Research Rewind: Phase 3 Breast Cancer Data Highlights From Q1 2026

Breast cancer research hit the ground running at the start of 2026, with several clinical trial data sets making their way onto the scene. Need a refresher? We’ve got you covered with this recap of recent phase 3 data announcements and highlights, many of which are poised to influence clinical practice in the near future.

How did izalontamab brengitecan (iza-bren; BL-B01D1) perform in patients with triple-negative breast cancer (TNBC)?

In a prespecified interim analysis of the phase 3 BL-B01D1-307 trial (NCT06382142), treatment with iza-bren induced statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) vs physician’s choice of chemotherapy in patients with previously treated, unresectable, locally advanced or metastatic TNBC who had progressed after prior taxane therapy.¹ These PFS and OS findings met the study’s dual primary end points, according to a news release. Full trial findings are expected to be shared at an upcoming medical meeting.

Notably, iza-bren is a HER3- and EGFR-directed bispecific antibody-drug conjugate (ADC). The BL-B01D1-307 trial investigated the ADC in adult patients with unresectable, locally advanced or metastatic TNBC who had received 1 or 2 prior lines of chemotherapy in the locally advanced or metastatic settings, as well as a prior taxane.² Patients were also required to have an expected survival time of at least 3 months, an ECOG performance status of 0 or 1, and measurable disease per RECIST 1.1 criteria.

Patients in the iza-bren arm received the ADC intravenously for one 3-week cycle; patients who achieved clinical benefit from the agent could continue treatment for additional cycles until disease progression, intolerable toxicity, or other reasons. Patients in the chemotherapy arm received physician’s choice of eribulin, vinorelbine, gemcitabine, or capecitabine on the same schedule as the iza-bren arm.

What outcomes have been seen with giredestrant plus palbociclib (Ibrance) in estrogen receptor (ER)-positive, HER2-negative breast cancer?

An analysis of the phase 3 persevERA trial (NCT04546009) showed that patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer who received giredestrant plus palbociclib achieved a numerical PFS benefit compared with those who received letrozole plus palbociclib; however, this improvement was not statistically significant, and thus, the trial did not meet its primary end point.³ Of note, the safety profile of giredestrant plus palbociclib was deemed manageable and consistent with the known toxicities associated with each of the individual drugs, according to a news release. Full results of the trial are expected to be presented at a future medical meeting.

The persevERA trial enrolled adult patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer that was not amenable to curative-intent therapy.⁴ Patients could not have received prior systemic therapy for locally advanced or metastatic disease and needed to have measurable disease per RECIST 1.1 criteria, adequate organ function, and an ECOG performance status of 0 or 1.

Patients were randomly assigned 1:1 to receive:

• giredestrant once daily, palbociclib at 125 mg on days 1 to 21 of each 28-day cycle, and a letrozole-matched placebo once daily; or
• a giredestrant-matched placebo once daily, letrozole once daily, and palbociclib at the same dose and schedule as the investigational arm.

What is the efficacy of palbociclib in hormone receptor–positive, HER2-positive advanced breast cancer?

An analysis of the phase 3 PATINA trial (NCT02947685), published in January 2026 in the New England Journal of Medicine and previously presented at the 2025 San Antonio Breast Cancer Symposium, showed that the addition of palbociclib to standard maintenance HER2-targeted or endocrine therapy significantly improved PFS vs standard therapy alone in patients with hormone receptor–positive, HER2-positive metastatic breast cancer whose disease had not progressed following 4 to 8 cycles of chemotherapy in combination with HER2-targeted therapy.⁵

At a median follow-up of 53.5 months, the median PFS in the palbociclib group (n = 261) was 44.3 months (95% CI, 32.4-56.8) vs 29.1 months (95% CI, 23.3-38.6) in the standard-of-care (SOC) group (n = 257; HR, 0.75; 95% CI, 0.59-0.96; 2-sided P = .02). The confirmed overall response rate (cORR) was 32.9% (95% CI, 26.9%-39.4%) in the palbociclib arm vs 24.8% (95% CI, 19.3%-30.0%) in the control arm. At the data cutoff, 60 and 63 patients in these respective arms had died (HR, 0.86; 95% CI, 0.61-1.23). Per the trial protocol, the final OS analysis will be conducted after 247 deaths have occurred.

Patients were randomly assigned 1:1 to receive maintenance therapy with HER2-targeted and endocrine therapies with or without palbociclib. Endocrine therapies included fulvestrant (Faslodex) or an aromatase inhibitor, and premenopausal patients were also required to receive ovarian suppression. Palbociclib was given at 125 mg daily for the first 21 days of each 28-day cycle.

Investigator-assessed PFS served as the primary end point. Secondary end points included cORR, OS, and safety.

Trial investigators noted that the addition of palbociclib was associated with increased toxic effects. Common grade 3 or higher adverse effects (AEs) seen in the palbociclib vs control groups, respectively, were neutropenia (60.5%; 2.0%) and leukopenia (16.1%; 0.8%).

How has first-line sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) performed in metastatic TNBC?

Data from the phase 3 ASCENT-04/KEYNOTE-D19 trial (NCT05382286), published in January 2026 in the New England Journal of Medicine and previously presented at the 2025 American Society of Clinical Oncology Annual Meeting, demonstrated that sacituzumab govitecan in combination with pembrolizumab generated a significant PFS benefit vs chemotherapy plus pembrolizumab in the first-line setting in patients with PD-L1–positive, locally advanced unresectable or metastatic TNBC. At a median follow-up of 14.0 months (range, 0.1-28.6), the median PFS per blinded independent central review in the sacituzumab govitecan arm (n = 221) was 11.2 months (95% CI, 9.3-16.7) vs 7.8 months (95% CI, 7.3-9.3) in the chemotherapy arm (n = 222; HR, 0.65; 95% CI, 0.51-0.84; P < .001). The OS data were not mature at the time of the primary analysis.

This trial enrolled adult patients with locally advanced unresectable or metastatic TNBC who had not been previously treated for advanced disease and who had PD-L1–positive disease. Patients were randomly assigned 1:1 to receive:

• sacituzumab govitecan at 10 mg/kg on days 1 and 8 in combination with pembrolizumab at 200 mg on day 1 of each 21-day cycle; or
• physician’s choice of paclitaxel, nab-paclitaxel (Abraxane), or gemcitabine plus carboplatin in combination with pembrolizumab at the same dose and schedule as in the investigational arm.

The investigators noted that the safety profile of sacituzumab govitecan plus pembrolizumab was consistent with those of the individual drugs. The most common grade 3 or higher AEs in the sacituzumab govitecan and chemotherapy arms, respectively, were neutropenia (43%; 45%), diarrhea (10%; 2%), febrile neutropenia (8%; 2%), and fatigue (8%; 3%).

Further viewing: Following an updated safety readout from this trial, Sara M. Tolaney, MD, MPH, of Dana-Farber Cancer Institute in Boston, Massachusetts, sat down with OncLive to share her thoughts,⁶ noting that, “numerically, there were fewer immune-related AEs with sacituzumab govitecan plus pembrolizumab compared with chemotherapy plus pembrolizumab, [which] was reassuring.”

How has anbenitamab plus docetaxel performed in HER2-positive breast cancer?

An analysis of the phase 3 Neo-Healer trial (KN026-004; NCT06747338) showed that neoadjuvant anbenitamab injection (KN026) plus albumin-bound docetaxel (HB1801) significantly improved total pathologic complete response (tpCR) outcomes vs SOC therapy in patients with HER2-positive early or locally advanced breast cancer.⁷ These tpCR findings met the primary end point of the trial. A full presentation of these data is anticipated at a future medical meeting.

The ongoing Neo-Healer trial is enrolling adult patients with histologically and cytologically confirmed early or locally advanced HER2-positive breast cancer, an ECOG performance status of 0 or 1, and adequate bone marrow and organ function.⁸ Patients are randomly assigned 1:1 to receive:

• anbenitamab in combination with albumin-bound docetaxel with or without carboplatin; or
• trastuzumab (Herceptin) in combination with pertuzumab (Perjeta) and docetaxel with or without carboplatin.

References

1. SystImmune and Bristol Myers Squibb highlight positive phase III interim topline results for izalontamab brengitecan (iza-bren) in previously treated unresectable locally advanced or metastatic triple-negative breast cancer. News release. SystImmune. February 26, 2026. Accessed March 31, 2026. https://tinyurl.com/5n6yrdhn
2. A study comparing BL-B01D1 with chemotherapy of physician’s choice in patients with unresectable locally advanced or metastatic triple-negative breast cancer. ClinicalTrials.gov. Updated November 17, 2025. Accessed March 31, 2026. https://clinicaltrials.gov/study/NCT06382142
3. Genentech provides update on phase III persevErA study in ER-positive advanced breast cancer. News release. Genentech. March 8, 2026. Accessed March 31, 2026. https://www.gene.com/media/press-releases/15106/2026-03-08/genentech-provides-update-on-phase-iii-p
4. A study evaluating the efficacy and safety of giredestrant combined with palbociclib compared with letrozole combined with palbociclib in participants with estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancer (persevERA Breast Cancer). ClinicalTrials.gov. Updated February 20, 2026. Accessed March 9, 2026. https://clinicaltrials.gov/study/NCT04546009
5. Metzger O, Mandrekar S, Goel S, et al. Palbociclib for hormone-receptor-positive, HER2-positive advanced breast cancer. N Engl J Med. 2026;394(5):451-462. doi:10.1056/NEJMoa2511218
6. Tolaney SM. Dr Tolaney on updated safety findings with sacituzumab govitecan plus pembrolizumab in PD-L1–positive TNBC. OncLive. December 23, 2025. Accessed March 31, 2026. https://www.onclive.com/view/dr-tolaney-on-updated-safety-findings-with-sacituzumab-govitecan-plus-pembrolizumab-in-pd-l1-positive-tnbc
7. Phase III clinical study of anbenitamab (KN026) in combination with docetaxel (albumin-bound) (HB1801) for neoadjuvant treatment of HER2+ breast cancer meets primary endpoint. News release. CSPC Pharmaceutical Group. March 31, 2026. Accessed March 31, 2026. https://doc.irasia.com/listco/hk/cspc/announcement/a260331.pdf
8. A phase III study of KN026 in combination with HB1801 ± carboplatin as neoadjuvant treatment for early or locally advanced HER2-positive breast cancer (Neo-Healer). ClinicalTrials.gov. Updated April 24, 2025. Accessed March 31, 2026. https://clinicaltrials.gov/study/NCT06747338