ImmunityBio's Anktiva Pursues European and UK Approval for BCG-Unresponsive Bladder Cancer
核心洞察
ImmunityBio's Anktiva, combined with BCG, seeks approval in the EU and UK for treating BCG-unresponsive non-muscle invasive bladder cancer (搜索) (NMIBC (搜索)) with carcinoma in situ (搜索) (CIS (搜索)).
The MAAs submitted to the EMA and MHRA are supported by Phase 2/3 QUILT-3.032 trial data, demonstrating a 71% complete response rate in patients with NMIBC (搜索) with CIS (搜索).
Regulatory assessments by both agencies are anticipated to conclude by Q4 2025, potentially leading to approval in Europe and the UK by 2026, expanding global access.
ImmunityBio is expanding its reach for Anktiva, seeking approval in Europe and the United Kingdom for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (搜索) (NMIBC (搜索)) with carcinoma in situ (搜索) (CIS (搜索)). The company has submitted Marketing Authorization Applications (MAAs) to both the European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency (MHRA) for Anktiva (nogapendekin alfa inbakicept) in combination with Bacillus Calmette-Guérin (BCG). These submissions are based on promising data from the Phase 2/3 QUILT-3.032 trial, potentially offering a new treatment option for patients with limited alternatives.
The EMA covers 27 countries in the EU, as well as Iceland, Norway, and Liechtenstein. The assessment is expected to be complete by the fourth quarter of 2025. Similarly, the UK assessment of the MAA is anticipated to be completed by the fourth quarter of 2025. ImmunityBio is in continued dialog for requests for information from the two agencies, with the potential of approval by 2026.
QUILT-3.032 Trial Results
The MAAs are supported by data from the ongoing Phase 2/3 QUILT-3.032 trial (NCT03022825). As of the data cutoff of July 15, 2024, the complete response (CR) rate with nogapendekin alfa inbakicept plus BCG among the 100 evaluable patients with BCG-unresponsive high-grade NMIBC (搜索) with CIS (搜索) (cohort A) was 71%. In patients with a CR, the duration of response (DOR) ranged from 0.03 months to 54 months and ongoing.
The single-arm, multicenter trial included patients with BCG-unresponsive, high-risk NMIBC (搜索) with CIS (搜索) with or without Ta/T1 papillary disease after transurethral resection. Those with a history of or evidence of muscle invasive, locally advanced, metastatic, and/or extravesical bladder cancer, were excluded. Study participants received nogapendekin alfa inbakicept at 400 mcg with BCG weekly for 6 consecutive weeks in the induction period, followed by once a week, every 3 weeks at 4, 7, 10, 13, and 19 months for those with low-grade or no disease. Those who had persistent CIS or high-grade Ta disease at 3 months were able to have a second course of induction treatment. Those with ongoing CR at 25 months were able to have additional instillations once a week, every 3 weeks at months 25, 31, and 37.
Safety Profile
The safety of nogapendekin alfa inbakicept was examined in cohort A of the trial (n = 88). The median number of doses received was 12 (range, 2-30) and the median duration of exposure was 7.1 months (range, 0.26-36.3). Sixteen percent of patients experienced serious adverse effects (AEs) with the regimen. Thirty-four percent of patients experienced AEs that required dose interruption and 7% experienced AEs that ultimately led to permanent treatment discontinuation. Although dose reductions due to AEs were not permitted for nogapendekin alfa inbakicept, 3.4% of patients required dose reductions of BCG.
The most common all-grade AEs experienced by at least 15% of patients in cohort A who received the regimen were dysuria (32%), hematuria (32%), urinary frequency (27%), micturition urgency (25%), urinary tract infection (UTI; 24%), musculoskeletal pain (17%), chills (15%), and pyrexia (15%). The most common grade 3 or 4 AEs were hematuria (3.4%), UTI (2.3%), and musculoskeletal pain (2.3%).
Expansion into Papillary Indication
ImmunityBio is also planning to submit a supplemental Biologics License Application (sBLA) to the FDA in 2025, seeking approval for Anktiva in patients with BCG-unresponsive NMIBC (搜索) in the papillary indication. This sBLA will be supported by data from cohort B of the QUILT-3.032 trial, which assessed Anktiva in combination with BCG in patients with histologically confirmed BCG-unresponsive high-grade Ta/T1 papillary NMIBC. The median disease-free survival (DFS) was 19.3 months (95% CI, 7.4 to not reached). Per Kaplan Meier estimates, DFS was 55.4% (95% CI, 42% to 66.8%) at 12 months, 51.1% (95% CI, 37.6% to 63.1%) at 18 months, and 48.3% (95% CI, 34.5% to 60.7%) at 24 months.