A Study of Sacituzumab With Chemoimmunotherapy to Treat Advanced Triple-Negative Breast Cancer After Prior Therapies

NCT04927884 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: QUILT-3.058
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1b/2 open-label study to evaluate the safety and efficacy of sacituzumab govitecan-hziy in combination with chemoimmunotherapy (cyclophosphamide, N-803, and PD-L1 t-haNK) in subjects with Triple Negative Breast Cancer (TNBC) after at least 2 prior treatments for metastatic disease.

Conditions

Advanced Triple Negative Breast Cancer

Keywords

Chemoimmunotherapy; Stage IV TNBC; Sacituzumab; N-803; PD-L1 t-haNK; Cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events

  30 days after last dose, up to 65 weeks and 5 days

Study Arms (1)

All subjects

EXPERIMENTAL

Sacituzumab plus chemoimmunotherapy (cyclophosphamide, N-803, and PD-L1 t-haNK)

Biological: N-803; Biological: PD-L1 t-haNK; Drug: Sacituzumab Govitecan-Hziy; Drug: Cyclophosphamide

Interventions

N-803 BIOLOGICAL

Dose: 15 μg/kg subcutaneously (SC) Frequency: administered on Day 8 of each cycle (every 3 weeks)

All subjects

PD-L1 t-haNK BIOLOGICAL

Dose: \~2 × 10\^9 cells intravenously (IV) Frequency: administered on Days 1 and 8 of each cycle (every 3 weeks)

All subjects

Sacituzumab Govitecan-Hziy DRUG

Phase 1b: Dose level 1: Sacituzumab govitecan-hziy (7.5 mg/kg IV) Dose level 2: Sacituzumab govitecan-hziy (10 mg/kg IV) Dose level -1 (if needed): Sacituzumab govitecan-hziy (5.0 mg/kg IV) Phase 2: Dose based on Phase 1b Recommended Phase 2 Dose (IV) Frequency: administered on Days 1 and 8 of each cycle (every 3 weeks)

All subjects

Cyclophosphamide DRUG

Dose: 25 mg capsules taken twice per day by mouth (PO) Frequency: to be taken Days 1-15 and 15-19 of each cycle (every 3 weeks)

All subjects

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or Independent Ethics Committee (IEC) guidelines.
• Histologically confirmed stage IV TNBC. Subjects must have had at least 2 prior treatments for TNBC. TNBC is defined as breast cancer that lacks estrogen receptor (ER) and progesterone receptor (PgR) expression (both ≤ 1% of tumor cell nuclei), and human epidermal growth factor receptor 2 (HER2) overexpression and/or amplification (IHC 0 or 1+, or IHC 2+ and fluorescence in situ hybridization \[FISH\]-), according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline criteria, as evaluated by local institutions.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
• Have at least 1 measurable lesion of ≥ 1.0 cm and/or non-measurable disease evaluable in accordance with RECIST V1.1.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• Agreement to practice effective contraception for female subjects of child-bearing potential and non-sterile males. Female subjects of child-bearing potential must agree to use effective contraception while on study and for at least 5 months after the last dose of study treatment. Non-sterile male subjects must agree to use a condom while on study and for up to 5 months after the last dose of study treatment. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide, intrauterine devices (IUDs), oral contraceptives, and abstinence.

You may not qualify if:

• Have previously received or are currently receiving treatment with sacituzumab govitecan-hziy.
• Serious uncontrolled concomitant disease that would contraindicate the use of the investigational drug used in this study or that would put the subject at high risk for treatment-related complications.
• Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma).
• History of organ transplant requiring immunosuppression.
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Inadequate organ function, evidenced by the following laboratory results:
• Absolute neutrophil count (ANC) \< 1500 cells/mm3.
• Platelet count \< 75,000 cells/mm3.
• Hemoglobin \< 9 g/dL.
• Total bilirubin greater than the upper limit of normal (ULN; unless the subject has documented Gilbert's syndrome).
• Aspartate aminotransferase (AST \[SGOT\]) or alanine aminotransferase (ALT \[SGPT\]) \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases).
• Alkaline phosphatase (ALP) levels \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases, or \>10 × ULN in subjects with bone metastases).
• Serum creatinine \> 2.0 mg/dL or 177 μmol/L.
• Uncontrolled hypertension (systolic \> 160 mm Hg and/or diastolic \> 110 mm Hg) or clinically significant (ie, active) cardiovascular disease, cerebrovascular accident/stroke, or myocardial infarction within 6 months prior to first study medication; unstable angina; congestive heart failure of New York Heart Association grade 2 or higher; or serious cardiac arrhythmia requiring medication.
• Current chronic daily treatment (continuous for \> 3 months) with systemic corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have known contrast allergies is allowed.

Sponsors & Collaborators

• ImmunityBio, Inc.: lead

Study Sites (1)

Hoag Memorial Hospital

Newport Beach, California, 92663, United States

Location

MeSH Terms

Interventions

ALT-803; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

The study was terminated early due to low enrollment. Only the safety data is provided.

Results Point of Contact

• Title: Chaitali Nangia, MD Oncologist
• Organization: CSSIFM

Chaitali.nangia@cssifm.org

855-797-9277

Study Officials

• Bobby Reddy, MD

  ImmunityBio, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: June 16, 2021
• Study Start: September 8, 2021
• Primary Completion: September 13, 2022
• Study Completion: December 12, 2022
• Last Updated: June 12, 2024
• Results First Posted: June 12, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)