NCT05243641

Neratinib and Capmatinib Combination (Phase Ib/II) in Metastatic Breast Cancer and Inflammatory Breast Cancer Patients With Abnormal HER-family and c-Met Pathway Activity as Measured by the CELsignia Signaling Analysis Test

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

This is an open-label, phase Ib/II study of neratinib plus Capmatinib in patients with metastatic breast cancer and patients with 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 18. Patients are treated in cohorts of 3, beginning with Neratinib PO dose level 1 (120 mg, Dose 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 for patients with previously treated HER2-negative metastatic breast cancer or metastatic inflammatory breast cancer. Subjects receive Capmatinib in combination with Neratinib (including an AI for patients with ER+/HER2- breast cancer). 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.

Conditions

• Metastatic Breast Cancer
• Breast Cancer

Interventions

Type	Name	Description
DRUG	Neratinib	Nertatinib will be supplied as 40 mg tablets, equivalent to 48.31 mg neratinib maleate.
DRUG	Capmatinib	Capmatinib will be supplied at 200 mg and 150 mg tablets

Timeline

• Start date: 2022-08-18
• Primary completion: 2024-11-19
• Completion: 2024-11-19
• First posted: 2022-02-17
• Last updated: 2025-06-11
• Results posted: 2025-05-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study