514 Initial clinical results from START-002: a phase 1b/2 study of invikafusp alfa, a first-in-class dual T-cell agonist, in combination with sacituzumab govitecan in triple-negative or HR + /HER2 - mBC
Year: 2026
Type: conference-abstract
Abstract: Background Invikafusp alfa (invika), a first-in-class dual T-cell agonist, has demonstrated monotherapy clinical responses across multiple TMB-H solid tumor types including triple-negative breast cancer (TNBC). Sacituzumab govitecan (SG), a TROP-2–directed antibody–drug conjugate (ADC), is approved for mTNBC and HR +/HER2- mBC. START-002 evaluates the hypothesis that combining the immunomodulatory potential of SG with invika-mediated selective activation and expansion of tumor-reactive Vβ6/Vβ10 T-cells will enhance anti-tumor activity.Methods START-002 is a Ph 1b/2 study evaluating invika in combination with SG in 2L+ mTNBC or 3L+ HR +/HER2- mBC. Patients may have received prior CPI and/or ADC. The Ph 1b safety run-in evaluated feasibility and safety followed by separate Ph2 expansion cohorts.Results Among 22 evaluable heavily pre-treated (median 4 prior lines) patients without prior SG, the ORR is 33% in HR +/HER2- (4/12) and 30% in mTNBC (3/10). In mTNBC patients with PD-L1 CPS < 10, the ORR is 60% (3/5). Confirmed complete responses were observed in both tumor subtypes, along with 5 partial responses (3 HR+/HER2-, 2 TNBC) (figure 1). The disease control rate is 82% (18/22), with clinical benefit persisting >24 weeks in 6 patients. Notably, antitumor activity has been observed in patients with chest wall or skin disease, including a patient with mTNBC who achieved a durable complete response of a 10-cm breast skin lesion, and another mTNBC patient with complete resolution of a 3-cm chest wall lesion.Among 41 patients (18 mTNBC and 23 HR+/HER2- mBC) treated, the combination safety of invika + SG was consistent with the known toxicities of each agent. The most common treatment related adverse events (TRAE) associated with SG included: diarrhea (44% grade 1-2, 20% gr3-4), neutropenia (5% gr 1-2, 54% gr3-4), fatigue (41% gr 1-2, 12% gr3-4), and nausea (37% gr 1-2, 5% gr3-4). The most common TRAEs associated with invika were low grade and included: cytokine release syndrome (68% gr 1-2, 7% grade 3, no gr 4), rash (34% gr 1-2, 7% gr 3-4), and fatigue (22% gr 1-2, 12% gr 3-4).Dose-dependent increases in Cmax/ AUC and selective TRBV6 expansion similar to monotherapy invika were observed. Additional translational analyses to further understand the mechanisms of response are currently being performed.Conclusions This first-in-human study demonstrates encouraging preliminary clinical activity of invika in combination with SG, including confirmed complete responses and durable clinical benefit in both TNBC and HR +/HER2- disease, with manageable safety in heavily pre-treated patients. These data support continued clinical development of this novel combination.Abstract 514 Figure 1 Waterfall plot: best target lesion response
Institutions: Massachusetts General Hospital, USC Norris Comprehensive Cancer Center, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, BC Cancer Agency, Princess Margaret Cancer Centre, UCLA Health, UCLA Jonsson Comprehensive Cancer Center, The University of Texas at San Antonio Health Science Center, Sarah Cannon
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225345271