Zotatifin And EIF4A Platinum Helix Inhibition In Resistant AdvancedTNBC

NCT07783659 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2026-0091NCI-2026-06281
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

To find the optimal (best) recommended dose of zotatifin and carboplatin to treat patients with metastatic or recurrent TNBC.

Conditions

Phase IB; Zotatifin; EIF4A; Advanced TNBC; Platinum Helix Inhibition

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs).

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (1)

ZOT-CAR: Phase 1b Treatment with Zotatifin + Carboplatin

EXPERIMENTAL

Drug: Zotatifin; Drug: carboplatin

Interventions

Zotatifin DRUG

Given by IV

ZOT-CAR: Phase 1b Treatment with Zotatifin + Carboplatin

carboplatin DRUG

Given by IV

ZOT-CAR: Phase 1b Treatment with Zotatifin + Carboplatin

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed malignancy that is metastatic or locally recurrent unresectable and for which standard curative or palliative measures do not exist or are no longer effective.
• Participants must have histologically or cytologically confirmed non-IBC triple negative breast cancers, defined here as ER\<1%, PR\<1% and HER2 negative per ASCO CAP 2018 guideline and have received at least 2 lines of therapy during metastatic treatment, OR Inflammatory breast cancer (IBC) clinically confirmed (³25) and that is ER\<10% and PR\<10% without limits of previous line of therapy.
• At least 1 week since prior chemotherapy or radiation therapy. At least 2 weeks since prior use of strong or moderate inhibitors or inducers of CYP3A4.
• Age ≥18 years.
• Has at least one measurable lesion per RECIST 1.1
• ECOG performance status ≤ 2 (Karnofsky ≥ 60%,).
• Participants must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥ 1,000/mcL
• hemoglobin \>9 mg/dL
• platelets ≥ 100,000/mcL
• total bilirubin ≤ institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN; ≤ 5 × institutional ULN if confirmed liver metastasis and elevation is deemed to be directly due to metastasis.
• Creatinine clearance ≥30 mL/min (measured by the Cockcroft-Gault equation\*).
• Ability to understand and the willingness to sign a written informed consent
• Cognitively impaired subjects will not be enrolled in this study.

You may not qualify if:

• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) except for alopecia. Note: Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to \> Grade 2 for at least 3 months prior to \[enrollment/Cycle 1 Day 1\] and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, including: Chemotherapy-induced neuropathy, Fatigue, Residual toxicities from prior IO treatment: Grade 1 or Grade 2 endocrinopathies which may include: Hypothyroidism/hyperthyroidism, Type I diabetes, Hyperglycemia, Adrenal insufficiency, Adrenalitis and Skin hypopigmentation (vitiligo)
• Participants with a history of interstitial lung disease (past or current) or active, non-infectious pneumonitis.
• Participants with active autoimmune disease requiring systemic immunosuppression with corticosteroids (\> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within 2 years before the first dose of study treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to carboplatin or zotatifin.
• Participants with uncontrolled intercurrent illness. Medical history or complication considered inappropriate for participation in the study, or a serious physical or psychiatric disease, the risk of which may be increased by participation in the study in the investigator's opinion
• Participants with active infections requiring systemic antibiotics or antifungal or antiviral treatment within 14 days of C1D1 study treatment.
• Participants with known active Hepatitis B or Hepatitis C infection. Testing is required to establish eligibility. Active Hepatitis B infection is defined as a positive Hepatitis B surface antigen and positive Hepatitis B core antibody test. Active Hepatitis C infection is defined as a quantitative HCV-RNA test with results greater than the lower limit of detection of the assay.
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Participant s with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Participant s with known HIV infection, defined as positive for HIV1/2 antibodies. Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• Participant s with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study due to potential for teratogenic or abortifacient effects.
• Participant s with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Participant s with active brain metastasis if treatment is warranted. Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
• Participant s with known leptomeningeal disease, defined as unequivocal imaging or cytology-proven disease.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Cancer Prevention Research Institute of Texas: collaborator
• SJP Biotec: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Interventions

Carboplatin

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Bora Lim, MD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bora Lim, MD

CONTACT

713-745-0689; BLim@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: August 21, 2026
• First Posted: August 25, 2026
• Study Start (Estimated): February 12, 2027
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2032
• Last Updated: August 25, 2026

Record last verified: 2026-08

Locations

US (1)