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

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Larry Lipshultz, MD, is a professor of Urology and chief of the Scott Department of Urology's Division of Male Reproductive Medicine and Surgery at Baylor College of Medicine.

Discover groundbreaking insights in urology as Larry Lipshultz, MD, shares innovative research and strategies for male fertility challenges.

Pearls & Perspectives: Innovation in male fertility care with Larry Lipshultz, MD, at AUA 2025

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

In patients with low-grade intermediate-risk non–muscle invasive bladder cancer (NMIBC) treated with reverse thermal gel containing mitomycin (UGN-102) who achieved a complete response (CR) at 3 months, an 18-month duration of response of 80.6% was observed.

Updated data from the phase 3 ENVISION trial (NCT05243550) were reported at the 

2025 American Urological Association (AUA) Annual Meeting

“This is low-grade, intermediate-risk non–muscle invasive bladder cancer. The reason why this is so important for urologists is this is a highly recurrent, persistent cancer that recurs despite many of the types of treatments that we utilize. The standard of care for this is TURBT [transurethral resection of the bladder tumor]. But by definition, these tumors typically recur and so TURBT, with or without adjuvant treatment, remains [an] inadequate treatment for this,” explained lead ENVISION investigator Sandip M. Prasad, MD, MPhil, director of Genitourinary Surgical Oncology and vice chair of urology at Morristown Medical Center/Atlantic Health System, New Jersey.

A total of 240 patients were enrolled in the study to receive treatment with UGN-102. “The mean size of the tumors was 2.5 cm, and 83% of these tumors are multifocal,” Prasad said. The treatment was administered in the office via traditional catheter with 1 treatment per week for 6 weeks. Ninety-five percent of patients received all 6 doses.

“For the 5% that did not receive all 6 doses, the majority received 5, so almost all patients can complete the entire treatment course,” Prasad said.

The primary end point was CR at 3 months, which was achieved in 79.6% of patients.

“At 18 months, for patients who were complete responders, the Kaplan-Meier estimate for remaining a complete responder, meaning event free for the entire period, was over 80%. This is very unusual, and I think probably the most notable aspect of this study is that we're seeing durability of response that exceeds what we typically know for TURBT. This makes sense based on the treatment. When we do TURBT, we have to resect what we can see, and we know based on blue light cystoscopy and narrow band imaging that we have limitations in how well we do TURBT. These treatments are agnostic. The gel coats the entirety of the urinary lining, and some of the recurrences that we probably see at 3 months, 6 months and 9 months are just tiny tumors we didn't see initially, but the gel would treat those, because you don’t have to see anything; it coats every part of it. Therefore, the durability makes sense from the mechanism of how this drug works,” Prasad commented.

Regarding safety, adverse events reported with UGN-102 treatment included dysuria, hematuria, urinary tract infection, pollakiuria, and fatigue.

“There were 2 patients out of 240 that had a treatment-related severe adverse event. One was urethral stenosis, 1 was urinary retention. Both were resolved,” Prasad said.

“In conclusion, we see a very robust and clinically meaningful 80% complete response rate in patients with recurrent low-grade disease at 3 months. We see a very high probability of maintaining that complete response 18 months later, without maintenance treatment…and I would argue that UGN-102 may very well represent a well-tolerated alternative to TURBT as primary treatment for patients with low-grade disease,” Prasad said.

In a news release about the results, UroGen Pharma Chief Medical Officer Mark Schoenberg, MD, said, "The duration of response data from the ENVISION trial further underscores UGN-102’s potential to positively impact the treatment landscape for patients with recurrent LG-IR-NMIBC. Many of these patients are elderly and face the burden of repeated surgeries under general anesthesia, highlighting the urgent need for innovative treatment options. If approved, we believe UGN-102’s potential to deliver durable complete responses, reduce recurrence rates, and extend treatment-free intervals would represent a significant advancement in the management of recurrent LG-IR-NMIBC."

1. Prasad SM, Shiskov D, Vmihaylov N, et al. Treatment of recurrent low-grade intermediate-risk non-muscle invasive bladder cancer with UGN-102: ongoing results from a single-arm, open-label, phase 3 trial (ENVISION).

2025;213(5S):e387. doi:10.1097/01.JU.0001109848.08748.9e.01

2. UroGen announces updated 18-month duration of response (DOR) of 80.6% from the phase 3 ENVISION trial of UGN-102, an investigational treatment for recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). News release. UroGen Pharma. April 26, 2025. Accessed April 27, 2025. https://www.businesswire.com/news/home/20250426951270/en/UroGen-Announces-Updated-18-Month-Duration-of-Response-DOR-of-80.6-from-the-Phase-3-ENVISION-Trial-of-UGN-102-an-Investigational-Treatment-for-Recurrent-Low-Grade-Intermediate-Risk-Non-Muscle-Invasive-Bladder-Cancer-LG-IR-NMIBC

UGN-102, a reverse thermal gel containing mitomycin, demonstrated an 80.6% 18-month duration of response in patients with low-grade intermediate-risk non–muscle invasive bladder cancer (NMIBC) who achieved a complete response at 3 months. The phase 3 ENVISION trial highlighted the treatment's potential as a well-tolerated alternative to TURBT, offering durable responses without maintenance therapy. The study involved 240 patients, with a primary endpoint of a 79.6% complete response rate at 3 months. Adverse events were generally mild, with only two severe cases reported.

"I would argue that UGN-102 may very well represent a well-tolerated alternative to TURBT as primary treatment for patients with low-grade disease,” says Sandip M. Prasad, MD, MPhil.

UGN-102 positions itself as an alternative to TURBT for low-grade NMIBC

The first patients have been enrolled in a phase 2 trial (NCT05413850) evaluating the safety and anti-tumor activity of (177Lu) rhPSMA-10.1 injection for metastatic castration-resistant prostate cancer (mCRPC).

"This is an important step forward in the development of Lutetium (177Lu) rhPSMA-10.1 injection and builds on the strong data seen in the phase 1 clinical trial,” said David Gauden, DPhil, CEO of Blue Earth Therapeutics, in a news release.

 “Commencement of treatment of patients at full intended therapeutic dosing levels provides a great opportunity to assess the benefit this therapy can bring to patients. With up to 20 sites enrolling patients, we expect to see first results from the study early next year. We are grateful to the physicians and patients of Biogenix Molecular in Florida, who have just recruited the first patients for the study."

In total, the study plans to enroll 82 patients across both the phase 1 and phase 2 portions of the study. Participants will be enrolled through clinical trial sites across the US and the Netherlands.

The phase 2 study will enroll patients who have progressed following at least 1 novel androgen axis drug but have not received prior taxane-based chemotherapy.

To be eligible for enrollment, patients need to have a serum testosterone level less than 50 ng/dL, an ECOG performance score of 0 to 2, a life expectancy of at least 6 months, and adequate bone marrow reserve and organ function, among other criteria.

According to Blue Earth Therapeutics, the design of the study is in line with the FDA’s Project Optimus initiative, where the goal is to front-load radioactivity in earlier treatment cycles.

The company noted, “The study is testing multiple dosing regimens that focus on delivering higher radiation doses when tumor burden is usually highest, at the beginning of treatment. This approach contrasts to pivotal studies of earlier radioligand therapies where the same dose was administered in every cycle regardless of tumor burden.”

Patients in the study will either receive a higher loading dose in the first 2 treatment cycles or have a shorter time between the administration of the first 3 doses, moving from 3 weeks rather than the usual 6 weeks.

The primary outcome measure is the number of patients with an antitumor response, defined as at least a 50% reduction in prostate-specific antigen level from baseline. The study is also assessing radiographic progression-free survival and safety.

According to Blue Earth, initial study results may be available as soon as the first half of 2026.

Phase 1 data on (177Lu) rhPSMA-10.1 injection

Final results from the phase 1 portion of the study showed encouraging radiation dosimetry results with lutetium (177Lu)-rhPSMA-10.1 injection in patients with mCRPC.

In the trial, radiation dosimetry was performed for up to 3 cycles of treatment with 177Lu-rhPSMA-10.1 injection. The study included 13 patients with mCRPC. Overall, the results demonstrated a favorable ratio between radiation doses absorbed in the tumor vs the dose delivered to key healthy organs, such as the kidneys and salivary glands.

Specifically, the mean tumor-to-kidney ratio was 32, and the mean tumor-to-salivary gland ratio was 73. The median absorbed radiation dose to tumors was 8.9 Gy for each GBq administered radioactivity, compared with a mean absorbed radiation dose of 0.27 Gy/GBq in the kidneys and 0.13 Gy/GBq in the salivary glands.

Additionally, the mean biological half-life in tumors was 338 hours. According to the company, “When paired with the 6.7-day physical half-life of 177Lu, this gives an effective mean half-life of 91.4 hours. This allows delivery of radiation to tumors over many days: one and a half to twice the reported data for established agents in this class.”

1. Blue Earth Therapeutics initiates phase 2 clinical trial evaluating the efficacy and safety of Lutetium (177Lu) rhPSMA-10.1 Injection in metastatic castrate resistant prostate cancer. News release. Blue Earth Therapeutics Ltd. May 1, 2025. Accessed May 6, 2025. https://www.prnewswire.com/news-releases/blue-earth-therapeutics-initiates-phase-2-clinical-trial-evaluating-the-efficacy-and-safety-of-lutetium-177lu-rhpsma-10-1-injection-in-metastatic-castrate-resistant-prostate-cancer-302441668.html

2. Anti-tumour activity of (177Lu) rhPSMA-10.1 injection. ClinicalTrials.gov. Last updated March 20, 2025. Accessed May 6, 2025. https://clinicaltrials.gov/study/NCT05413850

3.Blue Earth Therapeutics reports key results from Lutetium (177Lu) rhPSMA-10.1 injection phase 1 clinical trial. News release. Blue Earth Therapeutics Ltd. March 13, 2025. Accessed May 6, 2025. https://www.prnewswire.com/news-releases/blue-earth-therapeutics-reports-key-results-from-lutetium-177lu-rhpsma-10-1-injection-phase-1-clinical-trial-302400601.html

A phase 2 trial is underway to evaluate the safety and anti-tumor activity of (177Lu) rhPSMA-10.1 injection for metastatic castration-resistant prostate cancer (mCRPC). The trial, involving 82 patients across the US and the Netherlands, follows promising phase 1 results. It aims to assess the efficacy of higher radiation doses in early treatment cycles, aligning with the FDA's Project Olympus initiative. The primary outcome is a significant reduction in prostate-specific antigen levels. Initial results are anticipated by early 2026, with phase 1 data showing favorable radiation dosimetry.

Initial study results may be available as soon as the first half of 2026.  

Phase 2 trial launches of (177Lu) rhPSMA-10.1 injection in mCRPC

Use of the Cxbladder Triage test appears to significantly decrease utilization of cystoscopy and imaging in patients who are identified as low risk, according to data presented at the 

2025 American Urological Association Annual Meeting

The results were presented by Christopher Filson, MD, MS, a urologist at Kaiser Permanente in Los Angeles, California.

According to the investigators, Cxbladder Triage “uses mRNA biomarkers and clinical information to classify a patient’s risk of having bladder cancer.” Kaiser Permanente – Southern California (KP-SCAL) utilizes a validated Hematuria Risk Index (the standard of care [SOC]) to guide both the use of cystoscopy as well as type of imaging modality. For the study at AUA 2025, the investigators sought to evaluate “real-world utility of adding the Cxbladder Triage test to the standard KP-SCAL microscopic hematuria diagnostic workflow.”

Patients were included in the study if they had a urinalysis with microscopic hematuria, had an encounter with a urologist between September 2021 and September 2024, were between 38 and 88 years of age, and had 6 months of membership with Kaiser Permanente before and after the encounter. Patients were excluded if they had gross hematuria within 6 months prior to the encounter or had a prior diagnosis of bladder cancer. The investigators identified patients who underwent testing with Cxbladder Triage and created a 1:1 matched cohort of non-tested patients based on the date of the encounter and hematuria risk index.

Based on their Cxbladder Triage test result, patients were divided into 2 groups: low probability of bladder cancer (<4.00) and physician-directed protocol (≥4.00). Outcomes of interest for the study included cystoscopy within 6 months, CT urography within 6 months, and bladder cancer diagnosis within 6 months and 1 year.

“Of 5242 patients who received the Cxbladder Triage test, 3,353 (64%) were included for analysis and matched 1:1 with SOC patients,” the investigators wrote. Mean age (standard deviation) was 61.3 (12.4) years in the Cxbladder Triage arm and 62.1 (12.9) years in the SOC arm. More than half of patients were female in both cohorts.

The investigators reported that 2670 patients had a low probability score in the Cxbladder Triage and SOC groups, and that 683 patients had physician-directed protocol. The 6-month CT urogram rate was 7.5% (201 patients) in the low probability patients receiving CxBladder Triage and 11.7% (313 patients) in the low probability patients receiving SOC. The 6-month CT urogram rate was 19.5% (133 patients) in the physician-directed protocol patients receiving Cxbladder Triage and 13.3% (91 patients) in the physician-directed protocol patients receiving SOC. The 6-month bladder cancer rate was 0.1% (3 patients) in the low probability patients receiving Cxbladder Triage and 0.7% (19 patients) in the low probability patients receiving SOC. The 6-month bladder cancer rate was 2.5% (17 patients) in the physician-directed protocol patients receiving Cxbladder Triage and 0.6% (4 patients) in the physician-directed protocol receiving SOC. The 1-year bladder cancer rate was 0.1% (3 patients) in the low probability patients receiving Cxbladder Triage and 0.7% (19 patients) in the low probability patients receiving SOC. The 1-year bladder cancer rate was 2.6% (18 patients) in the physician-directed protocol patients receiving CxBladder Triage and 0.7% (5 patients) in the physician-directed protocol receiving SOC.

All told, the study population was able to avoid 952 cystoscopies and 70 CT scans, according to the investigators.

“Cxbladder Triage testing significantly decreased cystoscopy and imaging utilization among low-risk microscopic hematuria patients while simultaneously increased use among higher-risk patients. Further population-level evaluations of the Cxbladder Triage test are warranted to reduce the burden of unnecessary cystoscopy,” the investigators wrote in their poster.

In a news release about the study, Pacific Edge Chief Executive Peter Meintjes, PhD, said, “The Kaiser Permanente study is important because it demonstrates the real-world impact of Cxbladder Triage with tremendous statistical power given the sample size of 3353 patients. The design of the study prospectively managed hematuria patients according to the new Triage-based standard of care and then retrospectively compared those clinical outcomes to a cohort of 'risk-matched' patients from Kaiser Permanente nation-wide EMR who did not. This kind of study and evidence generation is uniquely available in the Kaiser Permanente system and underscores the value of our partnership and our shared commitment to improving patient outcomes.”

AUA 2025 also featured discussion of the organization’s recent microhematuria guideline, which “specifically mentions Cxbladder Triage as the only urine-based biomarker test that has ‘Grade A’ evidence from a randomized controlled trial — the STRATA Study,

 which demonstrated the test can reduce cystoscopies by up to 59% without compromising tumor detection,”according to the news release.

1. Filson C, Loo RK, Slezak JM, Jhaveri J, Aboushwareb T, et al. Clinical utility of a urinary biomarker (Cxbladder Triage) compared to standard of care for microscopic hematuria evaluations in a large independent delivery network. 2025;213(5S):e246. doi:10.1097/01.JU.0001109788.99555.df.11

2. Cxbladder's clinical utility in focus at AUA 2025. News release. Pacific Edge. April 23, 2025. Accessed April 28, 2025. 

https://www.pacificedgedx.com/news-and-events/news/2025/cxbladders-clinical-utility-in-focus-at-aua-2025/

3. Lotan Y, Daneshmand S, Shore N, et al. A multicenter prospective randomized controlled trial comparing cxbladder triage to cystoscopy in patients with microhematuria: the safe testing of risk for asymptomatic microhematuria trial. 2024;212(1):41-51. doi:10.1097/JU.0000000000003991

The Cxbladder Triage test, utilizing mRNA biomarkers, significantly reduces the need for cystoscopy and imaging in low-risk patients with microscopic hematuria, as demonstrated in a study by Kaiser Permanente. The study, involving 3,353 patients, showed a marked decrease in cystoscopy and CT scan utilization among low-risk patients, while higher-risk patients saw increased use. The findings underscore the test's potential to optimize diagnostic workflows and reduce unnecessary procedures. The study's design and outcomes highlight the value of integrating Cxbladder Triage into standard care practices.

The study population was able to avoid 952 cystoscopies and 70 CT scans, according to the investigators.

Cxbladder Triage may help patients avoid unnecessary cystoscopies

The CD46-targeting antibody-drug conjugate (ADC) FG-3246 (formerly FOR46) demonstrated encouraging clinical activity while maintaining a manageable safety profile in patients with metastatic castration-resistant prostate cancer (mCRPC), according to data from a phase 1 trial (NCT03575819).

“I am excited to see the results from the phase 1 monotherapy study of FG-3246 published in the 

,” said lead author Rahul Aggarwal, MD, a professor of medicine at the University of California, San Francisco, in a news release on the findings.

 “This is the first clinical trial targeting CD46 in patients with prostate cancer, and the totality of the data highlights the promising potential of FG-3246 anti-cancer activity, especially when considering the unselected, heavily pre-treated patient population in the trial. The trial results provide key insights into the potential clinical impact of targeting CD46 in the treatment of mCRPC and support its further development in this disease space with high unmet need.”

In total, the study enrolled 56 patients with mCRPC across both the dose escalation and dose expansion phases. The maximum tolerated dose was determined to be 2.7 mg/kg, using adjusted body weight, every 3 weeks.

According to the authors, “Dose-limiting toxicities included neutropenia (n = 4), febrile neutropenia (n = 1), and fatigue (n = 1).”

Across all dose levels, the most frequently reported grade 3 or higher adverse events were neutropenia (59%), leukopenia (27%), lymphopenia (7%), anemia (7%), and fatigue (5%). Grade 3 febrile neutropenia was also observed in 1 patient. No treatment-related deaths were reported.

A total of 40 patients were evaluable for efficacy, which was defined as patients with adenocarcinoma who received a dose of 1.2 mg/kg or higher. In these patients, the median radiographic progression-free survival (rPFS) was 8.7 months (range, 0.1 to 33.9). A prostate-specific antigen (PSA) decline of at least 50% (PSA50) was observed in 36% of patients (14 of 39). A PSA50 response was also noted among 4 of 8 (50%) patients who received docetaxel in the castrative-sensitive setting.

Additionally, 25 patients were included in the RECIST-evaluable set. Among those patients, the confirmed objective response rate was 20%, with all objective responses observed among patients who received a dose of 2.7 mg/kg or higher. The median duration of response was 7.5 months.

Further, the disease control rate was 80%. The duration of treatment was longer than 24 weeks in 48% (12) of patients.

Immunohistochemistry showed that 12 of 15 (80%) evaluable baseline tumors were positive for CD46 expression. Patients who responded to treatment with FG-3246 were found to have a significantly higher frequency of effector T cells as well as a lower frequency of immunosuppressive myeloid cells.

Overall, the first-in-human, open-label phase 1 trial enrolled 56 patients with mCRPC across 5 clinical trial sites in the US.

Those enrolled were biomarker unselected and heavily pretreated, with a median of 5 lines of prior therapy.

The dose-escalation phase of the trial included 33 patients who received FG-3246 at doses ranging from 0.1 mg/kg and 3.0 mg/kg intravenously every 3 weeks. The dose-expansion phase included 23 patients, of whom 18 had adenocarcinoma mCRPC (cohort 1) and 5 had neuroendocrine prostate cancer (cohort 2). Patients in the dose-expansion phase received FG-3246 at the dose level of 2.7 mg/kg using adjusted body weight to a maximum of 270 mg for every 3 weeks.

Primary outcome measures included dose-limiting toxicities and disease response.

“We are looking forward to advancing FG-3246 in the clinic and remain on track for initiating the phase 2 monotherapy study by mid-2025 as well as disclosing topline results from the combination trial of FG-3246 and enzalutamide in the second half of 2025,” said Thane Wettig, CEO of FibroGen, in the news release.

 “FG-3246 represents a potential first-in-class, non-PSMA approach to treating mCRPC and we, along with the medical community, are excited about the potential for CD46 to become a next generation target in the prostate cancer treatment paradigm.”

1. Aggarwal RR, Vuky J, VanderWeele D, et al. Phase I, first-in-human study of FOR46 (FG-3246), an immune-modulating antibody-drug conjugate targeting CD46, in patients with metastatic castration-resistant prostate cancer. 

. 2025:JCO2401989. doi:10.1200/JCO-24-01989

FG-3246, a CD46-targeting antibody drug conjugate, showed promising clinical activity and a manageable safety profile in a phase 1 trial for metastatic castration-resistant prostate cancer (mCRPC). The trial enrolled 56 heavily pre-treated patients, determining a maximum tolerated dose of 2.7 mg/kg every three weeks. Notable adverse events included neutropenia and fatigue, but no treatment-related deaths occurred. Efficacy was observed with a median radiographic progression-free survival of 8.7 months and a 36% PSA50 response rate. The trial supports further development of FG-3246 in mCRPC treatment.

The company plans to initiate the phase 2 monotherapy trial by mid-year. 

Larry Lipshultz, MD

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