Antibody-Based Cancer Therapies Show Promise in Breast Cancer, Imaging, and Lymphoma

The combination of sacituzumab govitecan-hziy (Trodelvy) and pembrolizumab (Keytruda) significantly improved progression-free survival compared with chemotherapy plus pembrolizumab as a frontline treatment for patients with PD-L1–positive, locally advanced unresectable or metastatic triple-negative breast cancer (TNBC), according to findings from the phase 3 ASCENT-04/KEYNOTE-D19 trial (NCT05382286) published in The New England Journal of Medicine.

At a median follow-up of 14.0 months (range, 0.1-28.6), the median PFS as assessed by blinded independent central review (BICR) was 11.2 months (95% CI, 9.3-16.7) in the sacituzumab govitecan plus pembrolizumab arm (n = 221) compared with 7.8 months (95% CI, 7.3-9.3) in the chemotherapy plus pembrolizumab arm (n = 222; HR, 0.65; 95% CI, 0.51-0.84; P < .001). The 12-month PFS rate was 48% (95% CI, 41%-56%) in the investigational arm vs 33% (95% CI, 26%-40%) in the control arm. Overall survival (OS) data were immature at the time of the primary analysis.

This open-label, international trial enrolled adult patients with locally advanced unresectable or metastatic TNBC who had received no prior therapy for advanced disease and whose tumors were PD-L1–positive (defined as having a combined positive score [CPS] ≥ 10). Patients were randomly assigned 1:1 to receive sacituzumab govitecan at 10 mg/kg intravenously (IV) on days 1 and 8 plus pembrolizumab at 200 mg IV on day 1 of each 21-day cycle, or physician's choice of chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) plus pembrolizumab at 200 mg on day 1 of each 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or death. PFS by BICR served as the primary end point. Secondary end points included OS, objective response rate (ORR), duration of response (DOR), time to response (TTR), and safety.

Between October 17, 2022, and August 21, 2024, 443 patients were enrolled. The median age was 54 years (range, 23-88) in the sacituzumab govitecan arm vs 55 years (range, 27-82) in the chemotherapy arm. All patients were female and had PD-L1–positive disease, and most patients in the respective arms had an ECOG performance status of 0 (71% vs 69%). Disease status at random assignment in both arms included metastatic at initial diagnosis (34%), recurrent within 6 to 12 months after curative-intent treatment (18%), and recurrent more than 12 months after curative-intent treatment (48%).

The ORR was 60% (95% CI, 53-66) in the sacituzumab govitecan plus pembrolizumab group, including a complete response (CR) rate of 13% and a partial response (PR) rate of 47%. In the chemotherapy plus pembrolizumab group, the ORR was 53% (95% CI, 46-60; OR, 1.3; 95% CI, 0.9-1.9), with a CR rate of 8% and a PR rate of 45%. Among responders, the median DOR was significantly longer with sacituzumab govitecan plus pembrolizumab, at 16.5 months (95% CI, 12.7-19.5) compared with 9.2 months (95% CI, 7.6-11.3) in the chemotherapy arm. The median TTR was 1.9 months in both treatment groups. Subgroup analyses showed that the PFS benefit with the antibody-drug conjugate (ADC)–based combination was consistent across predefined patient subgroups, including age, geographic region, and disease status.

In separate research, investigators at the University of Missouri developed a very small antibody that seeks out EphA2, a protein frequently present in cancer tumors. They radioactively labeled the antibody to make it visible during positron emission tomography (PET) scans. In experiments using mice, this cancer detecting approach clearly illuminated tumors that produced EphA2. The results suggest that tagging the antibody could help doctors detect cancers that contain this protein and determine which patients might respond to therapies designed to target EphA2-positive tumor cells while leaving healthy tissue unharmed.

The new targeted approach is noninvasive, and results from the imaging can be obtained in hours rather than days. Doctors currently depend on biopsies and MRI scans to evaluate tumors in cancer patients. These methods can be invasive, require significant time, and often provide limited insight into the specific proteins found within cancer cells. The study, titled "Preclinical evaluation of anti-EphA2 minibody-based immunoPET agent as a diagnostic tool for cancer," was published in Molecular Imaging and Biology.

Data from a real-world multicenter analysis shared during the 2026 Transplantation and Cellular Therapy Meetings suggested that CD20-targeted bispecific antibodies (BsAbs) had activity after CD19-targeted CAR T-cell therapy in patients with mantle cell lymphoma, although longer follow-up is needed to understand the durability of response.

In the entire cohort (n = 20), the objective response rate achieved with BsAbs was 70%, which included a complete response (CR) rate of 45%. At a median follow-up of 8.9 months, the median duration of response (DOR) had not yet been reached (NR), the median progression-free survival (PFS) was 8.9 months, and the median overall survival was also NR.

When broken down further, those who received mosunetuzumab-axgb (Lunsumio)/polatuzumab vedotin-piiq (Polivy; n = 9) achieved an ORR of 76% with a CR rate of 56% with BsAbs. At a median follow-up of 8.9 months, the median DOR was 7.5 months, the median PFS was 8.9 months, and the median OS was NR. Those who received glofitamab-gxbm (Columvi; n = 11) experienced an ORR of 64%, which included a CR rate of 36% with BsAbs. At a median follow-up of 8.9 months, the median DOR, PFS, and OS were all NR. In those who received brexucabtagene autoleucel (Tecartus; brexu-cel; n = 10), the ORR was 60%, and the CR rate was 50%; at a median follow-up of 12.7 months, the median DOR was NR, the median PFS was 4.3 months, and the median OS was NR.

Additional data indicated that outcomes were inferior among patients who experienced early relapse after CAR T exposure (n = 10). In these patients, the median DOR was 7.5 months, the median PFS was 3.3 months, and the median OS was 7.6 months. In comparison, those with late relapse to CAR T (n = 10) experienced a median DOR (P = .57), PFS (P = .065), and OS (P = .13) that was NR.

The retrospective multicenter study assessed the use of BsAbs in those who were diagnosed with mantle cell lymphoma and who were receiving treatment at 10 medical centers throughout the United States. Of the 31 total patients with this disease who received treatment at the centers that comprised the Collaborative US Bispecific Consortium, 20 were administered BsAbs post CAR T-cell therapy and were included in the analysis. In the entire cohort of 20 patients, the median age was 64 years (range, 48-85), and most were male (80%). The median ECOG performance status of patients was 1 (range, 0-3). Moreover, patients were fairly heavily pretreated, having received a median of 5 prior lines of therapy (range, 2-9).