Dr Isakoff on Data for Invikafusp Alfa Plus Sacituzumab Govitecan in Advanced HR+ or Triple-Negative Breast Cancer

An important correlative goal was to confirm that the activity that we’ve seen with [invikafusp alfa] as a single agent is preserved in this combination study, and in terms of clinical activity, what we’ll be reporting is that in both cohorts, we’ve seen activity.

Steven Isakoff, MD, PhD, MMSc, an associate physician in the Division of Hematology and Medical Oncology at Massachusetts General Hospital, associate director for clinical research at the Mass General Cancer Center, director of the Triple-Negative Breast Cancer (TNBC) Program and the Mass General Scalp Cooling Program, and an assistant professor of medicine at Harvard Medical School, discussed interim data from the phase 1b/2 STARt-002 trial (NCT06827613) evaluating the dual T-cell agonist invikafusp alfa (STAR0602) plus sacituzumab govitecan-hziy (Trodelvy) in metastatic TNBC or hormone receptor (HR)–positive, HER2-negative metastatic breast cancer.

Data were presented at the 2026 SITC Annual Meeting. As of the October 16, 2026, data cutoff, 48 patients had enrolled, including 38 who were evaluable for efficacy.

The study aimed to determine the safety, feasibility, and tolerability of the combination and to gauge preliminary activity, Isakoff explained. Correlative analyses showed selective Vβ6-positive T-cell expansion in all 8 patients examined during cycle 1, consistent with invikafusp alfa monotherapy in the phase 1/2 STARt-001 trial (NCT05592626).

Although the single-arm study was not designed to rigorously assess efficacy, responses occurred in both cohorts, Isakoff noted. The objective response rate (ORR), which included unconfirmed responses, was 28% in the TNBC cohort (n = 18) and 25% in the HR-positive/HER2-negative cohort (n = 20), with disease control rates of 67% and 80%, respectively. In patients without prior topoisomerase I inhibitor–based antibody-drug conjugate exposure, ORRs were 36% (n = 14) and 27% (n = 15), respectively. Responses included a complete response (CR) ongoing beyond 12 months in a patient with TNBC and a CR in a patient with HR-positive/HER2-negative disease after prior fam-trastuzumab deruxtecan-nxki (Enhertu).

Because the agents have nonoverlapping toxicities, the known adverse effects (AEs) of each were observed, with no new or unexpected toxicities, Isakoff said. Overall (n = 48), the most common treatment-related AEs associated with sacituzumab govitecan were decreased neutrophil count (68.8%; grade 3/4, 58.3%) and diarrhea (62.5%; grade 3, 20.8%), which were managed with standard medications, he noted. Cytokine release syndrome, the main toxicity of invikafusp alfa, occurred in 85.4% of patients and was mostly grade 1 or 2 (grade 3, 16.7%), mirroring the monotherapy experience, he concluded. No treatment-related deaths occurred.