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Asymmetric multi-band reflective metasurface for linear and circular polarizations conversion in Ku, K, Ka, and U bands

Abstract This work proposes a novel multi-band reflective metasurface, that is capable of linear polarization (LP), and circular polarization (CP) conversion in Ku, K, Ka, and U Bands. The metasurface design involves a combination of ring and square elements strategically arranged, and printed on a 0.76 mm thin-grounded Rogers RO3003 substrate. The metasurface achieves LP for y-polarized incident electromagnetic (EM) wave in 16.2–17.2 GHz, 23.0–25.4 GHz, 40.3–54.35 GHz frequency bands. The polarization conversion ratio (PCR) for LP frequency ranges is minimum 90% with an fractional bandwidth (FB) of 2.94%, 9.91%, and 26.9%, respectively. Moreover, metasurface achieves CP for y-polarized incident EM wave in 16.1–16.55 GHz, 17.5–22.15 GHz, 26.65–37.75 GHz, and 55.6–59.8 GHz frequency bands. In addition, the axial ratio (AR) for CP frequency ranges is less than 3 dB with a FB of 2.75%, 23.45%, 34.47%, and 7.27%. The device performance is considerably stable under oblique incidences up to 45 degrees. The metasurface unitcell is compact with a structural size of $$\text {length}=0.23\lambda _\circ$$ , $$\text {width}=0.23\lambda _\circ$$ and $$\text {thickness}=0.08\lambda _\circ$$ . The proposed prototype is fabricated, and the measured results are in good agreement with the simulated one. Overall, the proposed metasurface exhibits promising performance characteristics and holds potential for multiple applications in satellite based networks.

Prevalence of adverse events following T-cell engaging bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T-cell therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC): A meta-analysis.

128 Background: T-cell engaging bsAbs and CAR T-cell therapy have shown exceptional success in treating multiple hematologic malignancies. More recently, bsAbs have been FDA-approved to treat uveal melanoma and small cell lung cancer, demonstrating proof-of-concept for immune therapies beyond checkpoint inhibition to effectively treat solid tumors. bsAbs and CAR-T therapies are presently undergoing evaluation in trials for patients with mCRPC. Despite early successes with these classes of therapy, there are multiple ongoing challenges including dose-limiting toxicity, ‘on-target, off-tumor’ toxicity, and immune-effector cell related toxicity. This systematic review analyzes publicly available safety derived from ongoing clinical trials. Methods: An electronic systematic search through PubMed, CINHAL, Scopus, and Ovid was done to identify phase I/II clinical trials evaluating bsAbs or CAR-T therapy in patients with mCRPC reported prior to 9/30/2024. Treatment-related adverse events (TRAE) were collected, focusing on prevalence in bsAbs versus CAR-T. A random effects model was used for analysis. Results: Eleven trials with 511 patients evaluated bsAbs, and 5 trials with 55 patents studied CAR-T therapies. Mean patient age was 67 years [95% CI: 63, 71]. Cytokine release syndrome (CRS) occurred in 49% [24, 75] of patients; 53% [17, 86] on bsAbs compared to 43% [28, 59] on CAR-T. Only 4% [2, 7] of patients had CRS grade ≥3; 14% [2, 43] on CAR-T compared to 3% [2, 6] on bsAbs (p=0.05). Neurologic TRAEs occurred in 11% [3, 31] of patients; 39% [22, 60] on CAR-T compared to 5% [2, 13] on bsAbs (p= <0.01). Hematologic TRAEs occurred in 38% [14, 71] of patients; 34% [8, 75] on CAR-T compared to 43% [9, 86] on bsAbs. Hepatic TRAEs occurred in 31% [12, 59] of patients; 25% [12, 44] on CAR-T compared to 39% [9, 81] on bsAbs (p= 0.55). However, 8% of patients [3, 20] had grade ≥3 hepatic TRAEs, with 21% [5, 51] on CAR-T versus 5% [2, 10] on bsAbs (p=0.03). Musculoskeletal/dermatologic TRAEs were seen in 30% of patients [24, 37]; 30% [24, 38] on bsAbs and 29% [8, 58] on CAR-T (p=0.89). Renal TRAEs occurred in 15% [10, 23] of patients; 21% [5, 51] on CAR-T compared to 14% [8, 24] on bsAbs (p= 0.50). Gastrointestinal TRAEs were reported in 18% [10, 33] of patients; 14% [2, 42] on CAR-T compared to 19% [9, 36] on bsAbs (p= 0.69). Conclusions: In patients with mCRPC, bsAbs and CAR-T therapies produce similar hematological, musculoskeletal/dermatologic, renal and gastrointestinal TRAE rates. However, significantly higher rates of all-grade neurologic, grade ≥3 CRS and grade ≥3 hepatic TRAEs are reported with CAR-T therapy. These data highlight the need to appreciate the differences in toxicity profiles for these two classes of therapy and to practice appropriate vigilance during treatment.

Organ perforation and fistula formation as adverse events in patients receiving tyrosine kinase inhibitors: A post-market analysis.

528 Background: Vascular Endothelial Growth Factor (VEGF)-targeted tyrosine kinase inhibitors (TKIs), such as lenvatinib and cabozantinib, offer significant survival benefits in solid tumors, including renal cell carcinoma (RCC), thyroid cancer, hepatocellular carcinoma, and endometrial cancer. However, rare but serious adverse events (AEs), such as organ perforation and fistula formation, have been reported. This study evaluates the incidence and risk of these events in patients treated with VEGF-TKIs using post-marketing data from the FDA Adverse Event Reporting System (FAERS). Methods: We queried the FAERS database for reports of organ perforation and fistula formation associated with cabozantinib, lenvatinib, axitinib, and tivozanib from January 1, 2012, to June 30, 2024. A disproportionality analysis was performed using reporting odds ratios (ROR) to assess the association between VEGF-TKIs and these adverse events. Cases were categorized by organ site, with a focus on gastrointestinal (GI) tract-related events. Results: We identified 65,194 reports, including 917 cases of organ perforation and 482 cases of fistula formation. Among the perforation cases, 245 (27%) were intestinal, followed by gastric (5%). Fistula cases included 11% anal, 9% female genital tract and 6% were GI-related. Regarding TKI distribution, 19% of perforation cases were linked to cabozantinib, 35% to lenvatinib, and 46% to other TKIs (axitinib, tivozanib, or multiple TKIs). For fistula cases, 18% were associated with cabozantinib, 41% with lenvatinib, and 41% with other TKIs. Among these reports, 27% of perforations and 20% of fistulas occurred in patients with RCC. Disproportionality analysis revealed a significantly higher risk of both organ perforation (ROR: 3.41, 95% CI: 2.36–4.93) and fistula formation (ROR: 17.06, 95% CI: 14.46–20.12) in VEGF-TKI treated patients. Conclusions: Patients treated with VEGF-targeted TKIs, particularly lenvatinib, have a significantly increased risk of organ perforation and fistula formation. Lenvatinib was associated with a higher incidence of these adverse events compared to cabozantinib. These findings highlight the need for increased clinical awareness and monitoring, particularly in patients with RCC. Further research is necessary to better understand the mechanisms underlying these complications and to develop preventive strategies.

Phase 2 study of perioperative sacituzumab govitecan in combination with zimberelimab and domvanalimab for patients with muscle invasive bladder cancer ineligible or who refuse cisplatin-based chemotherapy: The PRISMA-1 study.

TPS884 Background: Neoadjuvant cisplatin-based chemotherapy (NACT) has demonstrated a 5-8% improvement in 5-year overall survival (OS) in patients (pts) with muscle invasive bladder cancer (MIBC). However, its routine implementation is still low due to concerns about toxicity/efficacy. Also, about 50% of pts are considered cisplatin ineligible and therefore unable to receive NACT. Immune-checkpoint inhibitors (ICI) and antibody drug conjugates (ADC) have demonstrated separately clinical activity in the perioperative setting and recently remarkable efficacy of ADC-ICIs combos has been shown in pts with advanced urothelial cancer. Therefore, combining ICIs with ADCs as a neoadjuvant therapy results an interesting approach. PRISMA-1 study will evaluate safety and efficacy of the Trop-2 directed ADC, sacituzumab govitecan (SG) in combination with the anti-PD1 zimberelimab (Z) and the anti-TIGIT domvanalimab (D) in MIBC. This study will also search for predictive biomarkers of response and will evaluate the role of ctDNA in the perioperative setting to better select for patients who need post operative treatment. Methods: PRISMA-1 study (NCT06133517) is a phase II, single arm, multicenter clinical trial that will enroll 70 adult pts with MIBC, [cT2-T4cN0-1cM0], ECOG PS 0-2, non-eligible or who refuse to receive NACT. The primary endpoint is pathological complete response (pCR) rate. Downstaging, relapse free survival and OS along with ctDNA clearance are some of the secondary endpoints. The study has two stages: First 8 pts will receive the combination of neoadjuvant SG+Z to confirm tolerability. Once safety has been confirmed additional 8 pts will receive the triplet SG+Z+D. If no dose limiting toxicities are observed recruitment will continue to enroll a total of 70 patients. Patients will receive three Q3W neoadjuvant cycles of Z (360 mg day 1) + D (1200 mg day 1) plus SG (7.5 mg/m2 days 1 & 8) followed by cystectomy. After surgery, only those pts who do not achieve a pCR or that achieving a pCR still have positive ctDNA will receive 12 additional cycles of adjuvant treatment with only Z + D. The remaining will be followed with serial ctDNA and imaging. Clinical trial information: NCT06133517 .

Oral trehalose improves histological and behavior symptoms of mucopolysaccharidosis type II in iduronate 2-sulfatase deficient mice

Docetaxel rechallenge versus cabazitaxel in patients previously treated with docetaxel for metastatic castrate-resistant prostate cancer (mCRPC).

154 Background: In 2004, docetaxel (DOC), a semi-synthetic taxane, received regulatory approval for mCRPC based on improved overall survival (OS). Cabazitaxel (CAB), a closely related analog of DOC, was approved in 2010 for mCRPC patients previously exposed to DOC. For patients previously treated with DOC, the relative benefits of docetaxel rechallenge (rDOC) versus a taxane switch to CAB are unknown. We aimed to evaluate the relative impact of rDOC versus CAB for patients who had previously received DOC for mCRPC. Methods: This retrospective cohort study compared outcomes of mCRPC patients in the nationwide VA healthcare system who received initial DOC, discontinued DOC for a reason other than disease progression, and later received rDOC or CAB after mCRPC diagnosis. Patients were eligible for inclusion if they received at least 3 cycles of DOC and at least 90 days later received a second course of DOC or CAB. The index date was the date of the start of the second course of taxane treatment. Time-to-event outcomes were evaluated from index date. Inverse probability of treatment weighting (IPTW) was used to control for potential confounders. Results: Between 1/2010 and 12/2023, a total of 669 patients (407 CAB, 262 rDOC) with median age 72, 29% Black, 27% CD, 39% CKD, 38% DM2, were included in final analysis. For the first instance of docetaxel, patients received a median of 6 (IQR: 4-10) cycles with a PSA50 = 20%, PSA90 = 3% and a median of 1 (IQR: 0-1) additional systemic treatment prior to subsequent taxane. At the time of the initiation of the second taxane, 73% of patients had bone and 18% visceral metastases and median initial PSA of 75 ng/mL. Compared to CAB, rDOC had higher PSA90 (11% vs 3%, p<0.001), longer OS (12.5 vs 9.6 months, p<0.001) and numerically longer time to next systemic treatment (16.4 vs 12.4 months, p=0.2), shorter time on treatment (2.1 vs. 2.6 months, p=0.56), and similar PSA50 (8% vs 9%, p=0.31). The use of platinum (9% vs 6%, p=0.15), immunotherapy (2 vs 1%, p=0.79) and PARP inhibitors (6% vs 5%, p=0.67) after the second instance of a taxane was not statistically different between groups. Conclusions: In this study, rDOC was associated with better survival and deeper response than cabazitaxel. The findings of this large-scale study provide guidance for making well-informed decisions about sequential use of taxanes for mCRPC treatment.

Efficacy and safety of apalutamide in metastatic castration sensitive prostate cancer patients with a prior history of cardiovascular or metabolic risk factors: A post-hoc analysis of the TITAN study.

165 Background: Patients with CV issues, such as MI, symptomatic congestive heart failure, or thromboembolic events occurring ≤6 months of randomization were excluded from the TITAN trial. However, patients with events occurring > 6 months prior or non-excluded CV conditions like IHD without MI were enrolled. Considering the demographics of prostate cancer and given prolonged ADT use may worsen existing co-morbid conditions, we conducted a post-hoc analysis to assess the efficacy and safety of apalutamide +ADT (APA) vs placebo+ADT(PBO) in patients with ≥ 1 risk factor or a history of CV or metabolic risk factors. Methods: CV and metabolic risk factors were categorized using MeDRA terminology and included CV ischemia, CV failure, CV arrhythmia, diabetes, hyperlipidemia, HT and obesity. Use of associated concomitant medications (con meds) were identified at study entry. Data from the final analysis after 44 months of median follow up were analysed for the co-primary endpoints of rPFS and OS, along with PSA90 or PSA<0.2ng/ml and TEAEs in patients with or without CV risk factors, and with con meds for these conditions. Results: In TITAN, 72% (378/524) and 69% (364/527) patients in the APA and PBO arms had a history of CV or metabolic risk factors at baseline; 68% (358/524) and 66% (347/527) were receiving con meds for these conditions. Individual risk factors were evenly matched between arms. All efficacy endpoints rPFS, OS, PSA90 and PSA<0.2ng/ml were superior in the APA group vs PBO group irrespective of CV/metabolic Risk and with con meds . Incidence of TEAEs were similar between subjects with and without CV & metabolic risk and with concomitant medications at baseline (Table). Conclusions: A large majority of patients enrolled in TITAN reflected an elderly population with a considerable CV risk profile. APA resulted in a significant improvement in both rPFS and OS and a favourable safety profile regardless of prior CV and metabolic baseline risk or with con meds at baseline for these conditions. Clinical trial information: NCT02489318 . With CV/metabolic risk factors at baseline Without CV/metabolic risk factors at baseline With CV/metabolic risk and concomitant medications at baseline APA+ADT ADT+Placebo APA+ADT ADT+Placebo APA+ADT ADT+Placebo Subgroup prevalence n(%) 378 (72.0%) 364 (69.1%) 147 (28.0%) 163 (30.9%) 358 (68.2%) 347 (65.8%) rPFS [HR (95% CI) p-value] 0.49 (0.38, 0.63) <0.0001 0.48 (0.33, 0.7) 0.0001 0.47 (0.36, 0.62) <0.0001 OS [HR (95% CI) p-value] 0.63 (0.5, 0.8) 0.0001 0.71 (0.49, 1.02) 0.0604 0.61 (0.48, 0.78) <0.0001 PSA90 or PSA<0.2ng/ml 326 (86.2%) 157 (43.1%) 121 (82.3%) 71 (43.6%) 307 (85.8%) 146 (42.1%) TEAE (all grades) 368 (97.4%) 353 (97.0%) 142 (97.3%) 157 (96.3%) 350 (97.8%) 337 (97.1%) Gr 3/4 TEAE 183 (48.4%) 165 (45.3%) 76 (52.1%) 55 (33.7%) 177 (49.4%) 161 (46.4%)

Cardiovascular mortality risk in primary penile cancer patients: A retrospective cohort study from 2000 to 2021.

7 Background: Primary penile cancer is a rare malignancy, representing less than 1% of all cancers in men in developed countries. The disease predominantly affects older males and is frequently associated with risk factors such as human papillomavirus (HPV) infection, chronic inflammation, smoking, and poor hygiene. Given the age and comorbidities of patients diagnosed with penile cancer, cardiovascular disease (CVD) is a significant concern. Penile cancer patients often present with multiple risk factors for CVD, including advanced age, smoking, obesity, and pre-existing hypertension. Despite improvements in cancer-specific survival, non-cancer causes of death, particularly cardiovascular mortality (CVM), may disproportionately affect these patients. Understanding the cardiovascular mortality in penile cancer patients is crucial for holistic care and survivorship. Methods: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with primary penile cancer who experienced cardiovascular mortality (CVM) between 2000 and 2021. CVM was defined as mortality resulting from heart disease, hypertension (without concomitant heart disease), cerebrovascular disease, atherosclerosis, aortic aneurysm and dissection, and other diseases of the arteries, arterioles, and capillaries. Standardized mortality rates (SMR) were calculated to assess the relative risk of CVM among penile cancer patients compared to the general population. Absolute excess risk (AER) was also estimated to quantify the additional number of CVM-related deaths attributed to this patient population. Results: Out of a total cohort of 6,889 patients diagnosed with primary penile cancer, 689 experienced cardiovascular mortality. Patients with Non-cardiovascular death and patients with unknown ag, race and cancer stage were excluded. We compared the CVM of each group to the general US population. In our cohort based on race we didn't note statistically significant increase in CVD SMRs. Regarding race American Indians/Alaska Natives has (SMR 0.99, CI 0.24-3.98), Asians or Pacific Islanders (SMR 0.99 CI 0.68-1.46), Blacks (SMR 0.99 CI 0.75-1.33), Whites (SMR 1.00 CI 0.91-1.08). In terms of age, patients aged 30-50 years (n=27) had SMR of 0.99 (CI 0.68-1.44), 50-79 year (n=359) had SMR of 0.99 (CI 0.90-1.10), while 80 years and above (n=222) had SMR of 1.00 (CI 0.87-1.14). Conclusions: Our analysis evaluates the burden of CVD-related mortality in patients with primary penile carcinoma. In this cohort, no statistically significant increase in cardiovascular mortality was observed when compared to the general U.S. population, stratified by race and age. Further research is required to better understand potential associations or disparities and to identify any underlying factors that may influence cardiovascular outcomes in this population.

Network analysis of the relationship between error orientation, self-efficacy, and innovative behavior in nurses

Enfortumab vedotin-related skin toxicities in patients with urothelial carcinoma: A systematic review and meta-analysis.

761 Background: Enfortumab vedotin (EV) is an antibody-drug conjugate that binds nectin-4, a cell-adhesion molecule highly expressed in urothelial carcinoma (UC) and epidermal keratinocytes. Dermatologic events have become important EV-related toxicities in clinical trials (CT) and observational studies. We conducted a systematic review and meta-analysis on skin toxicity in UC patients treated with EV. Methods: We systematically searched Pubmed, Cochrane, and Embase for published CT and observational studies reporting EV-related skin toxicities in UC patients. We investigated treatment-related adverse events (TRAE) and severe cutaneous adverse reactions (SCAR) in UC patients of all-grade and ≥ 3. The outcomes were presented as overall incidence rates and 95% confidence intervals (95% CI). Statistical analyses were performed using R software. Results: Ten studies comprising 1,061 participants were included. Median age ranged from 66 to 76 years, and 74% (783) were male. 72% of patients had prior immune checkpoint inhibitors. The median time to onset of skin toxicity varied from two to four weeks. In a pooled analysis, the skin reaction rate for all-grade of UC was 50% (95% CI 38-61), while for grade ≥ 3 was 10% (95% CI 7-15). The incidence of SCAR was 19% (95% CI 16-23) and 8% (95% CI 3-18) for grade ≥ 3. Alopecia was seen in 37% of patients, pruritus in 22% and dry skin in 21%. All-grade rash incidence rate was 29% and the most reported was maculopapular rash 22%, followed by erythematous rash (6%). Important cutaneous reactions included bullous dermatitis in 2.91% of patients (95% CI 1-6), palmar-plantar erythrodysesthesia in 2.46% (95% CI 1-5), Stevens-Johnson syndrome in 1.46% (95% CI 0.4-5), and toxic epidermal necrolysis in 0.95% (95% CI 0.2-4) of patients. Conclusions: This is the first study to characterize EV-related dermatological toxicities. We found a high incidence of all-grade events and a moderate frequency of severe and grade ≥ 3 toxicities. This study intends to highlight the need for close monitoring and adequate treatment for skin toxicities in UC patients receiving EV.

Gut health and prostate cancer: The influence of a specific phytochemical-rich food capsule plus or minus a probiotic/prebiotic blend on symptoms and progression—A randomised, double-blind placebo-controlled trial.

311 Background: The "gut-prostate axis" is increasingly being recognised as an influencer of prostate cancer (PCa) incidence and progression via its affect on inflammation, oxidative stress and immune surveillance. Murine models have shown that improving the gut microbiome can slow cancer progression. Boosting phytochemical rich foods (PRF) has previously been shown to inhibit Prostatic Specific Antigen (PSA) progression in men with indolent PCa and are potent prebiotics, working in synergy with lactobacillus probiotics, and vitamin D. Until now, no study has evaluated this dietary combination in men with PCa. Methods: 212 men with PSA progressing PCa (average age 74.5 years) managed with surveillance were given a Phytochemical Rich Supplement (PRS), uniquely containing both standardised extracts and whole purified organic ginger, cranberry, pomegranate, turmeric, broccoli and green tea. Men were then randomised (1:1) to a placebo (P) or a Probiotic blend (PB) of 5 lactobacillus probiotics with prebiotic inulin and vitamin D, for 16 weeks. Results: For the 105 men on PRS+P, the average rate of PSA rise pre to post baseline changed from 19.6% to 6.2% - a statistically significant (SS) reduction of 13.4% (a paired t-test p<0.01). For the 107 men on PRS/PB, the rate changed from a 21.7% rise to a 20% fall - a reduction of 41.7% (p<0.0001). There was a SS greater difference in PSA dynamics comparing the PRS+BP v PRS+P groups (28.3%, p<0.0001).The International Prostate Symptom Score and the International Index of Erectile Function were SS better in the PRS+PB v PRS+P men (10.5 v 14.1; 26.6 v 23.7 respectively, both P<0.001). Both arms had good tolerance, 5% had some bloating but conversely 14% reported improved gut symptoms. There was no difference in testosterone levels. Pre and post MRI was available in 180 men to date. In 10, the disease was reported to shrink, 164 stabilised and 6 worsen with PSA progression at a higher than average rate in all these 6, suggesting no PSA masking effect. Conclusions: This new phytochemical rich food supplement significantly slowed PSA progression, improved urinary symptoms and erectile function in men with indolent PCa. In addition, this is the World's first double blind RCT to demonstrate that an intervention aiming to improve gut health using pre and probiotics further reduced PSA progression. Hopefully, these findings will encourage more microbiome related research in men with PCa. Further follow up will determine whether this slowing of PSA progression influenced men's decision to avoid the toxicities of radical interventions. MRI images, so far, are reassuring but longer follow up is also planned. This evidence based information, will help dietary choices and will be welcomed by men on surveillance, with whom this trial was designed. Clinical trial information: 81939514.

Prognostic value of preoperative fibrinogen in metastatic clear cell renal cell carcinoma patients undergoing cytoreductive nephrectomy: A propensity score-matched study.

563 Background: The measurement of serum fibrinogen (FIB) levels is often overlooked in metastatic clear cell renal cell carcinoma (mccRCC). This study aims to investigate the prognostic value of preoperative serum FIB levels in mccRCC patients undergoing cytoreductive nephrectomy (CN) followed by systemic therapy. Methods: This retrospective study analyzed 209 mccRCC patients who underwent CN from 2010 to 2022. The optimal cutoff value of preoperative serum FIB levels was determined via receiver operating characteristic (ROC) curve. Survival outcomes were evaluated by the Kaplan-Meier method and Cox proportional hazards models. The predictive ability was evaluated by ROC curve. Propensity Score Matching (PSM) was performed to equate demographic and clinical characteristics. Results: An optimal cutoff value of 4.39 g/L for the FIB levels was determined and patients were categorized into high and low FIB groups. With a median follow-up time of 61.1 months, patients in the low FIB group exhibited significantly higher median OS compared with the high FIB group (53.1 vs 27.9 months, p < 0.001). The ROC curve demonstrated that the serum FIB predicted a 36-month overall survival with an AUC of 0.652, while the AUC for the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk category was 0.558. After PSM matching, high FIB levels remained significantly associated with poorer OS (24.0 vs 50.2 months; p = 0.019). Conclusions: Serum FIB level is a significant prognostic factor for mccRCC patients undergoing CN followed by systemic therapy. This finding underscores the potential of FIB as a biomarker that could be integrated into the prognostic model for preoperative risk stratification and management strategies.

A data augmentation model integrating supervised and unsupervised learning for recommendation

Neoadjuvant treatment with disitamab vedotin plus perioperative toripalimab in patients with muscle-invasive bladder cancer (MIBC) with HER2 expression: Updated efficacy and safety results from the phase II RC48-C017 trial.

665 Background: This single-arm phase II trial was conducted to evaluate the efficacy and safety of neoadjuvent disitamab vedotin (DV, a HER2-targetted monoclonal antibody conjugated with monomethyl auristatin E) plus perioperative toripalimab (an anti-PD-1 inhibitor) in MIBC patients (pts) with HER2 expression. The preliminary results showed promising efficacy and acceptable safety with neoadjuvant treatment with DV plus toripalimab in pts with HER2-expressing MIBC (Sheng, et al. ASCO Annual meeting 2024). Methods: Key eligibility criteria included previously untreated MIBC (cT2-4aN0-1M0) with HER2 expression (immunohistochemistry [IHC] ≥1+ by local test), and eligible for curative-intent radical cystectomy and pelvic lymph node dissection (RC+PLND). Pts received DV (2 mg/kg) plus toripalimab (3 mg/kg) every 2 weeks for 6 cycles at neoadjuvant phase. After RC+PLND, pts received adjuvant toripalimab (3 mg/kg every 2 weeks) for up to 20 cycles. The primary endpoint was pathological complete response (pCR, ypT0N0) rate assessed by the investigators; secondary endpoints included pathological response rate (≤ypT1N0M0), overall survival, safety, etc. Here we present the updated efficacy and safety results and post-hoc event-free survival (EFS) analysis with data cutoff date (DCO) of September, 2024. Results: As of DCO, patient enrollment was completed with 47 pts enrolled and treated (including 10.6% pts with HER2 IHC 1+, 57.4% IHC 2+, and 31.9% IHC 3+; 83.0% pts at baseline T2-4N0M0 and 17.0% at cT2-4aN1M0 stage). RC+PLND was performed in 33 (70.2%) pts. The pCR rate was 63.6% (95% CI: 45.1%-79.6%) and the pathological response rate was 75.8% (95% CI: 57.7%-88.9%). A higher pCR rate of 84.6% was observed in patients with HER2 IHC 3+. The pCR rate was 77.8% and 62.5% in PD-L1-positive and PD-L1-negative subgroups, respectively. The one-year EFS rate was 89.5% (95% CI: 69.8%-96.7%). The safety profile was consistent with the previous ASCO presentation without new toxicity signals observed. No adverse events delayed the surgery. Survival data were immature. Conclusions: The updated data supported perioperative treatment with DV plus toripalimab had promising efficacy and acceptable safety in pts with HER2-expressing MIBC. It warrants further investigation in this patient population. Clinical trial information: NCT05297552 .

Preliminary results from LEGEND: A phase 2 study of detalimogene voraplasmid (EG-70), a novel, non-viral intravesical gene therapy for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS).

802 Background: Detalimogene voraplasmid is a novel, investigational, non-integrating, non-viral gene therapy specifically engineered for intravesical administration to elicit local activation of anti-tumor immune responses in the bladder and drive durable efficacy in patients with high-risk NMIBC, including BCG-unresponsive disease, while mitigating the risk of systemic toxicities from immune stimulation. Preclinically, detalimogene voraplasmid remodels the tumor microenvironment, activating both innate and adaptive anti-tumor immune responses. Results from the Phase 1 portion of LEGEND (NCT04752722) demonstrated a promising safety/tolerability profile and an overall CR of 73% in patients with NMIBC with CIS. The pivotal Phase 2 portion is ongoing, and the preliminary outcomes will be reported herein. Methods: Patient eligibility criteria: age ≥18 years; ECOG PS 0−2; BCG-unresponsive NMIBC with CIS ± Ta/T1 disease, ineligible for, or elected not to undergo, cystectomy; satisfactory bladder function with ability to retain study drug for ≥60 minutes. Based on the Phase 1 portion of the study, a dose concentration of 0.8 mg/mL was administered at a four-dose 50 mL instillation schedule at study weeks 1, 2, 5 and 6 of a 12-week cycle. After completing the initial 12-week cycle, patients without progressive disease remained on detalimogene voraplasmid for up to three additional 12-week cycles. Primary endpoint: Week 48 CR rate; secondary endpoint: safety and tolerability. Efficacy data on BCG-unresponsive patients with CIS (n=26; Cohort 1) and safety data on all patients dosed (N=42) are reported. Results: Twenty-six patients (20 males/6 females; median age 74 (range 47–92) years have been enrolled in Cohort 1. Treatment-related adverse events (TRAEs; any grade) were reported in 20 (47.6%) patients and were all Grade 1/2 in severity. The most common TRAEs were dysuria in 9 (21.4%) patients, bladder spasm in 8 (19.0%); pollakiuria in 5 (11.9%), and fatigue in 5 (11.9%) patients. In the efficacy-evaluable population for Cohort 1, the overall CR rate was 71% (15/21), with a CR rate of 67% (14/21) at 3 months, and 47% (8/17) at 6 months. The Kaplan-Meier estimate of the 6-month CR is 51%. Conclusions: Preliminary data from the pivotal Phase 2 portion of the LEGEND study suggest a promising safety/tolerability profile, with TRAEs that were largely consistent with instrumentation/intravesical administration. Overall, 71% of patients dosed with detalimogene voraplasmid achieved a CR, with 67% achieving a CR at 3 months and 47% achieving a CR at 6 months. Cohort 1 (BCG-refractory patients with CIS) continues to enroll, with a target accrual of 100 patients. Clinical trial information: NCT04752722 .

Clinical characterization and treatment patterns in patients with metastatic hormone-sensitive prostate cancer at three third-level centers of the Mexican Institute of Social Security: A retrospective cohort study.

91 Background: In Latin America, prostate cancer (PC) is the most common cancer among men. Despite efforts in select institutions in Mexico to register and organize data on patients (pts) with PC, epidemiological data are scarce. This study described the demographic, clinical, and treatment-related characteristics of pts with metastatic hormone-sensitive PC (mHSPC) in reference centers for the Mexican Institute of Social Security (IMSS). Methods: This retrospective, observational, cohort study examined the health records of adult (≥18 years) pts newly diagnosed with mHSPC between January 1, 2017, and June 30, 2023. The pts were treated at one of the three tertiary hospitals of the IMSS and received ≥1 follow-up consultation after the date of mHSPC diagnosis. Criteria for mHSPC diagnosis: ICD-10 code C61 or D40; inclusion of “prostate cancer,” “adenocarcinoma of the prostate,” or “malignant tumor of the prostate” in pt charts; radiologic confirmation and stage IV/metastatic disease diagnosis by an oncologist/urologist; hormone sensitivity with/without prior androgen-deprivation therapy (ADT) (having stopped ADT ≥12 months before confirmation of metastatic disease); or clinically equivalent diagnosis. Pts were stratified by the tumor, node, metastasis (TNM) staging system of PC (8 th ed). Only metastatic disease (i.e., any T or N and M1) was considered at baseline. Results: In total, 454 pts’ charts were reviewed:246 did not have metastatic disease, 42 had metastatic castration-resistant prostate cancer, and 166 (37%) had mHSPC. Of these 166 pts (median [SD] age, 69.5 [8.3] years),71% (n = 117)had Gleason score ≥8, 20% (n = 33) had confirmed nodal spread (N1), and 65% (n = 108) had confirmed metastasis (M1) at the time of diagnosis. Pts received the following treatments (n, %): gonadotropin-releasing hormone (GnRH) agonist (144, 87%), GnRH antagonist (5, 3%), orchiectomy (3, 2%), androgen receptor pathway inhibitor (32, 19%), and chemotherapy (31, 19%). In 35 pts, ADT was discontinued due to biochemical progression (20%), radiological progression (6%), radiological and biochemical progression (3%), or progression due to an unspecified cause (9%). There were 10 adverse events (AEs): 4 pts had grade 3 AEs, 5 pts had grade 4 AEs, and 1 pt had an AE of unspecified grade. Conclusions: This study identified clinical characteristics of and treatment variations in pts with mHSPC at the IMSS. Treatment patterns differed despite consensus in clinical guidelines. These results may help drive critical analyses of clinical decision-making, inform optimal data collection practices, and support the strengthening of cancer registries in Mexico.

A prediction model of soil organic carbon into river and its driving mechanism in red soil region

Phase 1/2 study of REGN4336 alone or in combination with cemiplimab or nezastomig in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

TPS295 Background: mCRPC is characterized by an immunosuppressive tumor microenvironment with few intratumoral effector T cells, leading to low response rates to immune checkpoint inhibitors; therefore, novel immunotherapy approaches are needed. Prostate-specific membrane antigen (PSMA) is highly expressed in malignant prostate cancer cells. REGN4336 is a PSMA×CD3 bispecific antibody (bsAb) that facilitates T-cell–mediated tumor killing by bridging PSMA-expressing tumor cells with CD3+T cells, providing “signal 1” for T-cell activation. Nezastomig (REGN5678 [PSMA×CD28 bsAb]) enhances T-cell activation/proliferation by engaging the costimulatory receptor CD28 on T-cells located in proximity to PSMA, providing “signal 2.” In preclinical models, REGN4336 demonstrated dose-dependent activity against PSMA-expressing tumor cells that was enhanced in combination with cemiplimab (anti–PD-1) or nezastomig. Preclinically, nezastomig + subtherapeutic doses of REGN4336 showed similar efficacy and reduced cytokines compared with higher doses of REGN4336 monotherapy, suggesting this strategy may mitigate cytokine release syndrome (CRS). In a separate clinical trial (NCT03972657), nezastomig + cemiplimab demonstrated promising clinical activity in mCRPC, but some responders had high-grade immune-mediated AEs. REGN4336 is a novel combination partner for nezastomig. Methods: This is an open-label, Phase 1/2, first-in-human, multicenter study evaluating REGN4336 ± cemiplimab or nezastomig in pts with mCRPC (NCT05125016). Pts must have received ≥2 lines of systemic therapy for metastatic/castration-resistant disease, including a second-generation anti-androgen. Prior PSMA-targeted radioligands are permitted. Module 1 evaluates REGN4336 monotherapy with step-up dosing to mitigate CRS; Module 2 will evaluate REGN4336 + cemiplimab; Module 3 evaluates REGN4336 + nezastomig. In Modules 2 and 3, pts will receive REGN4336 step-up dosing until tolerated with Grade ≤1 CRS, followed by combination therapy. Module 1 began with REGN4336 administered SC; in addition, Modules 1–3 may evaluate REGN4336 administered IV (+ sarilumab [anti–IL-6] for CRS prophylaxis) to compare tolerability, PK, and immunogenicity across routes. Treatment continues until disease progression, intolerable AEs, or other withdrawal criteria are met. Dose escalation primary objectives: assess safety, tolerability, and PK, and determine RP2D regimens of REGN4336 ± cemiplimab or nezastomig. Dose expansion primary objectives: evaluate antitumor activity of REGN4336 ± cemiplimab or nezastomig (ORR per modified PCWG3 criteria). Exploratory objectives include PSMA-PET imaging and tissue-based biomarker analysis. This is the first study to evaluate combined ×CD3 + ×CD28 bsAb in mCRPC. As of Sept 12, 2024, 35 pts have been enrolled, including 4 in Module 3. Clinical trial information: NCT05125016 .

Patient-reported outcome (PRO) assessment and reporting in first-line (1L) locally advanced or metastatic urothelial cancer (la/mUC) clinical trials: Results of a systematic literature review (SLR).

757 Background: Although maintaining health-related quality of life (HRQOL) is a primary goal of advanced cancer care, HRQOL and PROs usually are not measured or reported as robustly as efficacy outcomes in clinical trials. One example is la/mUC, an aggressive and incurable disease with a profound effect on patient HRQOL and functioning. With its changing therapeutic landscape in which newer agents with various efficacy and toxicity profiles are incorporated into clinical care, more attention must be given to the optimal deployment of PRO measures (PROMs). Our aim was to conduct a critical evaluation of currently used PROMs in la/mUC 1L trials. Methods: A SLR was conducted using 5 online databases to identify publications up to May 29, 2024 and recent conference abstracts of phase 2 or 3 clinical trials and real-world evidence (RWE) studies reporting PROs in the treatment of la/mUC. Results: Forty-nine studies were identified in the SLR (37 clinical trials; 12 RWE studies). Of the 37 clinical trials, 18 were in the 1L population. The most common PROMs in 1L trials were the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (n = 15) and the EuroQol-5D (n = 6). Other PROMs used were the Brief Pain Inventory–Short Form (n = 2), Functional Assessment of Cancer Therapy–Bladder (FACT-Bl; n = 1), National Comprehensive Cancer Network/FACT Bladder Symptom Index-18 (n = 1), and the Generic Quality of Life Inventory-74 (n = 1). PROMs were almost exclusively included as secondary endpoints (n = 16); only 2 trials included PROMs as exploratory endpoints. Prespecified analyses for HRQOL assessments were generally not stated in publications, and analytical methods and reporting varied. Of the 15 trials that used the EORTC QLQ-C30, 93% reported general health status/QOL, and 60% and 47% reported functional and symptom scales, respectively. Overall, HRQOL, functioning, and/or symptoms were maintained or improved, but meaningful changes in PRO scores reported were difficult to interpret due to the ways in which minimal clinically important difference thresholds were applied. Conclusions: Understanding the impact of various 1L treatment regimens on PROs relies on consistent assessment and transparent reporting. The findings of this SLR highlight the challenges in conducting cross-trial comparisons of PROs due to heterogeneity in study designs, patient characteristics, choice of PROMs, statistical analyses, and reporting of outcomes. To understand the symptom burden associated with novel therapeutics, it is recommended that the la/mUC research community develop a consensus regarding PRO development and implementation. This will facilitate interpretation of the patient experience, enhance clinical care, and guide informed treatment decision-making by clinicians and patients with la/mUC.

Outcomes with tandem or triplet autologous stem cell transplant for refractory germ cell tumors.

632 Background: While Germ Cell Tumor (GCT) remain highly curable, up to 40% of patients (pts) with intermediate or poor risk advanced GCT will relapse. In the relapsed setting, high dose chemotherapy followed by autologous hematopoietic cell transplant (AHCT) may be pursued with curative intent. To predict the risk of post-AHCT relapse, the International Prognostic Factors Study Group created 5 risk categories incorporating 7 variables. The IPFSG score was created prior to the popularization of tandem/triplet transplants and validated in patients coming to AHCT in first relapse. Methods: We performed a retrospective analysis of all pts with GCT treated with AHCT at Stanford from 2017-2024. Pts were included if they were planned for doublet "tandem" (N Engl J Med 2007;357:340) or triplet (J Clin Oncol 2010;28:1706) AHCT with at least two months of follow up. Baseline characteristics, treatment history and outcomes were analyzed. For pts who came to transplant after >1 relapse, their IPFSG score was calculated based on most recent therapy prior to AHCT. Median relapse free survival (mRFS), overall survival (mOS), and 1-year outcomes were calculated from the final transplant and stratified by IPFSG score. A cox proportional analysis was performed to evaluate the multivariate for age, site of primary tumor, presence of brain metastases, and number of relapses prior to AHCT. Results: 57 pts were included in the analysis. Median age was 29 years (range 18-52). All pts were mobilized with G-CSF and underwent conditioning with carboplatin and etoposide. Three (5%) pts were planned for tandem and 54 (95%) for triplet AHCT. Most (97%) were non-seminomas or mixed germ cell tumors. 12 (21%) pts were transplanted after >1 relapse. The disease status at time of AHCT was partial remission tumor marker (PRM) negative in 9 (16 %), PRM positive in 43 (75%) and progressive disease in 5 (9%). 13 (23%) pts did not complete all scheduled transplants, all due to progression of disease. The median follow-up for the entire cohort was 330 days. The mRFS was 115 days, and mOS was 344 days. For the 49 pts at least one year from transplant, one-year RFS and OS are shown in the table. In a multivariate analysis, there was no association between death and age, site of primary tumor, presence of brain metastasis, disease status at transplant, or number of recurrences. Conclusions: Long term outcomes for patients with refractory GCT remain poor, though a subset of patients may still be cured with AHCT. The IPFSG accurately prognosticates outcomes in our real-world analysis. Outside of their contribution to IPFSG, variables such as disease status at transplant, site of metastasis, and number of recurrences did not have statistical significance. 1 year RFS and OS by IPFSG score. IPFSG Score Very low Low Intermediate High Very High Overall 1 yr RFS 100% (3/3) 66% (2/3) 78% (7/9) 20% (5/25) 11% (1/9) 37% (18/49) 1 yr OS 100 (3/3) 100% (3/3) 89% (8/9) 44% (11/25) 33% (3/9) 57% (28/49)