TPS 99 Phase 3, Randomized, Open-Label TroFuse-010 Study of Sacituzumab Tirumotecan Alone and With Pembrolizumab Versus Treatment of Physician’s Choice Chemotherapy in Patients With HR+/HER2– Unresectable Locally Advanced or Metastatic Breast Cancer

TPS 99 Phase 3, Randomized, Open-Label TroFuse-010 Study of Sacituzumab Tirumotecan Alone and With Pembrolizumab Versus Treatment of Physician’s Choice Chemotherapy in Patients With HR+/HER2– Unresectable Locally Advanced or Metastatic Breast Cancer

Background

Additional therapies are needed to improve outcomes in patients with hormone receptor–positive/HER2-negative (HR+/HER2−) breast cancer that progressed on endocrine therapy (ET) plus CDK4/6 inhibitors (CDK4/6i). TROP2 is commonly overexpressed in patients with HR+/HER2− metastatic breast cancer and is associated with poor prognosis.Sacituzumab tirumotecan (sac-TMT; MK-2870/SKB264) is a novel anti-TROP2 antibody-drug conjugate composed of an anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker (average drug/antibody ratio, 7.4).In a phase 1/2 study, intravenous sac-TMT alone had antitumor activity in patients with previously treated HR+/HER2− metastatic breast cancer (ORR, 36.8%).TroFuse-010 evaluates sac-TMT alone or with pembrolizumab vs treatment of physician’s choice chemotherapy in patients with HR+/HER2− unresectable locally advanced or metastatic breast cancer who have not previously received chemotherapy.

Materials and Methods

This phase 3, randomized, open-label study (NCT06312176) is enrolling patients 18 years and older with HR+/HER2− unresectable locally advanced or metastatic breast cancer, ECOG performance status 0 to 1, and a tumor sample for central assessment of TROP2 expression and HR, HER2, and PD-L1 status. Patients are candidates for chemotherapy and had either (a) PD after 1 line or more of ET, 1 of which was with a CDK4/6i; (b) PD 6 months or less after starting first-line ET plus CDK4/6i, where the CDK4/6i was discontinued before the PD; (c) PD less than 6 months after starting first ET plus CDK4/6i where the CDK4/6i was discontinued before the PD and PD on an additional ET, either as monotherapy or with a PI3K or mTOR inhibitor; or (d) relapse during or 12 months or less after completing CDK4/6i given as adjuvant therapy with ET.Key exclusion criteria are prior chemotherapy in the metastatic setting and, if treated with prior (neo)adjuvant chemotherapy, recurrence 6 months or less after completion of chemotherapy. Patients are randomized 3:3:2 to intravenous sac-TMT 4 mg/kg every 2 weeks, intravenous sac-TMT 4 mg/kg every 2 weeks plus pembrolizumab 400 mg every 6 weeks, or physician’s choice chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, or liposomal doxorubicin) until radiographic PD, unacceptable toxicity, patient withdrawal, or discontinuation criteria are met. Randomization is stratified by PD-L1 combined positive score, TROP2 expression, and region. Primary end points are PFS per RECIST v1.1 by blinded independent central review (BICR) with sac-TMT vs physician’s choice chemotherapy and sac-TMT plus pembrolizumab vs physician’s choice chemotherapy. Secondary endpoints include OS, PFS per RECIST v1.1 by BICR with sac-TMT plus pembrolizumab vs sac-TMT, overall response rate, duration of response, patient-reported outcomes, and safety.

Status

Active recruitment is ongoing.