BriaCell Bets an Off-the-Shelf Cell Vaccine Can Extend Life After ADCs in Metastatic Breast Cancer

For patients with metastatic breast cancer, antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (Enhertu; AstraZeneca/Daiichi Sankyo) and sacituzumab govitecan (Trodelvy; Gilead) now occupy space that once belonged to sequential chemotherapy, and they have extended survival in randomized trials.¹⁻⁴ But toxicities accumulate. In ASCENT (NCT02574455), 51% of patients receiving sacituzumab govitecan had grade 3 or higher neutropenia,¹ and in DESTINY-Breast04 (NCT03734029), 12.1% receiving trastuzumab deruxtecan developed interstitial lung disease or pneumonitis.⁴

Once ADCs fail, patients face bleak prospects: in the final ASCENT analysis, patients with triple-negative breast cancer (TNBC) given physician’s choice chemotherapy had median overall survival (OS) of 6.9 months.²

BriaCell Therapeutics seeks to address that gap with Bria-IMT, an off-the-shelf, whole-cell immunotherapy now in a pivotal phase 3 trial. The company presented final phase 2 data at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and just presented biomarker findings this weekend at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain.⁵⁻⁷

“We’re still projecting that we’ll get that first interim look this year,” BriaCell President and CEO William V. Williams, MD, FACP, said in an October 8, 2026, interview with The American Journal of Managed Care® (AJMC®).

Why a Vaccine for Breast Cancer?

Bria-IMT began in the lab of Charles L. Wiseman, MD, at St. Vincent Medical Center in Los Angeles, who vaccinated more than 250 patients with irradiated cancer cell lines, Williams said, before engineering a breast cancer line to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). The resulting line, SV-BR-1-GM, expresses human leukocyte antigen (HLA) class II molecules and can directly activate CD4+ helper T cells.⁸ In the phase 1/2a trial, every patient whose tumors regressed was HLA-matched to the cell line.⁹

Earlier GM-CSF–secreting whole-cell vaccines did not survive phase 3; Cell Genesys halted both phase 3 trials of GVAX in prostate cancer in 2008, one after an imbalance in deaths and the other for futility.¹⁰ Williams cited 2 differences. The first is the cell line.

“It expresses class II HLA molecules, which elicit T-cell help, and we showed [in a published paper] that these are functional molecules, that we can actually activate CD4-positive helper T cells with the endogenous class II HLA molecules on the Bria-IMT cells,” he said. “And that’s important because it provides boosting for the immune response.”

The second is the regimen: low-dose cyclophosphamide to reduce immune suppression, intradermal inoculations of the cells, then microdoses of interferon alfa injected into the same sites.

“Dr Wiseman very wisely [did not] just rely on GM-CSF as a booster. He also used this microdose alpha-interferon to steer the immune response in the right direction,” Williams said. “We think that actually makes a big difference in terms of getting not just an immune response, but the right kind of immune response.”

Bria-ABC: Designed for Full Approval

Bria-ABC (NCT06072612) randomly assigns patients who have exhausted approved therapies to Bria-IMT plus the PD-1 inhibitor retifanlimab (Zynyz; Incyte), Bria-IMT alone, or physician’s choice chemotherapy, with OS as the primary end point.¹¹^,¹² Designed for 404 patients,¹² it had enrolled more than 230 by May,¹³ and now has more than 80 sites in 15 states.¹⁴ The regimen has received FDA Fast Track designation, and Bria-ABC was listed as a “trial to watch” for 2026 by Nature Medicine.^14,15

“If we see a 40% reduction [in mortality], we can declare victory at our first interim look, [at] 144 mortalities. But if that doesn’t pan out, then we can continue the study and see if we see a 30% reduction,” Williams said in the interview. “In either case, FDA has agreed that that could support full approval because we’re looking at mortality. So, not accelerated approval, but full approval.”

Earlier this year, BriaCell widened its topline guidance from the first half of 2026 to 2026 overall.¹³ “This is typical in phase 3 studies,” Williams said. “It’s a small delay, but we’re relatively on track.”

Final Phase 2 Data: A Long-Term Survivor Cohort

The final phase 2 analysis (NCT03328026) included 32 patients who had received a median of 6 prior therapies.⁵^,⁶^,¹⁶ With the regimen chosen for phase 3, median OS was 16.6 months, with more than 55% of patients alive at 1 year and more than 27% at 2 years.⁶ Starting the checkpoint inhibitor in cycle 1 rather than cycle 2 was associated with median OS of 13.3 months vs 7.4 months. There were no treatment-related discontinuations, and injection site reactions were mostly mild.⁶ Patients with a positive delayed-type hypersensitivity response had median OS of 11.9 vs 4.7 months without one.⁵

“The phase 2 study of the combination of a whole-cell vaccine with anti–PD-1 demonstrated a tolerable safety profile and the emergence of a long-term survivor cohort inclusive of the heavily pretreated nature of these patients,” Saranya Chumsri, MD, principal investigator of Bria-ABC and professor of oncology at Mayo Clinic Florida, said instatement following the presentation of the data at ASCO.⁵

At ESMO, a pooled analysis presented Friday involved 111 patients treated with checkpoint inhibitors, some also receiving Bria-IMT. Results found that PD-L1 expression on circulating cancer-associated macrophage-like cells at approximately 3 months was associated with OS (HR, 2.27; P = .042); tumor PD-L1 combined positive score was not.⁷ The company said further validation is needed.⁷

Where Bria-IMT Fits: After the ADCs

Bria-ABC enrolls patients at the end of today’s sequence: after endocrine therapy, CDK4/6 inhibitors, and ADCs in hormone receptor–positive (HR+) disease, and after chemoimmunotherapy and sacituzumab in TNBC. At baseline, 84% had received an ADC, 61% a CDK4/6 inhibitor, and 27% a checkpoint inhibitor.⁶

“The way our phase 3 is going, it’s post-ADC in over 80% of the patients,” Williams said. “In our phase 2, we had 23 patients who were ADC experienced—been on an ADC and had progressed in spite of it—and they actually did very well.”

He compared the phase 2 results with sacituzumab, which produced median OS of 14.4 months in HR+/HER2-negative disease in TROPiCS-02 (NCT03901339)³ and 11.8 months in TNBC in ASCENT.² “We’re at over 16 months,” he said. Those are cross-trial comparisons, and the 16.6-month figure comes from 21 patients in a nonrandomized study⁶; Bria-ABC will provide the controlled test. If it succeeds, Bria-IMT would take the place of single-agent chemotherapy rather than add another cytotoxic payload.

Williams has also argued that off-the-shelf platforms suit late-stage disease better than personalized mRNA vaccines. “For patients with rapidly progressing, heavily pretreated solid tumors, waiting weeks for custom manufacturing is often not a viable option,” he wrote in a September essay.¹⁷

Next Generation: Matching 99% of Patients

Because HLA matching tracked response,⁹ BriaCell engineered cell lines to express additional HLA alleles. The first-generation Bria-OTS (NCT06471673) was tolerable at doses up to 60 million cells; 1 patient received 17 cycles with 12 months of disease control.⁵^,¹⁸ In May, the FDA cleared an investigational new drug application for Bria-BRES+, which adds costimulatory molecules and cytokines, ahead of a phase 1/2a study in metastatic breast cancer.¹⁹ Versions for prostate cancer and melanoma follow.

“We figure, based on our analysis, that we can get 99% of the patients to have at least a single match, and 90% to have a double match in class I and class II HLA,” Williams said. The added molecules are meant “to make this more like an actual activated dendritic cell, which are the cells that start immune responses.”

The Managed Care Factor

Blinded quality-of-life data from Bria-ABC, including time without symptoms or toxicity (TWiST), showed global health status and key functional domains were largely preserved.⁵ “These data from the ongoing pivotal phase 3 Bria-ABC study highlight Bria-IMT’s potential to preserve quality of life, limit toxicity, and potentially support self-administration—benefits that would be clinically meaningful for patients,” Adam M. Brufsky, MD, PhD, FACP, of the University of Pittsburgh School of Medicine and Magee-Womens Cancer Program, said in the company’s statement highlighting its ASCO presentations.⁵

In the interview, Williams added, “The main adverse effect that we’re seeing is local irritation at the inoculation sites, which is expected because you’re getting an immune response, and so there’s some local itchiness and redness and swelling, and it goes away in a few days.”

Cyclophosphamide is given in an infusion center; 2 to 3 days later, patients receive 4 intradermal inoculations, followed 2 days after that by interferon alfa, in 3-week cycles. “It’s really not a very difficult procedure, and it can be done in a physician’s office. And we think it could even be done by a visiting nurse,” he said.

In response to questions from AJMC®, Williams said BriaCell has held early discussions with selected payers about where the therapy fits—both in treatment sequence and in pricing. “I think it’s probably comparable to a lot of the ADCs. Clearly, a lot less than a CAR T treatment,” Williams said. “We’re not going to come in too high so that people would balk using us, and then of course we can’t come in too low, or we can’t sustain the operation.”

For patients who have exhausted other options, he said, tolerability is the point. “We’ve had patients on the therapy for 2 years. It’s very well tolerated, and patients don’t generally drop out because of issues with the therapy.”

References

1. Bardia A, Hurvitz SA, Tolaney SM, et al; ASCENT Clinical Trial Investigators. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529-1541. doi:10.1056/NEJMoa2028485
2. Bardia A, Rugo HS, Tolaney SM, et al. Final results from the randomized phase III ASCENT clinical trial in metastatic triple-negative breast cancer and association of outcomes by human epidermal growth factor receptor 2 and trophoblast cell surface antigen 2 expression. J Clin Oncol. 2024;42(15):1738-1744. doi:10.1200/JCO.23.01409
3. Rugo HS, Bardia A, Marmé F, et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2023;402(10411):1423-1433. doi:10.1016/S0140-6736(23)01245-X
4. Modi S, Jacot W, Yamashita T, et al; DESTINY-Breast04 Trial Investigators. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
5. BriaCell presentations highlight positive clinical data for bria-IMT at ASCO 2026. News release. BriaCell Therapeutics Corp. May 22, 2026. Accessed October 25, 2026. https://www.globenewswire.com/news-release/2026/05/22/3300068/0/en/briacell-presentations-highlight-positive-clinical-data-for-bria-imt-at-asco-2026.html
6. BriaCell presents positive clinical data at ASCO 2026. News release. BriaCell Therapeutics Corp. June 1, 2026. Accessed October 25, 2026. https://www.biospace.com/press-releases/briacell-presents-positive-clinical-data-at-asco-2026
7. BriaCell announces ESMO 2026 poster highlighting circulating immune biomarker associated with clinical outcomes in metastatic breast cancer. News release. BriaCell Therapeutics Corp. October 23, 2026. Accessed October 25, 2026. https://www.biospace.com/press-releases/briacell-announces-esmo-2026-poster-highlighting-circulating-immune-biomarker-associated-with-clinical-outcomes-in-metastatic-breast-cancer
8. Lacher MD, Bauer G, Fury B, et al. SV-BR-1-GM, a clinically effective GM-CSF-secreting breast cancer cell line, expresses an immune signature and directly activates CD4+ t lymphocytes. Front Immunol. 2018;9:776. doi:10.3389/fimmu.2018.00776
9. Wiseman CL, Holmes JP, Calfa C, et al. Results of a phase I/IIa trial of SV-BR-1-GM inoculation with low-dose cyclophosphamide and interferon alpha (Bria-IMT) in metastatic breast cancer. Hum Vaccin Immunother. 2024;20(1):2379864. doi:10.1080/21645515.2024.2379864
10. Cell Genesys announces termination of VITAL-1 phase 3 trial of GVAX immunotherapy for prostate cancer. Fierce Biotech. October 16, 2008. Accessed October 25, 2026. https://www.fiercebiotech.com/biotech/cell-genesys-announces-termination-of-vital-1-phase-3-trial-of-gvax-immunotherapy-for
11. Study of the bria-IMT regimen and CPI vs physicians’ choice in advanced metastatic breast cancer (BRIA-ABC). ClinicalTrials.gov. Accessed October 25, 2026. https://clinicaltrials.gov/study/NCT06072612
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13. BriaCell phase 3 Bria-IMT study enrollment surpasses 230 patients. News release. BriaCell Therapeutics Corp. May 12, 2026. Accessed October 25, 2026. https://finviz.com/news/353301/briacell-phase-3-bria-imt-study-enrollment-surpasses-230-patients
14. BriaCell’s pivotal phase 3 metastatic breast cancer study expands to leading cancer center. News release. BriaCell Therapeutics Corp. September 8, 2026. Accessed October 25, 2026. https://finviz.com/news/389433/briacells-pivotal-phase-3-metastatic-breast-cancer-study-expands-to-leading-cancer-center
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16. Combination study of SV-BR-1-GM in combination with INCMGA00012 and epacadostat. ClinicalTrials.gov. Accessed October 25, 2026. https://clinicaltrials.gov/study/NCT03328026
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