Research Rewind: Notable Phase 1/2 Breast Cancer Trial Readouts From Quarter 1 of 2026

A variety of novel breast cancer agents erupted onto the scene to open 2026. Interested in how early-phase studies may shake out to influence further research and help shape the future of breast oncology? Read our recap of the most recent phase 1/2 data highlights.

How has paxalisib (formerly GDC-0084)-based therapy performed in late-stage metastatic triple-negative breast cancer (TNBC)?

In an ongoing phase 1b study (ACTRN12624001340527), the combination of paxalisib, pembrolizumab (Keytruda), and chemotherapy induced responses in patients with stage IV metastatic TNBC.¹ Among 3 patients treated with this regimen, 2 achieved partial responses. The third patient achieved a confirmed metabolic complete response (CR) following re-treatment with the regimen under an expanded-access protocol. Notably, responders had visceral disease and metastases in multiple organs. The median time on treatment was approximately 6.1 months.

Furthermore, the safety profile of paxalisib at 30 mg daily in combination with pembrolizumab and chemotherapy has been deemed generally favorable. Approximately 75% of the adverse effects (AEs) reported in the trial were determined to be unrelated or not likely to be related to paxalisib. The AEs deemed related to paxalisib were mild-to-moderate. When studied at the 30-mg daily dose, investigators observed 1 case of grade 1 hyperglycemia, which did not require intervention. Additionally, 2 serious AEs were reported, neither of which were deemed related to paxalisib.

This multicenter, open-label, randomized trial was initiated in June 2025 and is evaluating the safety, tolerability, and preliminary activity of paxalisib in patients with advanced breast cancer, including TNBC. Paxalisib in being studied in combination with pembrolizumab and chemotherapy, or with olaparib (Lynparza) for patients with BRCA mutations.

This phase 1b trial is expected to reach its target enrollment of 12 patients with TNBC by the end of 2026, with a topline data readout anticipated in the beginning of 2027.

What predictive biomarker data might influence the use of evorpacept (ALX148) plus zanidatamab-hrii (Ziihera) in HER2-positive breast cancer?

Data from an exploratory analysis of a phase 1/2 trial (NCT05027139) showed that CD47 expression levels predicted response to treatment with the CD47 inhibitor evorpacept in combination with zanidatamab in heavily pretreated patients with confirmed HER2-positive metastatic breast cancer.²

Full data from this portion of the trial have been submitted for presentation at an upcoming scientific congress.

This trial is investigating evorpacept plus zanidatamab in pretreated patients with unresectable, locally advanced or metastatic HER2-expressing breast and other cancers.^2,3 Cohort 1 enrolled patients with HER2-positive breast cancer who had received a minimum of 3 prior regimens.

In the safety portion of part 1, patients in cohort 1 were treated with zanidatamab at 1200 mg (if weighing <70 kg) or 1600 mg (if weighing ≥70 kg) in combination with evorpacept at 20 mg/kg (part 1A dose) or 30 mg/kg (part 1B dose) every 2 weeks in 28-day cycles.³ In the part 2 expansion portion, patients in cohort 1 received the combination at the recommended phase 2 dose, which included the part 1B dose of evorpacept.

In part 1, safety served as the primary end point. In part 1, the primary end point was confirmed overall response rate (cORR).

Previously, primary findings from this study were presented at the 2024 San Antonio Breast Cancer Symposium and showed that of patients in cohort 1 who had centrally confirmed HER2-positive breast cancer, the combination yielded a cORR of 55.6% (95% CI, 21.2%-86.3%); all responses were partial. Furthermore, the median PFS was 7.4 months (95% CI, 0.6-not evaluable [NE]), the disease control rate was 77.8% (95% CI, 40.0%-97.2%), and the median duration of response (DOR) was NE (range, 5.6 months-25.9 months). Notably, an exploratory analysis showed that responses to this regimen were mostly seen in patients with high CD47 expression levels.²

What is the efficacy of Bria-IMT (SV-BR-1-GM) in metastatic breast cancer?

Data from a phase 2 trial showed that in patients with metastatic breast cancer, treatment with the phase 3 formulation of Bria-IMT plus a checkpoint inhibitor and chemotherapy (n = 37) generated a median overall survival (OS) of 15.6% and a 2-year OS rate of 32%. No treatment discontinuations related to Bria-IMT have been reported.⁴

This trial enrolled 54 patients with heavily pretreated metastatic breast cancer who had received a median of 6 prior therapies. Patients treated with the same formulation of the Bria-IMT regimen that is being investigated in the pivotal phase 3 BRIA-ABC trial (NCT06072612) received cyclophosphamide at 300 mg/m² on day –2 or –3, followed by Bria-IMT on day 0 divided into 4 inoculations, in combination with a checkpoint inhibitor plus interferon on days 1 through 3.⁵ 

What is the efficacy of neoadjuvant INT230-6 in patients with TNBC?

Preliminary data from the phase 2 INVINCIBLE-4 trial (NCT06358573) demonstrated a pathologic complete response (pCR) rate of 71.4% among patients with TNBC who received INT230-6 prior to standard of care (SOC; n = 7) vs 33% among patients who received SOC alone (n = 6).⁶ Regarding safety, investigators observed 44% fewer grade 3 or higher AEs among patients in the INT230-6 arm vs those in the SOC-alone arm. In the investigational arm, 14 grade 3 or higher AEs have been reported, 1 of which was deemed a common immune-related AE associated with checkpoint immunotherapy. In the SOC-alone arm, 25 grade 3 or higher SOC-related AEs have been reported, 4 of which were deemed common or rare AEs associated with immune checkpoint inhibitors.

SOC in this trial consists of the phase 3 KEYNOTE-522 trial (NCT03036488) regimen of neoadjuvant pembrolizumab, followed by paclitaxel, then followed by carboplatin and doxorubicin or epirubicin with cyclophosphamide.

INVINCIBLE-4 has an expected total enrollment of 61 patients. The pCR analysis is ongoing.

How has atirmociclib (PF-07220060) performed in metastatic breast cancer?

Data from the phase 2 FOURLIGHT-1 trial (NCT06105632) showed that among patients with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer who had previously received CDK4/6 inhibitor–based therapy, treatment with the next-generation CDK4 inhibitor atirmociclib in combination with fulvestrant (Faslodex) in the second-line setting led to a statistically significant and clinically meaningful PFS improvement vs treatment with fulvestrant or everolimus in combination with exemestane (HR, 0.60; 95% CI, 0.440-0.825; P = .0007), meeting the trial’s primary end point.⁷ Notably, this PFS benefit was consistent across all prespecified patient subgroups. OS data were immature at the time of the analysis. The safety profile of atirmociclib was also deemed manageable, tolerable, and consistent with data from prior studies. In total, 6.4% of patients discontinued atirmociclib due to treatment-emergent AEs.

Detailed data from FOURLIGHT-1 are planned to be submitted for sharing at an upcoming medical conference.

This open-label, randomized, multicenter trial enrolled 264 patients across 14 countries. Patients needed to have disease that had progressed following treatment with a CDK4/6 inhibitor. Investigator-assessed PFS served as the primary end point. Secondary end points included OS, ORR, DOR, and clinical benefit.

References

1. Kazia Therapeutics reports encouraging preliminary clinical responses in ongoing phase 1b study of paxalisib in late-stage metastatic triple-negative breast cancer. News release. Kazia Therapeutics. January 27, 2026. Accessed April 2, 2026. https://www.kaziatherapeutics.com/site/pdf/9632aa12-66ab-4b4b-814d-bf37679d72b6/Kazia-Therapeutics-Reports-Encouraging-Preliminary-Clinical-Responses-in-Ongoing-Phase-1b-Study-of-Paxalisib-in-LateStage-Metastatic-TripleNegative-Breast-Cancer.pdf?Platform=ListPage
2. New data demonstrate CD47 expression level helps predict response to ALX Oncology’s evorpacept in combination with Ziihera (zanidatamab-hrii) in advanced HER2-positive breast cancer. News release. ALX Oncology Holdings Inc. January 30, 2026. Accessed April 2, 2026. https://ir.alxoncology.com/news-releases/news-release-details/new-data-demonstrate-cd47-expression-level-helps-predict/
3. Montero AJ, Wisinski KB, Fang B, et al. Zanidatamab in combination with evorpacept in HER2-positive and HER2-low metastatic breast cancer: results from a phase 1b/2 study. Presented at: 2024 San Antonio Breast Cancer Symposium. December 10-13, 2024. San Antonio, Texas. PS8-09
4. BriaCell highlights extended >18-47 months survival in phase 2 metastatic breast cancer patients. News release. BriaCell Therapeutics Corp. January 27, 2026. Accessed April 2, 2026. https://briacell.com/briacell-highlights-extended-18-47-months-survival-in-phase-2-metastatic-breast-cancer-patients/
5. Study of the Bria-IMT regimen and CPI vs physicians' choice in advanced metastatic breast cancer. (BRIA-ABC). ClinicalTrials.gov. Updated April 2, 2026. Accessed April 2, 2026. https://clinicaltrials.gov/study/NCT06072612
6. Intensity Therapeutics, Inc. Provides update on the phase 2 presurgical triple-negative breast cancer INVINCIBLE-4 study. News release. Intensity Therapeutics, Inc. March 12, 2026. Accessed April 2, 2026. https://ir.intensitytherapeutics.com/news-events/press-releases/detail/121/intensity-therapeutics-inc-provides-update-on-the-phase-2
7. Pfizer announces positive topline phase 2 results for next-generation CDK4 inhibitor, atirmociclib, in second-line metastatic breast cancer. News release. Pfizer Inc. March 17, 2026. Accessed April 2, 2026. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-topline-phase-2-results-next