Several approvals by the U.S. Food and Drug Administration (FDA) over the past month included therapeutics for patients with BCG-unresponsive non–muscle-invasive bladder cancer and locally advanced rectal cancer.
Nogapendekin Alfa Inbakicept in BCG-Unresponsive NMIBC
On October 14, 2026, the FDA approved the IL-15 receptor agonist nogapendekin alfa inbakicept-pmln (Anktiva) in combination with bacillus Calmette-Guérin (BCG) for the treatment of adults with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC).
This revises a prior indication for adults with BCG-unresponsive NMIBC with carcinoma in situ with or without papillary tumors to include patients with high-grade papillary-only tumors.
QUILT-3.032
Efficacy for the combination regimen was previously demonstrated in Cohort A of the single-arm, multicenter, phase II/III QUILT-3.032 trial (ClinicalTrials.gov identifier NCT03022825), which included 77 patients with BCG-unresponsive, high-risk NMIBC with carcinoma in situ with or without Ta/T1 papillary disease following transurethral resection.
Patients received nogapendekin alfa inbakicept-pmln induction via intravesical instillation with BCG followed by maintenance therapy for up to 37 months. The main efficacy outcome measure was complete response, as determined by cystoscopy, urine cytology, and biopsy. Duration of response was an additional efficacy outcome measure. The complete response rate was 62% (95% confidence interval [CI] = 51%–73%). Fifty-eight percent of patients with a complete response had a duration of response of at least 12 months, and 40% had a duration of response of at least 24 months.
The current approval expands the indication to include patients with BCG-unresponsive high-grade NMIBC with papillary-only tumors based on review of available scientific information.
Although high-grade papillary and carcinoma in situ tumors have different architectural growth features, both are considered aggressive urothelial carcinomas, frequently coexist, can be difficult to distinguish pathologically, and, in the BCG-unresponsive setting, they are associated with high risk for tumor recurrence and progression.
Based on the overlapping clinical and nonclinical features of these two histologic types, the FDA concluded that the prior demonstration of efficacy in patients with BCG-unresponsive NMIBC containing carcinoma in situ could be extrapolated to patients with BCG-unresponsive high-grade papillary disease.
Therefore, the indication for nogapendekin alfa inbakicept-pmln with BCG was expanded to include patients with BCG-unresponsive NMIBC with papillary-only tumors. The FDA is working toward finalizing the Guidance for Industry, “Bacillus Calmette-Guérin–Unresponsive Nonmuscle Invasive Bladder Cancer: Developing Drugs and Biological Products for Treatment” to address this approach.
Safety and Dosage
The most common adverse reactions (≥ 15%), including laboratory test abnormalities, were increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia.
The prescribing information includes a warning that delaying cystectomy can lead to the development of metastatic bladder cancer, which can be lethal.
The recommended dose for nogapendekin alfa inbakicept-pmln is 400 µg administered intravesically with BCG once a week for 6 weeks as induction therapy. A second induction course may be administered if patients have residual carcinoma in situ and/or high-grade Ta tumors at month 3. For maintenance after induction therapy, the recommended dose is 400 µg administered intravesically with BCG once a week for 3 weeks at months 4, 7, 10, 13, and 19 (for a total of 15 doses).
For patients with no evidence of high-grade disease at month 25 and later, maintenance instillations with BCG may be administered once a week for 3 weeks at months 25, 31, and 37 for a maximum of 9 additional instillations. Treatment should be discontinued for disease persistence after second induction, disease recurrence or progression, or unacceptable toxicity. The maximum treatment duration is 37 months.
Dostarlimab for MSI-H/dMMR Locally Advanced Rectal Cancer
The PD-1 inhibitor dostarlimab (Jemperli) received FDA accelerated approval on October 19, 2026, for the treatment of adult patients with stage II/III locally advanced rectal cancer that is microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR), as determined by an FDA-authorized test for solid tumors.
Efficacy for dostarlimab in this indication was evaluated in the multicenter, single-arm, open-label AZUR-1 trial (ClinicalTrials.gov identifier NCT05723562) in 154 patients with previously untreated, histologically confirmed, MSI-H/dMMR, stage II/III locally advanced rectal cancer.
AZUR-1 Trial
Patients received dostarlimab 500 mg intravenously every 3 weeks for 9 cycles, unless unacceptable toxicity or disease progression occurred. Tumor response was assessed using a combination of endoscopy, rectal magnetic resonance imaging (MRI), and computed tomography (CT) scans of the chest, abdomen, and pelvis at week 6 and 12, and at approximately 3 weeks after completing treatment. Patients who achieved a clinical complete response at either of the first two posttreatment assessments entered a nonoperative management period, during which they were closely monitored for recurrence through regular multimodal assessments conducted every 4 months for the first 2 years and every 6 months thereafter. Patients who did not experience clinical complete response, or whose disease recurred or progressed, were evaluated for standard-of-care management at investigator discretion.
The primary efficacy outcome measure was sustained clinical complete response for 12 months per independent central review, measured from the first disease assessment after the last administered dose of dostarlimab where clinical complete response was observed. Additional efficacy outcome measures included investigator assessments of sustained clinical complete response for 12 months and objective response rate by both independent central review and investigator review.
Study Results
Of 154 treated patients, 110 (71%) were treated with dostarlimab alone, did not receive any additional form of treatment, and did not experience disease progression; 26 (17%) underwent surgery (with or without additional systemic therapy or radiation); 13 (8%) received additional systemic therapy or radiation; 1 (0.6%) had progressive disease without further treatment; and 4 (2.5%) withdrew or were lost to follow-up.
In 116 patients evaluable for independent central review, the rate of sustained clinical complete response for 12 months was 47% (95% confidence interval [CI] = 27%–56%). In addition, 38 patients (33%) achieved clinical complete response by independent central review who had less than 12 months of follow-up at the time of the data cut-off, and 44 patients (38%) had a near-complete response.
With a median follow-up of 26.3 months, none of the patients with sustained clinical complete response for 12 months, clinical complete response, or near-complete response experienced disease progression.
The objective response rate per independent central review was 79% (95% CI = 71%–85%). In 144 patients evaluable for investigator assessments, the sustained clinical complete response for 12 months rate was 68% (95% CI = 60%–76%) and the objective response rate was 82% (95% CI = 75%–88%). Of the 15 patients who underwent surgery after dostarlimab alone, based on imaging findings suggesting incomplete response, pathological complete response was reported in 12 patients.
Locally Advanced dMMR Solid Tumors
In addition, the FDA reviewed an investigator-led, multicenter, single-arm, open-label trial (ClinicalTrials.gov identifier NCT04165772) that assessed dostarlimab 500 mg intravenously every 3 weeks for 9 cycles in 50 patients with previously untreated, MSI-H/dMMR, stage II/III locally advanced rectal cancer.
The sustained clinical complete response for 12 months rate was 93% (95% CI = 82%–99%) and the objective response rate was 100% (95% CI = 93%–100%). No patients received chemoradiation and/or rectal cancer surgery as part of the treatment of locally advanced rectal cancer. Of the 27 patients who have been followed for at least 3 years, 1 patient had a local recurrence treated with lymphadenectomy, 1 patient withdrew, and 1 patient died unrelated to disease under study.
Dosage and Safety
The prescribing information includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
The recommended dose for dostarlimab is 500 mg every 3 weeks until disease progression or unacceptable toxicity, for up to nine cycles.
Accelerated Review
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that enables concurrent submission and review among international partners. For this review, FDA collaborated with Health Canada, Israel’s Ministry of Health, Switzerland’s Swissmedic, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies.
This review was also conducted using the Real-Time Oncology Review program, which streamlined data submission prior to the filing of the entire application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 4 months ahead of the FDA goal date.
Pembrolizumab for TMB-H Solid Tumors
On October 16, 2026, the U.S. Food and Drug Administration (FDA) granted traditional approval to pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden–high solid tumors (TMB-H; ≥ 13 mutations/megabase [mut/Mb]), as determined by an FDA-authorized test, in whom disease has progressed following prior treatment and for whom there are no satisfactory alternative treatment options.
Previously, pembrolizumab received an accelerated approval for the treatment of adult and pediatric patients with unresectable or metastatic TMB-H, solid tumors, where TMB-H was defined as ≥ 10 mut/Mb. This approval converts the accelerated approval to traditional approval and amends the TMB-H indication to define TMB-H as ≥ 13 mut/Mb, as efficacy to support traditional approval was not confirmed for patients with a tumor mutational burden of 10 to < 13 mut/Mb.
Efficacy and Safety
Efficacy was evaluated in two groups of patients, the first being Cohort M of the KEYNOTE-158 trial (ClinicalTrials.gov identifier NCT02628067), which prospectively enrolled patients with tumors that were TMB-H and not microsatellite instability-high (MSI-H). Cohorts A through J comprised a prospectively planned retrospective analysis of patients with TMB-H tumors identified within 10 cohorts of patients with various previously treated unresectable or metastatic solid tumors. Patients in Cohorts A through J received pembrolizumab 200 mg every 3 weeks and patients in Cohort M received pembrolizumab 400 mg intravenously every 6 weeks until unacceptable toxicity or documented disease progression.
The major efficacy outcome measures were objective response rate and duration of response in 220 patients with tumors with TMB ≥ 13 mut/Mb (145 in Cohort M and 75 in Cohorts A–J) who received at least one dose of pembrolizumab, as assessed by blinded independent central review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Across both groups, the objective response rate was 36% (95% confidence interval = 30%–43%) and 58% of patients had a duration of response lasting at least 12 months.
The safety profile of pembrolizumab monotherapy for the updated indication was consistent with the known safety profile of pembrolizumab monotherapy.
The prescribing information includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
Recommended Dosage
The recommended dose of pembrolizumab monotherapy for the updated indication is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months. The recommended dose for pediatric patients is 2 mg/kg every 3 weeks (up to a maximum of 200 mg) until disease progression, unacceptable toxicity, or up to 24 months.
This review used the Assessment Aid, a voluntary applicant submission to facilitate the FDA’s assessment.
To learn more about these recent drug approvals, visit FDA.gov.
