Combination Liposomal Irinotecan and Pembrolizumab For Triple-Negative Breast Cancer (TNBC) With Brain Metastases (BM)

NCT05255666 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 202111198
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study is a phase II with safety lead in, single arm, study using Nal-IRI in combination with pembrolizumab. Nal-IRI will be given IV every 2 weeks starting at 50mg/m2. Pembrolizumab will be given 400mg IV every 6 weeks. Treatment will continue until progression, intolerable side effects or patient/doctor decision to discontinue treatment.

Conditions

Triple Negative Breast Cancer; Brain Metastases

Outcome Measures

Primary Outcomes (1)

• Central Nervous System Disease Control Rate (DCR)

  -DCR is defined as the rate of complete response (CR) + rate of partial response (PR), and rate of stable disease (SD) at 6 months and will be determined as per modified Neuro-Oncology-Brain Metastases (RANO-BM) criteria

  6 months

Secondary Outcomes (5)

• Safety and tolerability as measured by the number of grade 3 and 4 adverse events

  Through 90 days after completion of treatment (estimated to be 9 months)

• Central Nervous System Objective Response Rate (ORR)

  Through completion of treatment (estimated to be 6 months)

• Non-Central Nervous System Objective Response Rate (ORR)

  Through completion of treatment (estimated to be 6 months)

• Progression Free Survival (PFS)

  Through completion of follow-up (estimated to be 3 years and 6 months)

• Overall Survival (OS)

  Through completion of follow-up (estimated to be 3 years and 6 months)

Study Arms (1)

Pembrolizumab + Liposomal Irinotecan

EXPERIMENTAL

* 400 mg of pembrolizumab intravenously on Day 1 of each Cycle (Cycle is 42 days) * 50 mg/m\^2 of liposomal irinotecan (Nal-IRI) intravenously every 2 weeks of each Cycle (Cycle is 42 days)

Drug: Pembrolizumab; Drug: Liposomal Irinotecan

Interventions

Pembrolizumab DRUG

400 mg intravenously

Also known as: Keytruda

Pembrolizumab + Liposomal Irinotecan

Liposomal Irinotecan DRUG

Starting at 50 mg/m\^2. The dose may be increased to 70 mg/m\^2 if tolerated or dose reduced to 35 mg/m\^ if treatment-emergent severe adverse event (TESAE) occurs.

Also known as: NaI-IRI

Pembrolizumab + Liposomal Irinotecan

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-1 within 28 days prior to registration.
• Histological or cytological confirmation of triple-negative breast cancer (TNBC) NOTE: TNBC will be defined as expression of ER\<10%, PR\< 10% and HER2 negative either by IHC (0, 1+ are negative, 2+ equivocal) or in situ hybridization method (ratio \<2.0 is negative). AJCC, 8th edition.
• Subjects must have brain metastasis; new or progressive with at least one lesion ≥ 5 mm in at least one dimension. NOTE: the number of brain lesions is not limited.
• Measurable disease according to RECIST 1.1 and/or RANO-BM within 28 days prior to registration.
• Prior treatment with immunotherapy is allowed. Patients CANNOT have received prior liposomal irinotecan or irinotecan. Patients who received prior sacituzumab govitecan are eligible if without disease progression for at least 16 weeks on therapy and a washout of at least 24 weeks prior to C1D1. NOTE: No more than 4 prior lines of therapy in the metastatic setting is allowed.
• Prior cancer treatment including investigational agents must be completed at least 14 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline.
• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 14 days prior to registration.
• Hematological
• Absolute Neutrophil Count (ANC): ≥ 1.5 K/mm3
• Hemoglobin (Hgb): ≥ 9 g/dL; without erythropoietin dependency and without packed red blood cell (PRBC) transfusion within 2 weeks of registration
• Platelet Count (PLT): ≥100 000/µL
• Renal
• Creatinine OR: ≤1.5 × ULN OR

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Has a known history of Human Immunodeficiency Virus (HIV) infection. NOTE: No HIV testing is required unless mandated by local health authority.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. NOTE: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
• Has a known history of active TB (Bacillus Tuberculosis).
• Has an active infection requiring systemic therapy.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has received colony-stimulating factors (e.g., granulocyte colony stimulating factor \[G-CSF\], granulocyte macrophage colony stimulating factor \[GM-CSF\]) within 2 weeks prior to the first dose of study drug.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to C1D1.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• Has had an allogenic tissue/solid organ transplant.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Is pregnant or breastfeeding.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Merck Sharp & Dohme LLC: collaborator
• Ipsen: collaborator

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Brain Neoplasms

Interventions

pembrolizumab; irinotecan sucrosofate

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Ashley Frith, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2022
• First Posted: February 24, 2022
• Study Start: July 31, 2023
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2030
• Last Updated: July 11, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share