Kristie L. Kahl

The FDA has approved TLX591-CDx (trade name, Illuccix), a radiopharmaceutical cold kit for the preparation of gallium-68 (

Ga) gozetotide (also known as PSMA-11) injection.

Ga PSMA-11 was previously approved by the FDA as the first drug for PET-imaging of PSMA-positive lesions in men with prostate cancer.

Ga PSMA-11 is indicated for patients with suspected metastasis who are eligible for initial definitive therapy, or patients with suspected recurrence due to an elevated PSA level.

 cyclotrons or in nuclear pharmacies and healthcare centers across the country using Eckert & Ziegler’s GalliaPharm®generator or IRE ELIT’s Galli Eo® generator. This optionality, along with a four-hour shelf life after radiolabeling with 

Ga, enables Illuccix to flexibly extend the reach of advanced PSMA-PET imaging to patients across the country,” Telix, the manufacturer of TLX591-CDx, explained in a news release.

Commenting on the approval in the news release, A. Oliver Sartor, MD, Medical Director at Tulane Cancer Center, stated, “The approval of Illuccix will give patients considerably improved access to PSMA-PET imaging, an advanced diagnostic tool that was recently included in the NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer. With patient doses able to be prepared on-site or via commercial radiopharmacy networks, either via generator or cyclotron, Illuccix delivers flexible patient scheduling and on-demand access throughout the day.”

The FDA approved 68Ga PSMA-11 based on the safety and efficacy of the treatment proven in 2 prospective clinical trials with a total of 960 men with prostate cancer who each received 1 injection of the drug.

In the first trial, 325 patients who were candidates for surgical removal of the prostate gland and pelvic lymph nodes and were considered at higher risk for metastasis underwent PET/CT or PET/MRI scans performed with Ga 68 PSMA-11. Of the patients who went on to undergo surgery, Ga 68 PSMA-11 PET demonstrated a clinically important rate of metastatic cancer confirmed by surgical pathology in patients with positive readings in the pelvic lymph nodes.

In the second trial, 635 patients who had rising serum PSA levels after initial prostate surgery or radiotherapy, 74% had at least 1 positive lesion detected by Ga 68 PSMA-11 PET in at least 1 body region. In total, 91% of patients with positive Ga 68 PSMA-11 PET readings who had correlative tissue pathology from biopsies, who also had results from baseline or follow-up imaging by conventional methods, and serial PSA levels available for comparison, also had local recurrence or metastasis of prostate cancer confirmed.

Christian Behrenbruch, PhD, managing director and CEO at Telix, shared his thoughts on the approval of TLX591-CDx in the news release: “This heralds a new era of patient and physician access to gallium-based PSMA-PET imaging and marks an important new stage for Telix as we bring our first commercial product to market in the United States,” “Improved imaging can provide physicians with the insights to determine the most appropriate treatment pathway and give patients in the U.S. access to a specific and sensitive imaging tool for the detection of prostate cancer throughout the body.”

1. FDA Approves Telix’s Prostate Cancer Imaging Product, Illuccix. Published online December 20, 2021. Accessed December 20, 2021. https://bit.ly/3J8Wgan

2. FDA approves first PSMA-targeted PET imaging drug for men with prostate cancer. Press release. FDA. December 1, 2020. Accessed December 1, 2020. https://bit.ly/3fWUOcN

Articles

TLX591-CDx (Illuccix) is a radiopharmaceutical cold kit for the preparation of gallium-68 PSMA-11 injection.

FDA approves novel PSMA-PET imaging product for prostate cancer

Treatment with nivolumab (Opdivo) continued to induce improved disease-free survival (DFS) among patients with high-risk muscle-invasive urothelial carcinoma (MIUC) following radical surgery, regardless of previous treatment with neoadjuvant chemotherapy, nodal involvement, or PD-L1 status, according to extended follow-up from the phase 3 Checkmate 274 trial (NCT02632409) presented at the 22nd Annual Meeting of the Society of Urologic Oncology.

“With longer follow-up, nivolumab continued to demonstrate a clinically meaningful improvement in disease-free survival versus placebo for patients with high-risk muscle invasive urothelial cancer after radical surgery. This disease-free survival benefit was observed in both the intent to treat [ITT] population and in the subset of patients with tumors harboring high levels of PD-L1 expression, a disease-free survival benefit with nivolumab was observed in most pre-specified clinical subgroups,” Matthew Galsky, MD, professor of medicine (hematology and medical oncology); director of genitourinary medical oncology; co-director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute; and associate director for translational research at The Tisch Cancer Institute at Mount Sinai, said during a virtual presentation of the poster.

The randomized, double-blind, multicenter phase 3 CheckMate 274 trial enrolled a total of 709 patients with high-risk MIUC, originating in the bladder, ureter, or renal pelvis, including 353 in the ITT nivolumab group (PD-L1 ≥1%, n = 140) and 356 in the placebo group (PD-L1 ≥1%, n = 142). Additionally, 140 patients in the nivolumab arm and 142 in the placebo arm had a PD-L1 expression of 1% or more.

Patients were randomized 1:1 and stratified based on PD-L1 expression, pathological nodal status, and treatment with a neoadjuvant cisplatin-based chemotherapy. A dose of 240 mg of nivolumab or placebo was administered every 2 weeks intravenously for up to a year or until disease recurrence or trial discontinuation.

The primary end point of the study was DFS for all patients in the ITT population, as well as those with a PD-L1 expression of 1% or greater. The key secondary end point was NUTRFS in the ITT population and in patients with PD-L1 ≥1%. Moreover, DMFS was an exploratory end point. DFS was also evaluated in prespecified subgroups.

To be eligible for the trial, the high-risk population of patients with MIUC who had previously undergone radical surgery needed to have undergone radical surgery with or without cisplatin-based chemotherapy within 120 days prior to randomization, and were required to have an ECOG performance status of 0 or 1.

Following a previous minimum follow-up in the ITT population of 5.9 months, DFS was significantly improved with nivolumab, compared with placebo, both in the ITT population (HR, 0.70; 98.22% CI, 0.55-0.90; 

 <.001) and in the population with tumor PD-L1 expression ≥1% (HR, 0.55; 98.72% CI, 0.35-0.85; 

 < .001). The safety profile of nivolumab was consistent with that observed in previous trials.

Following an additional follow-up of 5 months, which included a minimum follow-up in the intention-to-treat (ITT) population of 11 months (median follow-up in the nivolumab vs placebo group, 24.4 months vs 22.5 months, respectively) and 11.4 months in the PD-L1 ≥1% group (median follow-up in the nivolumab vs placebo group, 25.5 months vs 22.4 month), DFS benefit with nivolumab was maintained.

With the longer follow-up, the anti-PD-1 antibody demonstrated improved DFS, compared with placebo, in the ITT nivolumab and placebo groups (22.0 months vs 10.9 months, respectively), as well as in the PD-L1 ≥1% groups (not reached [NR] vs 8.4 months). DFS probability at 12 months was 63.5% with nivolumab and 46.9% with placebo in ITT patients, and 67.6% vs 46.3%, respectively, among patients with PD-L1 ≥1%.

In the subgroup analysis, improved DFS was observed with nivolumab, compared with placebo, for those in subgroups including age (<65: HR, 0.73; 95% CI, 0.53-1.01), sex (female: HR, 0.77, 95% CI, 0.50-1.17), ECOG performance status (1: HR, 0.79; 95% CI, 0.56-1.12), nodal status (N0/x with <10 nodes removed: HR, 0.85; 95% CI, 0.57-1.27), use of prior cisplatin-based chemotherapy (No: HR, 0.90; 95% CI, 0.68-1.18), and PD-L1 status (<1%: HR, 0.82; 95% CI, 0.63-1.05).

At 12 months, non-urothelial tract recurrence-free survival (NUTRFS) probabilities were also improved with nivolumab, versus placebo, in both the ITT (65.8% vs 50.6%, respectively) and PD-L1 ≥1% (69.2% vs 47.1%) populations. The median NUTRFS in the ITT was 26.0 months [95% CI, 19.5-41.1] vs 13.7 months [95% CI, 8.4-20.0]; HR, 0.71; 95% CI, 0.58-0.88), respectively, and placebo (NR [95% CI, 25.8-not estimable (NE)] vs 10.8 months [95% CI, 5.7-20.7]; HR, 0.54; 95% CI, 0.39-0.77) groups was also improved with nivolumab.

Similarly, median distant metastasis-free survival (DMFS) was also improved with nivolumab, compared with placebo, in both the ITT (41.1 months [95% CI, 26.0-NE] vs 29.3 months [95% CI, 15.2-NE], respectively; HR, 0.73; 95% CI, 0.58-0.92) and PD-L1 ≥1% groups (NR [95% CI, 26.0-NE] vs 20.7 months [95% CI, 10.8-NE]; HR, 0.60; 95% CI, 0.41-0.88).

In terms of time to response, the median among the nivolumab and placebo groups, respectively, were 25.8 months (95% CI, 19.6-NE) and 11.1 months (95% CI, 8.3-19.4) in the ITT population, and NR (95% CI, 25.8-NE) and 10.9 months (95% CI, 5.8-22.2) in the PD-L1 ≥1% population.

Galsky added that subsequent systemic therapy was received by 30% of patients on the nivolumab arm and 37.6 patients on the placebo arm.

The median duration of therapy was 10.1 months (range, 0-12.5) in the nivolumab group, compared with 8.6 months (range, 0-12.6) in the placebo group.

“These results support adjuvant nivolumab as a standard of care for patients with high-risk muscle-invasive urothelial cancer after radical resection,” Galsky said.

1. Galsky MD, Witjes JA, Gschwend JE, et al. Disease-free survival with longer follow-up from the phase 3 Checkmate 274 trial of adjuvant nivolumab in patients who underwent surgery for high-risk muscle-invasive urothelial carcinoma. Presented at: SUO 22nd Annual Meeting; December 1-3, 2021; Orlando, Florida. Poster 175.

2. Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. 

. 2021;384(22):2102-2114. doi:10.1056/NEJMoa2034442.

According to extended follow-up from the phase 3 Checkmate 274 trial, nivolumab continued to demonstrate improved disease-free survival in patients with high-risk muscle-invasive urothelial carcinoma.

Longer follow-up shows improved DFS with nivolumab in high-risk muscle-invasive urothelial carcinoma

The PET agent targeting prostate specific membrane antigen (PSMA) 

F-DCFPyL effectively detected recurrent lesions in prostate cancer patients with biochemical recurrence (BCR), according to a single center study presented at the 2021 American Urological Association Annual Meeting.

“It is well known that prostate cancer is No. 1 as far as new cases in men in the United States and second only after lung cancer as far as estimated deaths for the same year. So, we need better imaging tools,” Andrei Iagaru, MD, professor of radiology-nuclear medicine, chief, Division of Nuclear Medicine and Molecular Imaging, Stanford Health Care, said during a virtual presentation at the meeting.

In total, 242 patients were prospectively enrolled with biochemical recurrence after primary definitive treatment with prostatectomy (72%), radiotherapy (28%), or both (25%).

In total, 131 patients (54%) had a Gleason score of 7.

Among those who underwent radical prostatectomy and radiation therapy, respectively, the median times to first BCR were 34 months (range, 3-240) and 48 months (range, 3-192). Mean 

F-DCFPyL activity was 343.0±25.2 MBq, and time to acquisition after administration was 77.3±13.2 minutes.

F-DCFPyL based on PSA level (ng/mL) in patients who experienced BCRwere as follows: PSA <0.5, 65%; 0.5≤ PSA <1, 74%; 1≤ PSA <2, 90%; 2 ≤ PSA < 5, 93%; and PSA ≥ 5, 96%. Across all PSA levels, the detection rate was 81%. Among patients who underwent prostatectomy, the corresponding detection rates of 

F-DCFPyL by the same PSA ranges, respectively, were 65%, 73%, 90%, 96%, and 100%. Across all PSA levels the detection rate post-prostatectomy was 80%. And after radiotherapy, the corresponding detection rates were 100%, 100%, 100%, 88%, and 94%, respectively, with a detection rate of 92% across all PSA levels.

Further, researchers evaluated the detection rate of 

F-DCFPyL after prostatectomy based on PSA doubling time. After the first 3 months, 90% showed a positive scan, compared with 86% from months 3 through 6, 75% from months 6 through 12, and 61% for month 12 and beyond.

“Of course, the more aggressive the tumor, the lower the doubling time, the higher the positivity rate. And similarly, if we look at Gleason score, the more aggressive the tumor, the higher the percentage of positivity rate,” Iagaru said. “Now, whereas this positivity was just not unexpected, that number is higher in the prostate gland after radiation therapy. But then once you get into lymph nodes, and bones and other organs, the numbers are pretty similar between the 2 groups.”

F-DCFPyL PET/CT,46% on targeted radiotherapy, 28% on androgen-deprivation therapy, 8% on surveillance, and 18% considered “other,” changed management of their disease after a positive scan, compared with 24%, 7%, and 69%, respectively, who changed treatment management after a negative scan.

F-DCFPyL PET/CT holds great potential to be a ‘one-stop shop’ diagnostic tool in the work-up of BCR prostate cancer to identify possible extra-pelvic oligometastases for locally targeted therapy,” the researchers concluded in their abstract.

1. Song H, Nguyen J, Moradi F, et al. Prospective Evaluation of 

F-DCFPyL PET/CT in Biochemically Recurrent Prostate Cancer: analysis of 18F-DCFPyL uptake in possible extra-pelvic oligometastases. Presented at: 2021 American Urologic Association Annual Meeting; September 10-13, 2021; Virtual. Abstract LBA-02-06.

The PET agent targeting prostate specific membrane antigen (PSMA) 18F-DCFPyL effectively detected recurrent lesions in prostate cancer patients with biochemical recurrence.

18F-DCFPyL may be “one-stop shop” in detecting recurrence in prostate cancer with BCR

Induction therapy combining avelumab (Bavencio) and BCG appeared to be safe and well tolerated in patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC), according to the phase 1b ABC Trial, presented during the 2021 American Urological Association Annual Meeting.

“We know that BCG installation causes a systemic immune response as measured by increased urinary cytokines and serum cytokines that occurs around 4 weeks into induction therapy. We also know that immunotherapy has a time bearing clearance based on pharmacokinetics,” Kelly Stratton, MD, urologic oncologist, Stephenson Cancer Center, University of Oklahoma, explained during a virtual presentation at the meeting.

The aim of the study was to evaluate the optimization of immunotherapy in patients with NMIBC who may require novel dosing regimens linked to BCG administration.

In the trial, patients received induction BCG therapy, followed by maintenance BCG therapy for up to 12 months. At each BCG treatment, patients also received an avelumab infusion. When patients were not receiving BCG, they received avelumab infusions every 2 weeks.

The primary end point of the study was to complete a full induction course within 8 weeks of patients starting treatment, defined as at least 5 of 6 treatments of BCG plus avelumab. Secondary end points included tolerability, measured by the 6-month completion rate (completion of at least 2 of 3 maintenance treatments within a 5-week period at 6 months); 3- and 6-month CR rates; recurrence-free survival; cystectomy-free survival; and overall survival.

Key inclusion criteria consisted of histologically or cytologically documented NMIBC; BCG unresponsive; ECOG performance score of 0 to 2; aged 18 years or older; life expectancy of weeks or more; adequate hematologic and end-organ function; evidence of locally advanced or metastatic bladder cancer; evidence of extravesical bladder cancer; active central nervous system metastases; prior treatment with a PD-L1 inhibitor; and prior radiation to the bladder.

Median age was 70 years (range, 53-84). The majority of patients were male (78%), White (89%), and had T1 stage disease (n = 9).

“This was a heavily pretreated group, with 8 patients receiving multiple BCG induction treatments, and 4 patients previously enrolled on the SWOG 1602 trial,” Stratton said.

In total, 15 of 18 patients (83%) completed induction therapy, 16 patients received at least 5 BCG treatments, and 15 patients received at least 5 avelumab treatments, which exceeded the 60% anticipated completion rate, Stratton said.

At the 3-month cystoscopy, 13 of 15 patients (87%) remained on treatment, 10 of 15 (67%) experienced a complete response (CR), and 3 of 15 had persistent disease.

In addition, 5 patients (28%) have completed 12 months of treatment—all with CRs, and 2 patients remain on treatment.

Serious adverse events (AEs) occurred in 3 patients (17%), including 2 grade 3 AEs during induction (infusion reaction and sepsis) and 1 grade 3 AE during maintenance therapy (myasthenia gravis). No treatment-related grade 4/5 AEs were seen.

“This study evaluated induction therapy with combined BCG and avelumab, which appeared safe and well tolerated in BCG, unresponsive, non-muscle invasive bladder cancer patients,” Stratton said. “This study supports continued efforts to evaluate the optimal dosing regimen to synergize BCG and immunotherapy.”

1. Cookson M, Tripathi A, Patel S, et al. Novel Weekly Immunotherapy Dosing with Avelumab Tolerated During Bacillus Calmette-Guerin Induction Therapy: Initial Results of the ABC Trial. Presented at: 2021 American Urologic Association Annual Meeting; September 10-13, 2021; Virtual. Abstract LBA-02-04.

Data from the phase 1b ABC Trial showed that adding avelumab to BCG induction therapy may be safe and well tolerated in patients with BCG-unresponsive non–muscle invasive bladder cancer.



Kristie L. Kahl

Articles

FDA approves novel PSMA-PET imaging product for prostate cancer

Longer follow-up shows improved DFS with nivolumab in high-risk muscle-invasive urothelial carcinoma

18F-DCFPyL may be “one-stop shop” in detecting recurrence in prostate cancer with BCR

Avelumab/BCG induction appears safe, tolerable in BCG-unresponsive NMIBC