This is a Phase II trial to assess efficacy and feasibility of pembrolizumab + INBRX-106 as an induction therapy preceding neoadjuvant therapy.
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.
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.
Single group
Pembrolizumab
DrugDrug will be delivered per standard-of-care as established by trial Keynote-522.
INBRX-106
DrugINBRX-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.
Volumetric Response
Patients achieving (\>30%) reduction in ultrasound estimate of breast mass volume (mL) at the end of 2 cycles investigational therapy
Pathological response (following extended INBRX-106 + pembrolizumab)
Patients achieving pathological response after completion of study therapy followed by additional neoadjuvant therapy per treating physician discretion, ascertained at the time of definitive surgery.
Pathological response (post-chemotherapy)
Number of patients achieving pathological response following extended anti-OX40 + pembrolizumab if continued beyond 2 cycles (option 2).
IO-path response assessed prior to Cycle 2
On study biopsy conducted prior to Cycle 2: * IO-path-NE (not evaluable): no tumor or evidence of treatment effect. * IO-path-NR (no response): tumor present, no appreciable treatment effect, no sTILs/iTILs expansion by at least 10% absolute increase from baseline. * IO-path-PR (partial response): tumor present, +treatment effect and/or sTILs/iTILs expansion by at least 10% absolute increase from baseline. * IO-path-CR (complete response): no viable tumor, + treatment effect.
Event free survival
Date of dose 1 until evidence of cancer recurrence or death. Those alive without recurrence are censored at 5 years after the last dose of study drug.
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Providence Health & Services
Lead sponsor
Inhibrx Biosciences, Inc
Collaborator
