Nogapendekin Alfa Inbakicept Plus BCG Maintains CR Rate in BCG-Unresponsive NMIBC With CIS

Sebastian Kaulitzki – stock.adobe.com

Treatment with the combination of nogapendekin alfa inbakicept-pmln (N-803; Anktiva) and Bacillus Calmette–Guérin (BCG) continued to generate complete responses (CRs) in patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), according to updated data from the phase 2/3 QUILT-3.032 trial (NCT03022825).¹

In April 2024, prior data from the study supported the FDA approval of N-803 in combination with BCG for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors.²

Updated data announced by ImmunityBio, which were shared in a press release following the enrollment of the 100th patient after the agent’s approval, demonstrated a CR rate of 71% in the expanded patient cohort with the combination; responses ranged to up to 54 months.¹

Data from the study will be submitted to the European Medicines Agency in a marketing authorization application in the fourth quarter of 2024.

“We are encouraged by the consistent CR rates observed in our expanded patient cohort,” Patrick Soon-Shiong, MD, executive chairman and global chief scientific and medical officer of ImmunityBio, stated in a news release. “These results highlight the potential of [N-803] to transform the treatment landscape for patients with BCG-unresponsive NMIBC [with] CIS, offering hope for improved outcomes and cystectomy avoidance, especially with the prolonged duration of response [DOR] now ranging as much as 54 months in this 100-patient analysis. Duration of CR is the key efficacy element in driving cystectomy avoidance in this BCG-unresponsive population. I am pleased that [these] updated [N-803] data confirm that one of the highest durable responses is achieved when compared [with] other approved products in this indication.”

Previously reported data from QUILT-3.032 that supported the FDA approval of the combination showed that the CR rate was 62% (95% CI, 51%-73%).2 The 12- and 24-month DOR rates were 58% and 40%, respectively.

QUILT-3.032 was an open-label, single-arm, multicenter study that enrolled patients at least 18 years of age with histologically confirmed of NMIBC of the transitional cell carcinoma high-grade subtype.3 Notably, patients with mixed histology tumors were allowed to enroll if transitional cell histology was the predominant histology. Patients also needed to have histologically confirmed BCG-unresponsive CIS with or without Ta or T1 disease or BCG-unresponsive high-grade Ta or T1 disease. An ECOG performance status of 0 to 2 was also required.

Investigators excluded patients with recurrence of BCG-unresponsive Ta or T1 disease without the presence of CIS more than 6 months after the last treatment with BCG; BCG-unresponsive CIS more than 12 months after the last BCG instillation; a life expectancy of less than 2 years; or inadequate hematologic, liver, and renal function.

All enrolled patients received BCG and N-803 mixed together in a saline solution before intravesical administration given once per week for 6 weeks as induction therapy. After the first disease assessment, patients received either 3-week maintenance or 6-week re-induction at month 3. Maintenance was allowed to continue in a third treatment period at months 6, 9, 12, and 18, and eligible patients were also allowed to continue maintenance at months 24, 30, and 36.

CR rate and 12-month disease-free survival rates were the trial’s primary end points. Secondary end points included CR rate at different time points.

Study investigators will continue to monitor patients treated in order to assess the durability of responses and overall survival.¹

References

1. ImmunityBio completes Anktiva’s post-approval enrollment of the 100th patient in BCG unresponsive NMIBC CIS trial and reports a complete response rate of 71% with a durable duration of response ranging up to 54 months. News release. ImmunityBio. November 19, 2024. Accessed November 19, 2024. https://www.businesswire.com/news/home/20241119975432/en
2. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. FDA. April 22, 2024. Accessed November 19, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer
3. Quilt-3.032: a multicenter clinical trial of intravesical Bacillus Calmette-Guerin (BCG) in combination with ALT-803 (N-803) in patients with BCG unresponsive high grade non-muscle invasive bladder cancer. ClinicalTrials.gov. Updated April 8, 2024. Accessed November 19, 2024. https://clinicaltrials.gov/study/NCT03022825