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Benjamin P. Saylor is associate editor of Urology Times, an Advanstar Communications publication.

Articles

Total detection rate was 36% (13/36) in the ultra-low PSA group and 51% (47/93) in the low-PSA group. 

Piflufolastat F 18 yields high detection rate even at low PSA levels for prostate cancer

professor and vice chair of urology at Wake Forest University in Winston-Salem, North Carolina, is a co–editor in chief for 

"Sometimes, there is more than a single answer to a question; this certainly applies to patients with benign prostatic disease," writes Gopal H. Badlani, MD.

SoBPD: How many ways can you treat BPH or BPD?

Robert J. Motzer, MD, reported that median PFS was 16.4 months in the nivolumab plus cabozantinib arm (95% CI, 12.5-19.3) vs 8.3 months in the sunitinib arm (95% CI, 7.0-9.7) (HR=0.58, 95% CI, 0.49-0.70). 

Final CheckMate 9ER data show long-term efficacy of nivolumab/cabozantinib in RCC

The results encompassed the first 100 patients enrolled in the registry.

Real-world data show impact of piflufolastat F18 on prostate cancer management 

Urology Times is the leading resource for urologists & allied health professionals offering clinical analysis, policy perspectives, & practical advice.

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"I'm hopeful that the decisions are more informed in terms of actual science," says Daniel Kwon, MD.

Daniel Kwon, MD, discusses study’s impact on veteran access to germline testing for prostate cancer

"Whenever they discuss germline testing, an important part of that is this pretest counseling process where you talk about the pros and the cons," says Daniel Kwon, MD.

Discussing germline testing for prostate cancer with veterans

"[Veterans] may be missing out on potentially life-saving treatments, and their family might also be missing out on some benefits as well," says Daniel Kwon, MD.

Germline testing study’s implications for veteran access to prostate cancer treatments

"We were trying to understand how veterans were making decisions about germline testing for their prostate cancer," says Daniel Kwon, MD.

Daniel Kwon, MD, on germline testing for prostate cancer in veterans with service-connected benefits

Dr. De La Cerda provides an overview of a patient case involving a 68 year-old male presenting with severe back pain, with an analysis of the clinical presentation, workup, and medical history.

Bone Predominant mCRPC Patient Case

Video content above is prompted by the following:

What are your initial impressions of the case?

Video Series

The FDA has accepted a Biologics License Application (BLA) seeking approval of nivolumab (Opdivo) co-formulated with Halozyme’s proprietary recombinant human hyaluronidase (rHuPH20), or subcutaneous nivolumab, for the treatment of patients with all previously approved solid tumor indications for nivolumab as a monotherapy, monotherapy maintenance following completion of combination therapy with nivolumab plus ipilimumab (Yervoy), or in combination with chemotherapy or cabozantinib (Cabometyx).

Nivolumab is currently approved under several indications, including in combination with ipilimumab for the first-line treatment of patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC), in combination with cabozantinib for the first-line treatment of patients with advanced RCC, for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy, and in combination with cisplatin and gemcitabine for the first-line treatment of patients with unresectable or metastatic urothelial carcinoma.

The FDA is set to have a decision regarding the subcutaneous nivolumab formulation on or by December 29, 2024.

 According to a news release from Bristol Myers Squibb,

 approval of the formulation would make it the first and only subcutaneously administered PD-1 inhibitor.

“We believe subcutaneous nivolumab has the potential to make a significant difference in the lives of patients, which is reinforced by the FDA’s acceptance of our application,” said Gina Fusaro, PhD, vice president, global program lead, Bristol Myers Squibb, in the news release.

 “Opdivo is a foundational PD-1 inhibitor approved for many different types of cancer, and our continued investment in research that puts patients first remains a priority. If approved by the FDA, the subcutaneous administration of nivolumab would provide patients and their physicians with a new option that delivers the same well-known benefits as IV Opdivo but with the improved convenience of an injection administered in 3 to 5 minutes rather than a 30-to-60-minute infusion.”

The BLA submission is supported by findings from the phase 3 CheckMate-67T trial (NCT04810078), in which subcutaneous nivolumab met the study’s co-primary end points by demonstrating noninferiority to intravenous (IV) nivolumab regarding time average nivolumab serum concentration over 28 days (C

; geometric mean ratio [GMR}, 2.098; 90% CI, 2.001-2.200) and minimum serum concentration at a steady state (C

Data from the study, which were presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California,

 also showed that subcutaneous nivolumab demonstrated noninferiority to IV nivolumab in the key powered secondary end point of objective response rate (ORR). Specifically, the subcutaneous arm demonstrated an ORR of 24.2% (95% CI, 19.0-30.0) per blinded independent central review (BICR), compared with 18.2% (95% CI, 13.6-23.6) in the IV arm.

The safety profile for subcutaneous nivolumab was consistent with that of the IV formulation. Among patients who received the subcutaneous formulation, 8.1% experienced injection-site reactions, with all being low-grade and transient. Deaths due to study drug toxicity occurred in 3 patients in the subcutaneous arm and 1 patient in the IV arm. Most deaths that occurred during the study were due to disease progression.

In total, the phase 3, open-label CheckMate-67T trial enrolled 495 patients with advanced or metastatic ccRCC who had received prior systemic therapy. Patients were randomly assigned 1:1 to receive 1200 mg subcutaneous nivolumab plus rHuPH20 every 4 weeks (n = 248) or to 3 mg/kg IV nivolumab every 2 weeks (n = 247) for up to 2 years of treatment or until disease progression, unacceptable toxicity, withdrawal, or death.

The co-primary pharmacokinetic end points for noninferiority testing were C

 of subcutaneous nivolumab vs IV nivolumab. The key secondary end point was ORR per BICR.

Final completion of the CheckMate-67T study is expected in January 2026.

1. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 6, 2024. Accessed May 7, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Accepts-Bristol-Myers-Squibbs-Application-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx

2. Bristol Myers Squibb announces updated action date by the U.S. Food and Drug Administration for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Published online and accessed May 21, 2024. https://investors.bms.com/iframes/press-releases/press-release-details/2024/Bristol-Myers-Squibb-Announces-Updated-Action-Date-by-the-U.S.-Food-and-Drug-Administration-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx

3. George S, Bourlon TB, Chacon MR, et al. Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Pharmacokinetics (PK), efficacy, and safety results from CheckMate 67T. 

4. A study of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread (CheckMate-67T). ClinicalTrials.gov. Last updated March 1, 2024. Accessed May 7, 2024. https://clinicaltrials.gov/study/NCT04810078

The FDA is set to have a decision regarding the subcutaneous nivolumab formulation on or by December 29, 2024. 

News

FDA accepts BLA for subcutaneous nivolumab in solid tumors

Treatment of metastatic castration-resistant prostate cancer (mCRPC) with the investigational agent mevrometostat (PF-06821497) in combination with enzalutamide (Xtandi) appears to confer benefit for patients, according to data to be presented this week at the 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco, California.

Investigators, led by Michael Schweizer, MD, associate professor of medical oncology at Fred Hutchinson Cancer Center in Seattle, Washington, reported that the treatment combination was associated with median radiographic progression-free survival (rPFS) of 14.3 months vs 6.2 months with enzalutamide alone.

In their abstract, the investigators reported, “Dose exploration of mevrometostat + enzalutamide [plus] androgen deprivation therapy (ADT) showed a manageable safety profile with evidence of EZH2 pharmacodynamic inhibition, objective response (OR), and decline in prostate-specific antigen of ≥50% from baseline (PSA

) in patients with mCRPC (NCT03460977).” At ASCO GU, the authors presented data from an open-label, randomized, dose-expansion component of the study.

Patients with mCRPC were eligible for inclusion in the study if they had received prior abiraterone acetate (Zytiga), 1 or fewer prior chemotherapy in any setting, and had evidence of progression as defined by modified Prostate Cancer Clinical Trials Working Group 3 criteria. The cohort, which was receiving androgen deprivation therapy, was randomly assigned 1:1 to receive oral mevrometostat 1250 mg twice daily on an empty stomach plus enzalutamide 160 mg once daily or to enzalutamide, stratified by prior chemotherapy.

The study’s primary end points were rPFS per investigator assessment as well as safety. Secondary end points included objective response by RECIST 1.1, PSA

A total of 81 patients were included in the study; 41 received mevrometostat plus enzalutamide and 40 received enzalutamide alone. Median follow-up was 9.6 months (interquartile range, 3.1-14.5 months). Median patient age was 70 years (range, 48-86 years) for the combination group and 71.5 years (range, 50-86 years) for the enzalutamide-alone group. The investigators reported that 43.9% of patients in the combination group and 45.0% of patients in the enzalutamide-alone group had received prior taxane therapy.

According to the data presented at ASCO GU, the OR rate in patients who had measurable disease at baseline (15 patients in the combination group and 14 patients in the enzalutamide group) was 26.7% (95% CI: 7.8-55.1) for the combination group and 14.3% (range, 1.8-42.8) for the enzalutamide-alone group. The investigators observed a confirmed PSA

 in 34.1% (95% CI: 20.1-50.6) of patients in the combination group and 15.4% (95% CI: 6.0-31.3) for the enzalutamide-alone group.

Regarding safety, the most common treatment-emergent adverse events (TEAEs) in the combination group included diarrhea (78.0%), decreased appetite (58.5%), and dysgeusia (58.5%). The most common TEAEs in the enzalutamide-alone group included asthenic conditions (42.5%), nausea (25.0%), and anemia (22.5%). Grade 3 or higher TEAEs were observed in 53.7% of patients in the combination group vs 42.5% in the enzalutamide-alone group.

According to a news release from Pfizer, mevrometostat is an “investigational selective inhibitor of enhancer of zeste homolog 2.” The company also noted that it has “initiated 2 pivotal phase 3 trials for mevrometostat plus [enzalutamide] in 2024 and expects to start a phase 3 study of mevrometostat plus [enzalutamide] in first-line mCSPC [metastatic castration-sensitive prostate cancer] during the first half of 2025.”

1. Schweizer M, Calvo M, Moreno V, et al. Mevrometostat (PF-06821497), an enhancer of zeste homolog 2 (EZH2) inhibitor, in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC): a randomized dose-expansion study. Presented at: American Society of Clinical Oncology Genitourinary Cancers Symposium; February 13-15, 2025; San Francisco, California. Abstract LBA138. https://meetings.asco.org/abstracts-presentations/243221

2. Pfizer to showcase advancements across genitourinary cancers at ASCO GU Cancers Symposium. News release. Pfizer. January 28, 2025. Accessed February 12, 2025. https://www.businesswire.com/news/home/20250127366998/en/Pfizer-to-Showcase-Advancements-Across-Genitourinary-Cancers-at-ASCO-GU-Cancers-Symposium

The investigational agent mevrometostat, combined with enzalutamide, shows promise in treating metastatic castration-resistant prostate cancer (mCRPC), as evidenced by improved median radiographic progression-free survival (rPFS) compared to enzalutamide alone. The study, involving 81 patients, demonstrated a manageable safety profile and significant pharmacodynamic inhibition of EZH2. The combination therapy resulted in higher objective response rates and prostate-specific antigen declines. Common adverse events included diarrhea and decreased appetite. Pfizer has initiated phase 3 trials for this combination, aiming to explore its efficacy in first-line metastatic castration-sensitive prostate cancer.

The treatment combination was associated with median radiographic progression-free survival of 14.3 months vs 6.2 months with enzalutamide alone.

Mevrometostat/enzalutamide combo shows rPFS benefit in mCRPC

Additional follow-up data from the phase 3 EV-302 trial (also known as KEYNOTE-A39; NCT04223856) continued to show that the combination of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda; EV+P) provides benefit in median overall survival (OS) and progression-free survival (PFS) vs chemotherapy in patients with locally advanced or metastatic urothelial carcinoma (la/mUC).

These results, conducted at a median follow-up of 29.1 months, are consistent with the OS and PFS benefits that were seen at the primary analysis of the trial, presented in October 2023.

The updated analysis was presented by primary investigator Thomas Powles, MD, PhD, at the 

2025 American Society of Clinical Oncology Genitourinary Cancers Symposium

“These latest findings from the EV-302 trial reaffirm the primary results, which demonstrated survival improvements for patients treated with enfortumab vedotin and pembrolizumab that were previously unprecedented in locally advanced or metastatic urothelial cancer,” said Powles, a professor of genitourinary oncology at Queen Mary University of London and director of the Barts Cancer Center in London, England, in a news release on the findings.

 “These data show that the potential survival benefit has become even more robust with extended follow up and further solidify the combination as standard of care.”

Overall, the combination of EV+P reduced the risk of death by 49% vs chemotherapy, with a median OS of 33.8 months (95% CI, 26.1-39.3) with the combination vs 15.9 months (95% CI, 13.6-18.3) with chemotherapy (HR, 0.51; 95% CI, 0.43-0.61). Additionally, the median PFS was 12.5 months (95% CI,10.4-16.6) for EV+P vs 6.3 months (95% CI, 6.2-6.5) for chemotherapy, translating to a 52% reduction in the risk of disease progression or death (HR, 0.48; 95% CI, 0.41-0.57).

Powles noted during the presentation, “The forest plot analysis for [PFS] and [OS] shows benefit irrespective of upper tract disease, liver metastases, PD-L1 expression, platinum eligibility, presence of metastatic disease, and renal function.”

The data also showed an OS benefit with EV+P regardless of cisplatin eligibility. Among the cisplatin-eligible patients, the median OS was 36.7 months (95% CI, 31.5-not estimable) with EV+P compared with 18.7 months (95% CI, 16.6-22.1) with chemotherapy (HR, 0.54; 95% CI, 0.42-0.70). Among those who were cisplatin ineligible, the median OS was 25.6 months (95% CI, 22.7-36.1) and 12.7 months (95% CI, 11.0-14.7), respectively (HR, 0.50; 95% CI, 0.39-0.64).

Regarding the trial’s secondary end points, the confirmed objective response rate (cORR) was 67.5% in the combination arm compared with 44.2% in the chemotherapy arm. The median duration of response was 23.3 months (95% CI, 17.8-not estimable) and 7.0 months (95% CI, 6.2-9.0), respectively.

Further, 30.4% of patients in the combination arm and 14.5% of patients in the chemotherapy arm achieved a confirmed complete response (cCR). The median duration of cCR was not reached in the EV+P arm and was 15.2 months (95% CI, 10.3-not estimable) in the chemotherapy arm.

The safety profile was consistent with the primary analysis from the EV-302 trial, and no new safety signals emerged. In total, 57.3% of patients in the combination arm and 69.5% of patients in the chemotherapy arm experienced a grade 3 or higher treatment-related adverse event (TRAE). In the cCR subgroup, TRAEs of grade 3 or higher occurred in 61.7% and 71.9% of patients, respectively.

Treatment-related deaths occurred in 1.1% of patients treated with the combination vs 0.9% treated with chemotherapy. No treatment-related deaths occurred in the cCR subgroup.

In total, the EV-302 trial enrolled 886 patients with la/mUC who were randomly assigned 1:1 to receive EV+P (n = 442) or chemotherapy (n = 444). In the treatment arm, patients received 1.25 mg/kg of IV EV on days 1 and 8 plus 200 mg of IV pembrolizumab on day 1. In the chemotherapy arm, patients received either gemcitabine with cisplatin or carboplatin every 3 weeks.

The co-primary end points were OS and PFS per blinded independent central review. Secondary end points including cORR, duration of response, and safety. According to the authors, “An exploratory analysis evaluated treatment outcomes and safety in [patients] with cCR.”

The combination of EV+P was approved in the US in April 2023 for the treatment of patients with la/mUC. The combination also has approvals in this indication in the European Union, Japan, and other countries around the world.

“In conclusion, after 2.5 years of median follow-up, we continue to show a compelling benefit for EV+P over chemotherapy. [The] median overall survival of 34 months [is] unprecedented compared to what we saw before,” Powles concluded in his presentation. “These data reinforce enfortumab vedotin and pembrolizumab as the new standard of care in frontline urothelial cancer.”

1. Powles T, Van Der Heijden M, Loriot Y, et al. EV-302: Updated analysis from the phase 3 global study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (chemo) in previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC). 

. 2025;43(suppl 5). Abstract 664. doi:10.1200/JCO.2025.43.5_suppl.664

2. Pfizer and Astellas’ PADCEV (enfortumab vedotin-ejfv) plus KEYTRUDA (pembrolizumab) shows long-term efficacy in first-line treatment of locally advanced or metastatic urothelial cancer (la/mUC). News release. Pfizer. February 10, 2025. Accessed February 15, 2025. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-astellas-padcevr-enfortumab-vedotin-ejfv-plus-0

“These data reinforce enfortumab vedotin and pembrolizumab as the new standard of care in frontline urothelial cancer," says Thomas Powles, MD, PhD.

EV/pembrolizumab continues to show OS, PFS benefit vs chemotherapy in la/mUC

Findings from WOLVERINE, a global meta-analysis of several randomized trials, suggest that metastasis-directed therapy (MDT) confers benefits in several survival-related outcomes in oligometastatic prostate cancer.

“Although there exists more prospective randomized data for oligometastatic prostate cancer, the data investigating metastasis-directed therapy is limited to generally several smaller phase 2 trials. Much has been hypothesized regarding patient subgroups who do or do not benefit from metastasis-directed therapy, but these analyses are limited. Finally, the current phase 2 randomized trials that do exist have spanned several eras in metastatic prostate cancer imaging and treatment. Thus, we sought to pool the existing data in the X-MET collaboration, which is meant to amalgamate all randomized investigating oligometastatic solid tumors,” explained Chad Tang, MD, BS, MS, associate professor of radiation oncology at the University of Texas MD Anderson Cancer Center in Houston, at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California.

Tang and his colleagues identified all published trials that randomly assigned patients with oligometastatic prostate cancer (fewer than 5 metastases) to MDT and standard of care (SOC) vs SOC alone. Individual patient data were pooled, with progression-free survival (PFS), radiographic PFS (rPFS), castration-resistance free survival (CRFS), and overall survival (OS) harmonized across studies. The investigators conducted 2 parallel analyses: a meta-analysis using common and random effect models to calculate pooled HRs and a Cox regression that incorporated individual patients who were stratified by trial enrollment.

Contributing studies included ARTO (NCT03449719), STOMP (NCT01558427), COMET (NCT01446744), EXTEND (intermittent and continuous cohorts, NCT03599765), and ORIOLE (NCT02680587). A total of 472 patients with oligometastatic prostate cancer were included. Median follow-up was 41 months. Patients were randomly assigned to MDT plus SOC (n = 248) or SOC alone (n = 224). A total of 125 (50%) patients in the MDT plus SOC group received a second-generation androgen receptor pathway inhibitor compared with 134 (60%) patients in the SOC alone group. Fifty-two (21%) patients in the MDT plus SOC group received androgen deprivation therapy alone compared with 40 (18%) in the SOC alone group. Median number of metastases was 2 for each group.

Regarding PFS, in the trial-level analysis, the HR was 0.44 (95% CI, 0.35-0.57; 

< .0001). Median PFS was 35 months in the MDT plus SOC group vs 21 months in the SOC alone group. In the Cox regression analysis, the HR was 0.45 (95% CI, 0.35-0.58; 

< .0001). For rPFS, the HR for trial-level analysis was 0.60 (95% CI, 0.43-0.85; 

= .0039), the HR for the Cox regression analysis was 0.59 (95% CI, 0.46-0.76; 

< .0001). For CRFS, the HR for the trial-level analysis was 0.58 (95% CI, 0.37-0.92; 

= .019), and the HR for the Cox regression analysis was 0.58 (95% CI, 0.37-0.91; 

= .020). Median CRFS was 72 months in the MDT plus SOC group vs 63 months in the SOC alone group. For OS, the HR for the trial-level analysis was 0.63 (95% CI, 0.39-1.004; 

= .051), and the HR for the Cox regression analysis was 0.64 (95% CI, 0.40-1.01; 

= .057). The 48-month OS was 87% in the MDT plus SOC group vs 75% in the group receiving SOC alone.

“In summary, across the different end points, the pooled analysis of all published trials randomizing oligometastatic prostate cancer to MDT vs not in addition to standard of care systemic therapy or observation reveal an improvement in [PFS] and later end points…MDT benefit was maintained across subgroups, including patients who had do novo presentations and thus untreated primaries, independent of the different staging modalities used across studies, independent of castration-sensitive and resistant status, and independent of whether the patient was treated with or without ADT,” Tang said.

1. Tang C, Sherry AD, Hwang H, et al. World-wide oligometastatic prostate cancer (omPC) meta-analysis leveraging individual patient data (IPD) from randomized trials (WOLVERINE): an analysis from the X-MET collaboration. 

 2025;43(suppl 5). Abstract 15. doi:10.1200/JCO.2025.43.5_suppl.15

A global meta-analysis, WOLVERINE, evaluated the impact of metastasis-directed therapy (MDT) on oligometastatic prostate cancer, revealing significant benefits in survival outcomes. The study pooled data from several randomized trials, comparing MDT plus standard of care (SOC) to SOC alone. Results showed improved progression-free survival (PFS), radiographic PFS, and castration-resistance free survival (CRFS) with MDT. The analysis included 472 patients, with a median follow-up of 41 months. The findings suggest MDT's efficacy across various patient subgroups, regardless of staging modalities or androgen deprivation therapy (ADT) use.

Median PFS was 35 months in the MDT plus SOC group vs 21 months in the SOC alone group. 

WOLVERINE findings highlight benefits of MDT in oligometastatic prostate cancer

The FDA has authorized an expanded access program (EAP) to provide an alternative source of BCG, recombinant BCG (rBCG), to patients across the US, ImmunityBio announced in a news release.

According to the company, the hope is that this program will help to address the ongoing shortage of TICE BCG in the US. The shortage, which ramped up in 2019, has posed challenges for the treatment of patients with non–muscle invasive bladder cancer (NMIBC), for which BCG has been the standard of care since 1977. In the release, ImmunityBio cited a recent survey of 100 urologists, of which 57% reported they were unable to treat patients in the previous 12 months due to a lack of access to TICE BCG.

There is currently only one manufacturer of TICE BCG in the US. For this EAP, ImmunityBio has partnered with the Serum Institute of India, which develops rBCG, to provide an alternative source across the country. According to the news release, these shipments are set to begin immediately.

“With the increasing threat of supply shortages of essential medicines, the biopharmaceutical industry must innovate and secure new means of ensuring uninterrupted access to vital therapeutics,” said Patrick Soon-Shiong, MD, founder, executive chairman, and global chief scientific and medical officer of ImmunityBio, in the news release.

 “Our collaboration with the FDA and Serum Institute to ensure a reliable supply of this vital drug for bladder cancer patients underscores ImmunityBio’s commitment to addressing critical access issues that affect so many patients.”

Following the FDA's approval of nogapendekin alfa inbakicept-pmln (Anktiva) in April 2024, ImmunityBio announced the collaboration with the Serum Institute of India to supply the company with standard BCG, as well as rBCG, to be used in combination with Anktiva in its approved indication.

 The supply of BCG through this partnership is now available through the EAP across the US.

The rBCG vaccine (VPM1002BC) has been evaluated in phase 1/2 clinical trials in Europe as an immunotherapy in patients with NMIBC.

 According to ImmunityBio, rBCG has 2 gene modifications that enable improved immunogenicity and safety vs other formulations of BCG. In clinical trials, the rBCG vaccine has already shown favorable safety and tolerability as well as enhanced immunogenicity in driving CD8+ and CD4 T cells compared with earlier strains of BCG, the company reported.

Specifically, the phase 1/2 trial of the therapy, conducted in patients with NMIBC who had failed conventional BCG, showed that 49.3% (95% CI, 32.1-64.4%) of patients treated with VPM1002BC remained recurrence-free at 1 year following treatment.

At 2- and 3-year follow-up, the recurrence-free rates were 47.4% (95% CI, 30.4-62.6%) and 43.7% (95% CI 26.9-59.4%), respectively.  

The therapy was also found to be safe and generally well tolerated. Grade 1, 2, and 3 treatment-related adverse events occurred in 14.3%, 54.8%, and 4.8% of patients, respectively. No grade 4 adverse events were reported. In total, 2 of 42 patients were not able to complete 5 or more instillations during the induction period.

Data on rBCG is also available from studies assessing it as a tuberculosis (TB) vaccine. These studies include 2 trials in healthy adult participants, 1 in healthy newborn infants, and a trial in HIV-unexposed and HIV-exposed, BCG-naive newborn infants. Studies have also been conducted to assess “the effect of rBCG vaccination on TB recurrence and on the susceptibility or severity of respiratory diseases during the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) pandemic,” ImmunityBio noted.

1. FDA authorizes ImmunityBio to provide recombinant BCG (rBCG) to urologists to address TICE BCG shortage. News release. ImmunityBio. February 19, 2025. Accessed February 19, 2025. https://ir.immunitybio.com/news-releases/news-release-details/fda-authorizes-immunitybio-provide-recombinant-bcg-rbcg

2. ImmunityBio, Serum Institute of India agree on an exclusive arrangement for global supply of Bacillus Calmette-Guerin (BCG) across all cancer types. News release. ImmunityBio. May 2, 2024. Accessed February 19, 2025. https://ir.immunitybio.com/news-releases/news-release-details/immunitybio-serum-institute-india-agree-exclusive-arrangement

3. Rentsch CA, Bosshard P, Mayor G, et al. Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy. 

. 2020;9(1):1748981. doi:10.1080/2162402X.2020.1748981

4. Rentsch CA, Thalmann GN, Lucca I, et al. A phase 1/2 single-arm clinical trial of recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC immunotherapy in non-muscle-invasive bladder cancer recurrence after conventional BCG therapy: SAKK 06/14. 

The FDA has approved ImmunityBio's Expanded Access Program to provide recombinant BCG (rBCG) as an alternative to TICE BCG, addressing the US shortage impacting non–muscle invasive bladder cancer (NMIBC) treatment. ImmunityBio collaborates with the Serum Institute of India to distribute rBCG, which has shown improved immunogenicity and safety in clinical trials. The partnership also supports the use of rBCG with Anktiva, following its FDA approval. Ongoing trials continue to evaluate rBCG's efficacy in bladder cancer and other conditions, including tuberculosis.

According to ImmunityBio, shipments of rBCG are set to begin immediately via the EAP. 

Daniel Kwon, MD

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