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

A Simon 2-stage design is implemented to minimize exposure if the treatment regimen is not feasible or if no response. If feasibility is established with responses exceeding futility parameters, study will expand to stage 2. Additional arms may be introduced in a protocol amendment. Below shows the sample size required using Simon's 2-stage design, 80% power and 5% one-sided significance level: * Null hypothesis: \<5% week 6 US response * Alternative hypothesis: \>35% week 6 US response * Stage I n (r\*): 6 (0) * Stage I + II total n (r): 12 (2) * Criteria: Minimax * Minimum responses to proceed to stage II: 1 Note: r\* and r represents the threshold for declaring futility, i.e. greater than r\* or r responses would be required to consider ongoing investigation. The null hypothesis of 5% is based upon the assumption that virtually no subjects would experience volumetric reduction if the therapy was not effective. The alternative hypothesis of 35% is based upon the assumption that responses in the absence of chemotherapy in approximately one-third of subjects would be clinically meaningful, encouraging further development of the treatment paradigm. If no responses are observed, a second feasibility run-in may be considered using a biomarker enrichment strategy (such as with the 27-gene IO score). The arm will be terminated from further development if an unacceptable proportion of patients experience rapid clinical/radiographic progression (defined as progression of disease, or clinical evidence of progression), or other toxicities that interfere with curative-intent therapy, defined as \>1/6 evaluable subjects in stage I or \>2/12 in stage II, evaluated for each arm. This is a Pocock-type stopping boundary that yields the probability of cross the boundary at most 23% when the rate of dose-limiting toxicity is equal to 10%.