Neoadjuvant INBRX-106 in Combination With Pembrolizumab for Stage II/III TNBC Patients

NCT06353997 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 2024000099
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase II trial to assess efficacy and feasibility of pembrolizumab + INBRX-106 as an induction therapy preceding neoadjuvant therapy.

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Volumetric Response

  Patients achieving (\>30%) reduction in ultrasound estimate of breast mass volume (mL) at the end of 2 cycles investigational therapy

  At the end of Cycle 2 (each cycle is 21 days)

Secondary Outcomes (6)

• Pathological response (following extended INBRX-106 + pembrolizumab)

  30 days from last dose of study treatment

• Pathological response (post-chemotherapy)

  30 days from last dose of study treatment

• IO-path response assessed prior to Cycle 2

  Day 21

• Event free survival

  Up to 2 years

• Overall survival

  Up to 2 years

Study Arms (1)

Pembrolizumab + INBRX-106

EXPERIMENTAL

Patients will be given pembrolizumab at a dose of 200mg IV in combination with INBRX-106 at a dose of 0.1mg/kg IV every 3 weeks.

Drug: Pembrolizumab; Drug: INBRX-106

Interventions

Pembrolizumab DRUG

Drug will be delivered per standard-of-care as established by trial Keynote-522.

Also known as: KEYTRUDA

Pembrolizumab + INBRX-106

INBRX-106 DRUG

INBRX-106 is a hexavalent, recombinant humanized IgG1, OX40 agonist antibody that targets the human OX40 receptor (TNFRSF4, UniProtKB: P43489). INBRX-106 is based on a sdAb platform and, in detail, 3 identical humanized camelid heavy chain-only antibody binding domains (VHHs) targeting OX40 are joined end-to-end and with an Fc based on human IgG1 to create a molecule that homo-dimerizes into an antibody targeting a total of 6 OX40 receptors.

Pembrolizumab + INBRX-106

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, inclusive of all genders.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 2.
• Patients must have histologically confirmed TNBC (ER/PR ≤ 10% allowed, HER2- as defined by ASCO guidelines). HER2 negative permitted to enroll as IHC 0, 1, or 2+ with negative ISH.
• Primary breast tumor measurable by ultrasound and at least 1cm.
• Clinically appropriate to receive neoadjuvant pembrolizumab plus chemotherapy (e.g. Keynote-522) planned for curative intent per standard of care (as indicated following study therapy however not mandated on trial for Option 2).
• Multifocal/multicentric disease is allowed. If clinically indicated per the standard of care, suspicious sites that do not appear to be part of the same disease process should be biopsied with reconfirmation of ER/PR/HER2 status. Up to 20 slides or 1 block may be submitted to conduct biomarkers studies on remaining tissue.
• No prior therapy of any kind for TNBC.
• Willingness to undergo serial ultrasounds, serial biopsies, and blood draws.
• Patients must have adequate organ function as defined below. Specimens must be collected within 28 days prior to the start of study treatment.
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100 000/µL
• Hemoglobin ≥8.0 g/dL or ≥5.0 mmol/L
• Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
• Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN. Patients with elevated LFTs that are suggestive of Gilbert's disease (a benign process) are eligible.
• AST (SGOT) and ALT (SGPT) ≤2.5 × ULN

You may not qualify if:

• Bilateral breast cancer.
• Prior malignancies that require ongoing active therapy or are at clinically significant risk of systemic recurrence in the opinion of the investigator.
• Suspicion for, or histologically confirmed, metastatic disease.
• Primary tumor with potential for skin ulceration or invasion of the chest wall, or with pain that would suggest rapid progression or imminent muscle/skin involvement in the opinion of the enrolling investigator.
• Prior therapy with an anti-PD-1, anti-PD-L1, or antiPDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, CD137). Patients who have received these agents more than 3 years prior for other malignancies may be considered if they are not still at clinically significant risk of systemic recurrence in the opinion of the investigator.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Additionally, COVID-19 vaccinations (including boosters) should not be scheduled within 72 hours (before or after) of dosing days for INBRX-106 and pembrolizumab.
• Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Pregnant or breastfeeding.
• History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• History of allogenic tissue/solid organ transplantation.
• Has active autoimmune disease that has required systemic treatment in excess of prednisone 10mg daily or equivalent in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Has a known additional malignancy (other than their current breast cancer diagnosis) that is progressing or has required active systemic treatment within the past 3 years.

Sponsors & Collaborators

• Providence Health & Services: lead
• Inhibrx Biosciences, Inc: collaborator

Study Sites (4)

Ellison Institute of Technology (EITM)

Los Angeles, California, 90064, United States

RECRUITING

Providence Portland Cancer Institute - Franz Clinic

Portland, Oregon, 97213, United States

RECRUITING

Providence St. Vincent Medical Center

Portland, Oregon, 97225, United States

RECRUITING

Swedish Cancer Institute

Seattle, Washington, 98104, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• David Page, MD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicole Moxon, RN

CONTACT

503-215-1979; canrsrchstudies@providence.org

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: March 26, 2024
• First Posted: April 9, 2024
• Study Start: September 5, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2029
• Last Updated: January 15, 2026

Record last verified: 2026-01

Locations

US (4)