ASCO GU 2026: A Phase II Clinical Trial of Neoadjuvant Sasanlimab and Stereotactic Body Radiation Therapy as an in Situ Vaccine for Cisplatin-Ineligible MIBC: The RAD VACCINE MIBC Clinical Trial

(UroToday.com) The 2026 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA, between February 26^th and 28^th, 2026, was host to the Poster Session B: Prostate Cancer and Urothelial Carcinoma. Dr. Raj Satkunasivam presented the poster: ECOG ACRIN EA8291 Cohort C: A phase II clinical trial of neoadjuvant sasanlimab and stereotactic body radiation therapy as an in situ vaccine for cisplatin-ineligible muscle invasive bladder cancer (MIBC): The RAD VACCINE MIBC clinical trial.

Dr. Satkunasivam began by highlighting that up to half of patients with MIBC are not candidates for cisplatin-based neoadjuvant chemotherapy, representing a significant unmet need. Immune checkpoint inhibitors have emerged as an alternative strategy, and combining them with local therapies such as SBRT may enhance antitumor immunity.^1-3 SBRT delivered at 8 Gy × 3 fractions can induce immunogenic cell death and potentially function as an in situ vaccine, augmenting systemic immune responses when paired with ICI.⁴

This prospective phase II trial enrolled patients with cT2–4aN0M0 MIBC who were cisplatin-ineligible or declined chemotherapy. Patients received sasanlimab (two 300 mg subcutaneous doses, 28 days apart) with SBRT to the bladder tumor (8 Gy × 3 fractions at 48-hour intervals, starting during the second ICI cycle) prior to radical cystectomy.

The study used a Simon two-stage design, enrolling 33 patients with pathologic complete response (pT0) as the primary endpoint. Secondary endpoints included safety, health-related quality of life, and recurrence-free survival, with exploratory correlative immune analyses. The study schema is shown below.

Between March 2022 and April 2025, 33 patients were enrolled; 73% had ≥cT3 disease. Four patients withdrew due to progression before cystectomy, and a total of 29 patients completed the intervention. Baseline characteristics are illustrated in the table below.

The trial met its primary endpoint:

• Pathologic complete response (pT0) rate was 44.8%.
• 75.9% of patients were downstaged to pT0/Ta/T1 at cystectomy.

With a median follow-up sufficient for early outcomes, the two-year metastasis-free survival was:

• 72.2% overall,
• 92.3% in patients achieving pCR,
• 56.3% in patients without pCR (p = 0.02).

Treatment was generally well tolerated. Grade ≥3 treatment-related adverse events occurred in 9.1% of patients, including hypothyroidism (21%), adrenal insufficiency (6.9%), and nephritis (3.5%), both managed with steroids. Grade ≥3 Clavien-Dindo 30-day surgical complications occurred in 13.8%, with no perioperative mortality. Importantly, there was no significant deterioration in EORTC QLQ-C30 quality-of-life scores during ICI therapy, SBRT, or after cystectomy.

Correlative analyses integrating tumor and peripheral immune profiling demonstrated distinct immune signatures associated with pathologic downstaging. UMAP-based clustering of CD45⁺ immune nuclei identified major immune lineages, supported by canonical marker gene expression. At baseline, patients who ultimately achieved downstaging (pT0/pTa/pT1/pCIS) showed enrichment of CD8⁺ T cells, whereas non-downstaged (≥pT2) patients exhibited increased regulatory T-cell abundance. Treatment was associated with expansion of these immune subsets in peripheral blood mononuclear cells, suggesting that both baseline immune contexture and therapy-induced immune modulation may contribute to pathologic response.

Moreover, high-resolution clustering of intratumoral CD8⁺ T cells identified multiple functionally distinct subpopulations, including naïve/stem-like, progenitor-exhausted, terminally exhausted, tissue-resident memory, ISG-high, and KLRG1⁺ effector subsets. At baseline, downstaged patients demonstrated enrichment of exhausted, progenitor-exhausted, tissue-resident memory, and interferon-primed CD8⁺ T-cell populations, consistent with a pre-existing, antigen-experienced immune microenvironment. Following treatment, there was a relative expansion of effector CD8⁺ T cells, supporting a model in which therapy reshapes the intratumoral immune landscape toward a more cytotoxic, antitumor phenotype associated with pathologic response. 

Furthermore, pseudotime trajectory analysis of intratumoral CD8⁺ T cells revealed four distinct differentiation pathways spanning naïve/stem-like to terminally exhausted states. Gene expression trends across pseudotime demonstrated coordinated upregulation of checkpoint (HAVCR2, LAG3, PDCD1), cytotoxic (GNLY, GZMB, IFNG), and exhaustion-associated (CXCL13, ENTPD1, TOX) markers, alongside dynamic changes in memory and effector-related genes. Importantly, pathological downstaging correlated with limited progression toward late terminally exhausted phenotypes, with preservation of earlier, progenitor-like and intermediate states. These findings suggest that maintaining a less terminally differentiated CD8⁺ T-cell landscape may be associated with improved pathologic response.
Another subset exhibited robust dendritic cell expansion associated with activated CD4+ T-cell responses, suggesting multiple immune pathways contributing to the response.

Dr. Satkunasivam concluded:

• The combination of SBRT and sasanlimab achieved a clinically meaningful pCR rate in cisplatin-ineligible MIBC.
• Downstaging rates were high, and pCR was strongly associated with improved metastasis-free survival.
• Toxicity was acceptable, with manageable immune-related events and no significant impact on quality of life.
• Correlative analyses suggest biologically distinct response mechanisms that may inform future patient selection.
• These findings support further investigation of in situ vaccination strategies, potentially in combination with additional systemic agents, to improve pCR and long-term disease control, with implications for organ preservation approaches.

Presented by: Raj Satkunasivam, MD, MS, FRCSC, Assistant Professor, Weill Cornell Medical College, Department of Urology, Houston Methodist Hospital

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