A Phase Ib, multicenter, open-label dose escalation and expansion platform study of select immunotherapy combinations in adult patients with triple negative breast cancer
- Conditions
- Triple negative breastcancer10006291
- Registration Number
- NL-OMON49712
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 4
ECOG Performance Status * 1
Patients with advanced/metastatic TNBC with measurable disease as determined by
RECIST version 1.1
Documented disease progression or intolerance to no more than 2 prior lines of
chemotherapy for advanced disease. Prior treatment with targeted agents or
checkpoint inhibitors will not count as a line of prior therapy unless
chemotherapy was administered concurrently.
Patients must have received prior systemic treatment that included taxane-based
chemotherapy for neoadjuvant or metastatic disease.
Patients must have a site of disease amenable to core needle biopsy, and be a
candidate for tumor biopsy according to the treating institution*s guidelines.
Patients must be willing to undergo a new tumor biopsy at screening, and during
therapy on the study.
See for more details protocol section 5.1
Dose expansion arm(s), checkpoint- inhibitor-naive group only: Prior checkpoint
inhibitor therapy.
Presence of symptomatic central nervous system (CNS) metastases, or CNS
metastases that require local CNS-directed therapy (such as radiotherapy or
surgery), or increasing doses of corticosteroids within 2 weeks prior to
initiating study treatment.
Patients with treated brain metastases should be neurologically stable for at
least 4 weeks prior to study entry and off steroids for at least 2 weeks before
administration of any study treatment.
Out of range laboratory values:
- Creatinine clearance < 40 mL/min
- Total bilirubin > 1.5 x ULN, except for patients with Gilbert*s syndrome if
total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
- ALT and AST > 3 x ULN
- Absolute neutrophil count < 1.0 x 109/L
- Platelet count < 75 x 109/L
- Hemoglobin < 9 g/dL
- Potassium, magnesium, calcium or phosphate abnormality > CTCAE grade 1
despite appropriate replacement therapy
Impaired cardiac function or clinically significant cardiac disease
Cardiac Troponin T (cTnT) or Cardiac Troponin I (cTnI) elevation > Grade 1
History or current diagnosis of myocarditis.
Subjects assigned to the canakinumab arm are required to be tested using
Interferon-* release assay.
For patients assigned to the the MCS110 arm, active tuberculosis requiring
systemic antibiotic
therapy is excluded.
Other exclusion criteria may apply (see protocol section 5.2)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Incidence and severity of AE*s and SAE*s. DLTs (incidence and nature), dose<br /><br>interruptions/reductions.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Serum/plasma concentrations and PK parameters of individual investigational<br /><br>drugs within combination treatments<br /><br>Presence and/or concentration of anti-drug antibodies<br /><br>Best overall response (BOR) and PFS per RECIST v1.1 and iRECIST<br /><br>Changes from baseline of PD markers in tumor tissue (e.g.TILs, CD8, PD-L1,<br /><br>LAG-3 </p><br>