This is an open-label, phase Ib/II study of neratinib plus Capmatinib in patients with metastatic breast cancer and metastatic IBC.~Phase 1b - Dose Escalation of Neratinib with Capmatinib This phase of the study will employ the Bayesian optimal interval (BOIN) design with the 3+3 design run-in, to find the MTD. The BOIN design is implemented in a simple way similar to the traditional 3+3 design, but is more flexible and possesses superior operating characteristics that are comparable to those of the more complex model-based designs, such as the continual reassessment method (CRM). The maximum sample size for dose escalation is 27. Patients are treated in cohorts of 3, beginning with Neratinib PO dose level 1 (120 mg, Days 1-7, 160 mg, through end of treatment, see Table 2) in combination with Capmatinib PO level 1 (400 mg, see Table 3), with a maximum of 12 patients per dose. The target toxicity rate for the maximum tolerable dose (MTD) is 25%.~Phase II Phase II will be a prospective, open label, interventional study with previously treated HER2-negative metastatic breast cancer and metastatic inflammatory breast cancer patients. Subjects receive Capmatinib in combination with neratinib. The MTD determined during Phase 1b will be used.~This portion of the trial will be conducted to assess the overall response rate (ORR) for patients treated at the MTD. The target ORR will be 25%, with unacceptable ORR as 5%. We assess the ORR using the Bayesian optimal phase 2 (BOP2) design (Zhou, Lee and Yuan, 2017).~Up to an additional 29 evaluable subjects with measurable disease will be enrolled. An interim analysis will be performed when the number of enrolled patients reaches 15.
This study is to learn if the combination therapy of capmatinib and neritinib can help to control metastatic or locally advanced breast cancer. Researchers also want to find the highest tolerable dose of the combination therapy of capmatinib and neritinib that can be used in this study drug combinations. The safety of this drug combination and the CELsignia MP test methodology will also be studied.