multicohort, multicenter, phase I/II trial of sacituzumab govitecan. The assessment of efficacy was based on 108 patients with mTNBC who had previously received at least two prior lines of therapy in the metastatic setting and who received sacituzumab govitecan 10 mg/kg i.v. The assessment of safety was based on 408 patients with advanced solid tumors who had received sacituzumab govitecan at doses up to 10 mg/kg i.v. The primary efficacy endpoint was investigator-assessed objective response rate (ORR) and duration of response (DoR) was a key secondary endpoint. The ORR was 33.3% [36/108; 95% confidence interval (CI), 24.6-43.1], and median DoR among responders was 7.7 months (95% CI, 4.9-10.8). The most common adverse reactions occurring in ≥25% of patients were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain. This article summarizes the FDA review process and data supporting the approval of sacituzumab govitecan.
The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer. [2022]Sacituzumab govitecan (SG) is an antineoplastic agent which combines a humanized monoclonal antibody binding to trophoblast cell surface antigen-2 (Trop-2)-expressing cancer cells, linked with cytotoxic moiety SN-38 (govitecan) with topoisomerase I inhibitor action. On 22 November 2021, a marketing authorization valid through the European Union (EU) was issued under the European Medicines Agency (EMA)'s accelerated assessment program for SG as monotherapy for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, including at least one of them for advanced disease. The assessment was based on results from an open-label, randomized, phase III trial to evaluate the safety, tolerability, pharmacokinetics and efficacy of SG versus treatment of physician's choice (TPC) in patients with mTNBC who received at least two prior treatments including at least one of them for advanced disease. The efficacy results in the overall population, based on mature data, showed a statistically significant improvement of SG over TPC in progression-free survival (PFS) and overall survival (OS). The median PFS was 4.8 months versus 1.7 months [hazard ratio (HR) = 0.43, n = 529; 95% CI 0.35-0.54; P 30%) side effects of SG were diarrhea, neutropenia, nausea, fatigue, alopecia, anemia, constipation and vomiting. The aim of this manuscript is to summarize the scientific review of the application leading to regulatory approval in the EU.
Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. [2019]Standard chemotherapy is associated with low response rates and short progression-free survival among patients with pretreated metastatic triple-negative breast cancer. Sacituzumab govitecan-hziy is an antibody-drug conjugate that combines a humanized monoclonal antibody, which targets the human trophoblast cell-surface antigen 2 (Trop-2), with SN-38, which is conjugated to the antibody by a cleavable linker. Sacituzumab govitecan-hziy enables delivery of high concentrations of SN-38 to tumors.
Safety and effectiveness of sacituzumab govitecan in patients with metastatic triple-negative breast cancer in real-world settings: first observations from an interdisciplinary breast cancer centre in Germany. [2023]Sacituzumab govitecan has been recently approved by the USFDA and EMA for the treatment of patients with metastatic triple-negative breast cancer (mTNBC). We report real-world safety and effectiveness in patients with mTNBC receiving sacituzumab govitecan treatment at a breast cancer centre in Germany.
Sacituzumab Govitecan: First Approval. [2021]Sacituzumab govitecan (sacituzumab govitecan-hziy; Trodelvy™) is a Trop-2-directed antibody conjugated to a topoisomerase I inhibitor (SN-38) that is being developed by Immunomedics for the treatment of solid tumours, including breast cancer. In April 2020, sacituzumab govitecan received accelerated approval in the USA for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Sacituzumab govitecan is undergoing phase III development for breast cancer in the USA and EU, and phase II development for urothelial cancer. It is also being explored for brain metastases, glioblastoma, endometrial cancer and prostate cancer. This article summarizes the milestones in the development of sacituzumab govitecan leading to this first approval for mTNBC.