Durvalumab Plus BCG Demonstrates Manageable Safety Profile in BCG-Naive High-Risk NMIBC

The addition of durvalumab (Imfinzi) to BCG induction and maintenance therapy was associated with a manageable safety profile that was consistent with the known toxicities of the individual agents in patients with BCG-naive, high-risk non-muscle-invasive bladder cancer (NMIBC), according to data from the primary analysis of the phase 3b PATAPSCO study (NCT05943106) presented during the 2026 American Urological Association (AUA) Annual Meeting.¹

Among patients treated with durvalumab plus BCG (n = 99), 12.1% (95% CI, 6.4–20.2) experienced grade 3 or 4 adverse effects possibly related to any study treatment (PRAEs) within 6 months of treatment initiation, meeting the primary end point of the study. Each of the following grade 3/4 PRAEs was reported in 1% of patients: acute respiratory failure, increased amylase levels, arthralgia, autoimmune hepatitis, autoimmune nephritis, colitis, diabetic ketoacidosis, diarrhea, dyspnea, fatigue, hyperkalemia, hypertension, hypertransaminasemia, inflammation, increased lipase levels, peripheral swelling, pollakiuria, pulmonary embolism, and urinary tract infection.

“There are no new safety signals identified [with durvalumab plus BCG] and [the majority of] immune-mediated AEs [imAEs] were largely low grade. I think this supports the safety of the combination of this population.” -presenting author Mark D. Tyson, MD, MPH.

Tyson is a urologic oncologist in the Department of Urology, as well as as vice chair of research for the Department of Urology, vice chair of the Surgical and Procedural Committee, and chair of the Surgical Quality Subcommittee at Mayo Clinic in Phoenix, Arizona.

How was PATAPSCO designed?

PATAPSCO is an open-label, single-arm, multicenter study conducted at 19 sites across the United States. Eligible patients were adults 18 years of age or older with high-risk NMIBC who had not received prior intravesical BCG or had received BCG that was stopped more than 3 years before study entry. Patients were also required to have high-risk tumors, defined as stage T1, high-grade or G3 disease, or carcinoma in situ (CIS).

All enrolled patients received durvalumab at 1500 mg intravenously every 4 weeks for 13 cycles, combined with BCG induction therapy weekly for 6 weeks and BCG maintenance therapy as 3 doses at weekly intervals at 3, 6, 12, 18, and 24 months.

The primary end point was the incidence of grade 3 or 4 AEs possibly related to study treatment that occurred within 6 months of treatment initiation, as assessed by the investigator. Key secondary end points included broader safety and tolerability parameters, including serious AEs, immune-mediated AEs, AEs resulting in treatment interruption or discontinuation, and laboratory findings.

What were the baseline characteristics?

Patients were enrolled onto the study between August 2023 and December 2024, with a data cutoff of June 30, 2025, and a median follow-up for safety of 10.8 months (Q1, Q3: 8.0-14.3).

Of 132 patients screened, 99 received treatment. At the data cutoff, 73 patients were ongoing on any study treatment, 88 were ongoing in the study, and 26 had discontinued both durvalumab and BCG. Eleven patients terminated the study due to patient withdrawal (n = 5), death (n = 2), loss to follow-up (n = 1), or other reasons (n = 3).

In the treated population, the median age was 70.0 years (Q1, Q3: 64.0-77.0); 27% of patients were younger than 65 years, 37% were aged 65 years to younger than 75, and 35% were 75 years of age or older. The majority of patients were male (86%), White (93%), had an ECOG performance status of 0 (90%), had CIS (62%), and had papillary tumors (92%). Regarding tumor stage, 49%, 43%, and 8% of patients had T1, Ta, and CIS-only disease, respectively.

What additional safety data were reported from this analysis?

Any AE was reported in 94% of patients in the overall safety population (n = 99). Maximum grade 3/4 AEs occurred in 29% of patients, 16% of which were possibly related to any study treatment, 15% of which were possibly related to durvalumab, and 3% of which were possibly related to BCG.

Any serious AEs were reported in 19% of patients. Maximum grade 3/4 AEs occurred in 17% of patients, 6% of which were possibly related to any study treatment, 5% of which were possibly related to durvalumab, and 1% of which were possibly related to BCG. Of note, 1 patient experienced a serious AE of myocardial infarction unrelated to study treatment.

Treatment discontinuation due to any AE occurred in 23% of patients; of these, 21% were possibly related to any study treatment, 18% were possibly related to durvalumab, and 4% were possibly related to BCG.

Any PRAEs to any study treatment were reported in 83% of patients. By system organ class and individual event, the most common (≥10%) PRAEs were as follows:

• Renal and urinary disorders: 44%, including dysuria (24%), pollakiuria (22%), hematuria (16%), and micturition urgency (14%)
• General disorders and administration site conditions: 35%, including fatigue (29%) and chills (10%)
• Skin and subcutaneous tissue disorders: 26%, including rash (12%)
• Gastrointestinal disorders: 23%, including diarrhea (12%)
• Musculoskeletal and connective tissue disorders: 23%, including arthralgia (10%)

No unexpected AEs were reported with durvalumab plus BCG.

What immune-mediated AEs were observed?

Any-grade immune-mediated AEs (imAEs) were reported in 20% of patients in the overall safety population, with maximum grade 3/4 imAEs in 5% of patients. At the data cutoff, imAEs had resolved in 6 of 20 patients (30%) who experienced any imAE, and 42% of reported imAE events had resolved.

The most common imAE was hypothyroidism (any grade, 9%; grade 3/4, 0%). Other imAEs of note included hyperthyroidism (2%; 0%), thyroiditis (2%; 0%), increased blood thyroid-stimulating hormone levels (2%; 0%), maculopapular rash (2%; 1%), arthralgia (2%; 0%), autoimmune nephritis (1%; 1%), colitis (1%; 1%), pancreatitis (1%; 1%), diabetic ketoacidosis (1%; 1%), and type I diabetes mellitus (1%; 0%).

Hypothyroidism, maculopapular rash, arthralgia, autoimmune nephritis, colitis, pancreatitis, and diabetic ketoacidosis led to treatment discontinuation in 1 patient each. Systemic corticosteroid intervention was required for hypothyroidism (1%), maculopapular rash (2%), arthralgia (2%), autoimmune nephritis (1%), colitis (1%), and pancreatitis (1%).

What is the significance of these data?

Tyson concluded by stating that the primary safety data from PATAPSCO support the further evaluation of durvalumab plus BCG in BCG-naive, high-risk NMIBC and build on the DFS benefit previously demonstrated in the phase 3 POTOMAC trial (NCT03528694). Updated data from POTOMAC, which were concurrently presented at this year’s AUA Annual Meeting, showed that durvalumab plus BCG induction and maintenance therapy reduced the risk of high-risk disease recurrence or death by 32% vs BCG alone (HR, 0.68; 95% CI, 0.50-0.93; P = .0154) at a median follow-up of 60.7 months and 24% DFS maturity.²

Disclosures: Tyson reported consulting fees from Astellas, AstraZeneca, enGene, Ferring, ImmunityBio, Protara, and UroGen. The PATAPSCO study was funded by AstraZeneca. Medical writing and editorial support were provided by Emma Beddie, BSc(Hons), of Parexel International, funded by AstraZeneca.

References

1. Jayram G, Shore ND, Tyson MD, et al. Durvalumab in combination with bacillus Calmette-Guérin for bacillus Calmette-Guérin-naïve, high-risk non-muscle-invasive bladder cancer: primary results from a US-based, phase 3b, open-label, single-arm, multicenter study (PATAPSCO). Presented at: 2026 AUA Annual Meeting; May 15–18, 2026; Washington, DC.
2. Shore ND, Nishiyama H, Palou Redorta J, et al. Durvalumab in combination with BCG induction and maintenance therapy for BCG-naive, high-risk non–muscle-invasive bladder cancer: expanded efficacy and safety analyses from POTOMAC. Presented at: 2026 American Urological Association Annual Meeting; May 15-18, 2026; Washington, DC.