Alpelisib And Sacituzumab Govitecan For Treatment Of Breast Cancer

NCT05143229 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IIT-2021-ASSET
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

Brief Summary

This study evaluates the safety and efficacy of sacituzumab govitecan plus alpelisib for treatment of metastatic or locally recurrent HER2-negative breast cancer.

Conditions

Breast Cancer

Keywords

HER2-negative; Metastatic/locally advanced; Sacituzumab govitecan; Alpelisib; RP2D; Trop-2 antibody-drug conjugate; PI3K inhibitor

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose (RP2D) of alpelisib + sacituzumab govitecan

  Standard 3+3 dose escalation design (three dose levels of alpelisib plus sacituzumab govitecan) with dose-limiting toxicities (DLT) assessed during the first treatment cycle. If two or more of the six patients experienced a dose-limiting toxicity, dosing escalation would cease and maximum tolerated dose (MTD) would be reached. RP2D was the next lower dose at which \<1/6 subjects experienced a DLT.

  21 days

Secondary Outcomes (3)

• Pharmacokinetics of alpelisib when administered with sacituzumab govitecan

  In cycle 1, from prior to sacituzumab govitecan dosing through 48 hours after sacituzumab govitecan dosing

• Pharmacokinetics of sacituzumab govitecan when administered with alpelisib

  In cycle 1, from prior to sacituzumab govitecan dosing through 48 hours after sacituzumab govitecan dosing

• Overall response rate (ORR) in patients with measurable disease

  From start of study treatment until removal from study treatment; estimated 24 months maximum.

Study Arms (3)

Dose level 1: alpelisib 250 mg plus sacituzumab govitecan 8 mg/kg

EXPERIMENTAL

Alpelisib: 250 mg by mouth daily Sacituzumab govitecan: 8 mg/kg intravenous on days 1 and 8 of each 21 (+/-2) day cycle

Drug: Alpelisib; Drug: Sacituzumab govitecan

Dose level 2: alpelisib 250 mg plus sacituzumab govitecan 10 mg/kg

EXPERIMENTAL

Alpelisib: 250 mg by mouth daily Sacituzumab govitecan: 10 mg/kg intravenous on days 1 and 8 of each 21 (+/-2) day cycle

Drug: Alpelisib; Drug: Sacituzumab govitecan

Dose level 3: alpelisib 300 mg plus sacituzumab govitecan 10 mg/kg

EXPERIMENTAL

Alpelisib: 300 mg by mouth daily Sacituzumab govitecan: 10 mg/kg intravenous on days 1 and 8 of each 21 (+/-2) day cycle

Drug: Alpelisib; Drug: Sacituzumab govitecan

Interventions

Alpelisib DRUG

PI3K inhibitor

Also known as: Piqray

Dose level 1: alpelisib 250 mg plus sacituzumab govitecan 8 mg/kg; Dose level 2: alpelisib 250 mg plus sacituzumab govitecan 10 mg/kg; Dose level 3: alpelisib 300 mg plus sacituzumab govitecan 10 mg/kg

Sacituzumab govitecan DRUG

Trop-2-directed antibody and topoisomerase inhibitor drug conjugate

Also known as: Trodelvy

Dose level 1: alpelisib 250 mg plus sacituzumab govitecan 8 mg/kg; Dose level 2: alpelisib 250 mg plus sacituzumab govitecan 10 mg/kg; Dose level 3: alpelisib 300 mg plus sacituzumab govitecan 10 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• Males and females age ≥ 18 years
• ECOG Performance Status 0 - 2 (See Appendix A)
• Histologically proven HER2-negative breast cancer (per current ASCO-CAP guidelines); HER2-negative breast cancer includes hormone receptor-positive (estrogen receptor and/or progesterone receptor-positive) breast cancer and TNBC.
• HER2-negative breast cancer that at the time of study entry is either stage III (locally advanced) disease not amenable to curative therapy, or stage IV disease. Histological confirmation of recurrent/metastatic disease is encouraged but not required if clinical evidence of stage IV disease is available.
• Have measurable or evaluable disease.
• Ability to swallow and retain oral medicines.
• No limitations to number of prior chemotherapies or endocrine therapies for metastatic disease.
• All patients should have received at least one line of chemotherapy and at least one line of hormonal therapy (where appropriate) in either the advanced or neo/adjuvant setting. Patients who are candidates for anti-PD-1 and/or anti-PD-L1 therapy should have received at least one line of anti-PD-1 and/or anti-PD-L1 therapy in either the advanced or neo/adjuvant setting.
• Prior palliative radiation therapy to bony metastases is allowed. A minimum of 14 days between the end of radiation treatment and start of study treatment is required.
• Participants with previously treated brain metastases must be free of central nervous system symptoms and be \>21 days from treatment of brain metastases. CNS brain metastasis should be clinically stable at the time of screening, and participant is not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases.
• Participants must be \>2 weeks or 5 half-lives (whichever is longer) from prior systemic chemotherapy for breast cancer AND should have recovered to Grade 1 or better (except alopecia and neuropathy) from related side effects of any prior antineoplastic therapy prior to study entry.
• Women of childbearing potential must have a negative serum pregnancy test 24 hours prior to initiating treatment.
• Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use approved forms of contraception for the duration of study participation and for 6 months following completion of therapy.
• Fasting plasma glucose ≤140 mg/dL or ≤7.8 mmol/L

You may not qualify if:

• Simultaneously enrolled in any therapeutic clinical trial
• Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study
• Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
• Is pregnant or breastfeeding
• Has a known allergic reaction to any excipient contained in the study drug formulation Active Grade 3 (per the NCI CTCAE, Version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment.
• Patient has previously been treated with sacituzumab govitecan or alpelisib.
• Patient has a concurrent malignancy or malignancy within 3 years of study enrollment (with the exception of adequately treated basal or squamous cell carcinoma, non-melanomatous skin cancer, or curatively resected cervical cancer).
• Diabetes mellitus type I, or uncontrolled type II based on fasting plasma glucose and HbA1c meeting either of the following:
• Fasting plasma glucose \>140 mg/dL or \>7.8 mmol/L
• HbA1c ≥6.5% Note: For patients with fasting plasma glucose ≥ 100 mg/dL and/or HbA1c ≥5.7% (i.e. threshold for pre-diabetes) at baseline, lifestyle changes according to American Diabetes Association guidelines were recommended
• Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
• Patient is classified into Child-Pugh class B or C.
• Patient has a known history of HIV infection (testing not mandatory).
• Patient has active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). In patients with a history of HBV or HCV, patients with a detectable viral load will be excluded.
• Patient has symptomatic/untreated CNS disease.

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• Novartis Pharmaceuticals: collaborator
• Gilead Sciences: collaborator

Study Sites (7)

The University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

The University of Kansas Cancer Center - Overland Park

Overland Park, Kansas, 66210, United States

Location

The University of Kansas Cancer Center - Indian Creek

Overland Park, Kansas, 66211, United States

Location

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

The University of Kansas Cancer Center - North Kansas City Hospital

Kansas City, Missouri, 64116, United States

Location

The University of Kansas Cancer Center - North

Kansas City, Missouri, 64154, United States

Location

The University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Alpelisib; sacituzumab govitecan

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Priyanka Sharma, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Standard 3+3 dose escalation

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: December 3, 2021
• Study Start: March 28, 2022
• Primary Completion: January 28, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

US (7)