Alpelisib + Sacituzumab Govitecan for Breast Cancer

(ASSET Trial)

Recruiting at 6 trial locations

Overseen By Priyanka Sharma, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Kansas Medical Center

Must not be taking: CYP3A inhibitors, BCRP inhibitors, Warfarin

Disqualifiers: Pregnancy, Diabetes, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 21 days per cycle

18 Participants Needed

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 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. ^{1 2 3 4 5}

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. ^{1 3 4 5 6}

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. ^{7 8 9 10 11}

Research Team

Priyanka Sharma, MD

Principal Investigator

University of Kansas Medical Center

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.

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.

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
• Sacituzumab govitecan

Trial Overview The 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

Group I: Dose level 3: alpelisib 300 mg plus sacituzumab govitecan 10 mg/kg Experimental Treatment 2 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/kg Experimental Treatment 2 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/kg Experimental Treatment 2 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

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Gilead Sciences

Industry Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Findings from Research

Alpelisib (Piqray) is effective for treating advanced or metastatic breast cancer that is HR-positive, HER2-negative, and has PIK3CA mutations, targeting specific genetic alterations to improve treatment outcomes.

Polatuzumab vedotin-piiq (Polivy) is used for diffuse large B-cell lymphoma, while eculizumab (Soliris) is indicated for neuromyelitis optica spectrum disorder, highlighting the development of targeted therapies for specific cancer types and autoimmune conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Choy, M.[2020]

Alpelisib (PIQRAY®) is the first PI3K inhibitor approved for treating hormone receptor-positive metastatic breast cancer with PIK3CA mutations, showing promising clinical results that support its use in overcoming endocrine resistance.

The review highlights the pharmacodynamic and pharmacokinetic properties of alpelisib, along with safety and efficacy data from the Phase III SOLAR-1 trial, which led to its FDA approval, indicating its potential as a tailored treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations. Mavratzas, A., Marmé, F.[2021]

Alpelisib (Piqray™) is an oral PI3K inhibitor specifically targeting PI3Kα, showing efficacy in treating hormone receptor-positive, HER2-negative breast cancer in patients with a PIK3CA mutation.

The drug has been approved in the USA for use in combination with fulvestrant, marking a significant milestone in its development for breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpelisib: First Global Approval. Markham, A.[2020]

The study established the recommended phase 2 doses (RP2D) for alpelisib (350 mg) and buparlisib (100 mg) when combined with tamoxifen and goserelin in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, showing that both combinations were well-tolerated.

Patients treated with alpelisib experienced a longer progression-free survival of 25.2 months compared to 20.6 months for those on buparlisib, suggesting that alpelisib may be a more effective option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Alpelisib or Buparlisib Combined with Tamoxifen Plus Goserelin in Premenopausal Women with HR-Positive HER2-Negative Advanced Breast Cancer. Lu, YS., Lee, KS., Chao, TY., et al.[2021]

In a study of 76 women with hormone receptor-positive, HER2-negative metastatic breast cancer, alpelisib combined with endocrine therapy demonstrated a median progression-free survival of 5.2 months, indicating its effectiveness in a real-world setting.

However, about 31.6% of patients had to permanently discontinue alpelisib due to adverse events, with hyperglycemia being the most common serious side effect, highlighting the need for careful monitoring of patients on this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Sarfraz, H., Bari, S., Whiting, J., et al.[2023]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

Sacituzumab govitecan-hziy (TRODELVY) received accelerated FDA approval for treating metastatic triple-negative breast cancer (mTNBC) based on a trial involving 108 patients, showing an objective response rate of 33.3% and a median duration of response of 7.7 months.

The safety profile was assessed in a larger group of 408 patients, with common side effects including nausea, neutropenia, and fatigue, occurring in 25% or more of patients, indicating that while effective, the treatment can have significant adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. Wahby, S., Fashoyin-Aje, L., Osgood, CL., et al.[2022]

Sacituzumab govitecan (SG) has been approved in the EU for treating adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have undergone at least two prior systemic therapies, showing significant improvements in progression-free survival (4.8 months vs. 1.7 months) and overall survival (11.8 months vs. 6.9 months) compared to treatment of physician's choice.

The most common side effects of SG include diarrhea, neutropenia, nausea, fatigue, alopecia, anemia, constipation, and vomiting, occurring in more than 30% of patients, indicating that while SG is effective, it also has notable adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer. Michaleas, S., Moreno Oliver, A., Mueller-Berghaus, J., et al.[2022]

In a phase 1/2 trial involving 108 patients with heavily pretreated metastatic triple-negative breast cancer, sacituzumab govitecan-hziy demonstrated a response rate of 33.3%, with a median duration of response of 7.7 months, indicating its efficacy in this challenging patient population.

The treatment was associated with significant myelotoxic effects, including anemia and neutropenia, but overall survival was promising at a median of 13.0 months, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. Bardia, A., Mayer, IA., Vahdat, LT., et al.[2019]

In a study of 43 patients with metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan, the median overall survival was 13.1 months, indicating its effectiveness in a real-world setting.

Common adverse events included alopecia, diarrhea, and neutropenia, with 27.9% of patients experiencing Grade 3 neutropenia, highlighting the need for careful management of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Reinisch, M., Bruzas, S., Spoenlein, J., et al.[2023]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and delivers a topoisomerase I inhibitor, showing promise in treating metastatic triple-negative breast cancer (mTNBC) after at least two prior therapies.

In April 2020, it received accelerated approval in the USA for mTNBC, and it is currently undergoing further clinical trials for various cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. Syed, YY.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Alpelisib: First Global Approval. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

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]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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]

6. United States pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. [2019]

10. England pubmed.ncbi.nlm.nih.gov

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]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. [2021]