5071 Background: Olaparib, a targeted therapy for metastatic castration-resistant prostate cancer (mCRPC), has demonstrated clinical benefits in patients with homologous recombination repair (HRR) gene alterations, as shown in the PROfound trial. As the largest integrated healthcare system in the US, the Veteran’s Health Administration (VHA) offers insights into olaparib use among a diverse population. We characterized the treatment patterns and outcomes of patients with mCRPC treated with olaparib. Methods: We identified all VHA patients with mCRPC who received olaparib between May 2020 and December 2023. We then performed a retrospective chart review of data from May 2018 to June 2025 to capture pre- and post-treatment data. Demographics, baseline characteristics, biomarker testing and treatment sequencing were summarized. We analyzed time to event outcomes: time to next therapy (TTNT), and overall survival (OS) via Kaplan-Meier methods, both starting from olaparib initiation. Results: We identified 477 mCRPC patients receiving olaparib. Median age at initiation was 75, older than subjects in PROfound (median age 69). Most patients were non-Hispanic White (69%), followed by Black/African American (20%) and Hispanic/Latino (6%). Between 2020 and 2023, olaparib was most commonly initiated in ≥5th line after prostate cancer diagnosis (46%), followed by 4 th (25%), 3 rd (22%), and 2 nd line (6.5%). All patients had received an androgen receptor pathway inhibitor prior to olaparib. Median time from HRR testing to olaparib initiation was 5 months. Median TTNT was 7 months; OS was 12 months. Use of olaparib in an earlier line post first NHA was associated with numerically longer OS (17 months for 1st line vs. 8 months for 4th or later). Conclusions: Within the VHA, olaparib showed favorable outcomes despite older age and late-line use, supporting effectiveness in routine practice and in a more diverse population with substantially higher representation of Black/African American and Hispanic/Latino individuals than in clinical trials. Understanding these treatment patterns provides insight into clinical practice and helps guide towards optimal integration of olaparib into management of mCRPC. Kaplan-Meier estimates for time to event outcomes. #Events/Total Median Time (95% CI) (months) Time to Next Treatment - All Patients 449/477 7 (6-8) - Olaparib Line of Treatment Post NHA 1st line 100/111 9 (7-10) 2nd line 151/162 8 (7-10) 3rd line 92/96 6 (5-8) 4th line or later 91/92 5 (4-6) Overall Survival - All Patients 395/477 12 (11-13) - Olaparib Line of Treatment Post NHA 1st line 79/111 17 (12-22) 2nd line 133/162 15 (12-17) 3rd line 85/96 10 (8-12) 4th line or later 88/92 8 (6-9)

Importance:In the US, Black patients with cancer consistently experience worse survival compared to White patients, even after adjusting for age, sex, and disease stage. Whether these disparities exist among patients receiving care in the Veterans Health Administration (VHA), an integrated health system designed to provide near-equal access to care, remains uncertain. Objective:To evaluate whether overall survival (OS) and cancer-specific survival (CSS) differ between Black veterans and those with other race receiving cancer care through VHA. Data Sources:PubMed was searched from January 2015 through April 2022. Reference lists from identified studies were also reviewed. Study Selection:Studies of US veterans receiving cancer care through the VHA were included if they reported OS or CSS by race and provided hazard ratios (HRs). Dual independent rating of titles and abstracts was conducted for inclusion. Data Extraction and Synthesis:A random-effects model was used to pool effect sizes, the Paule-Mandel estimator was used to calculate the heterogeneity variance τ2, and Knapp-Hartung adjustments were used to calculate the confidence interval of the pooled effect. Review and meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. Main Outcomes and Measures:OS and CSS were compared between Black veterans and those who were not Black using pooled HRs. Results:Of 101 studies identified, 39 met inclusion criteria and 29 provided sufficient data for meta-analysis. The reported outcomes represented 603 256 veterans with cancer treated between 1983 and 2017, with a mean 29.0% (range, 8.9%-55.0%) of patients categorized as Black. All studies compared race by Black compared with White, except for 7 of 20 prostate cancer studies, which compared race by Black compared with non-Black. Black veterans were found to have better OS (HR, 0.93; 95% CI, 0.89-0.97) and CSS (HR, 0.94; 95% CI, 0.90-0.98). Survival advantages for Black veterans were observed across several cancer types, including bladder, laryngeal, lung, oropharyngeal, prostate, and plasma cell cancers. Between-study heterogeneity was low to moderate. Conclusions and Relevance:In this systematic review and meta-analysis of peer-reviewed publications reporting the outcomes of veterans receiving cancer care through VHA, survival outcomes were generally similar or better for Black compared with White or non-Black veterans. These findings suggest that integrated health care systems providing near-equitable access to comprehensive cancer care can substantially reduce or eliminate disparities in cancer outcomes.

Purpose A recently published phase 2 neoadjuvant trial in patients with early-stage non-small cell lung cancer (NSCLC) (NCT02818920) evaluated the potential efficacy of pembrolizumab administration in the absence of chemotherapy. This communication reports on conventional and distribution-based immune profiling efforts in efforts to identify novel biomarkers predictive of benefit.Methods Patients with stage 1B-3A NSCLC received two cycles of pembrolizumab (P), followed by surgical resection of the remaining tumors (NCT02818920). Banked peripheral blood mononuclear cells (PBMCs) were analyzed at baseline and following the second dose of P. Resected tumors were disaggregated, and cells were viably cryopreserved. Based on pathologic examination of the tumors, patients were categorized as major pathologic responders (MPR; ≤10% viable tumor present), or non-MPR (>10% viable tumor present). High-parameter immune phenotyping by flow cytometry was performed on all available tumor and PBMC specimens, and results were expressed using both conventional phenotypic frequency analyses as well as a novel distribution-based biomarker identification strategy aimed at discovery of patterns associated with MPR.Results Conventional, frequency-based flow cytometric immune phenotyping of participant tumor microenvironments and PBMC revealed several MPR-associated trends, only a few of which reached statistical significance. The distribution-based biomarker identification strategy greatly enhanced the discovery of statistically significant cell types and patterns of change associated with MPR.Conclusions This novel, distribution-based analytic framework identified MPR-associated immune cell subsets in baseline PBMC that were not evident using conventional frequency-based immune profiling. Profiling the microenvironment of MPR-associated tumors revealed statistically significant distributional differences among highly expressed cellular markers on CD8+ cells.

AbstractGT103 is a first-in-class, fully human, IgG3 monoclonal antibody targeting complement factor H that kills tumor cells and promotes anti-cancer immunity in preclinical models. We conducted a first-in-human phase 1b study dose escalation trial of GT103 in refractory non-small cell lung cancer to assess the safety of GT103 (NCT04314089). Dose escalation was performed using a “3 + 3” schema with primary objectives of determining safety, tolerability, PK profile and maximum tolerated dose (MTD) of GT103. Secondary objectives included describing objective response rate, progression-free survival and overall survival. Dose escalation cohorts included GT103 given intravenously at 0.3, 1, 3, 10, and 15 mg/kg every 3 weeks, and 10 mg/kg every 2 weeks. Thirty one patients were enrolled across 3 institutions. Two dose-limiting adverse events were reported: grade 3 acute kidney injury (0.3 mg/kg) and grade 2 colitis (1 mg/kg). No dose-limiting toxicities were noted at the highest dose levels and the MTD was not reached. No objective responses were seen. Stable disease occurred in 9 patients (29%) and the median overall survival was 25.7 weeks (95% confidence interval [CI], 19.1–30.6). Pharmacokinetic analysis confirmed an estimated half life of 6.5 days. The recommended phase 2 dose of GT103 was 10 mg/kg every 3 weeks, however further dose optimization is needed given the absence of an MTD. The study achieved its primary objective of demonstrating safety and tolerability of GT103 in refractory NSCLC.

Limited real-world data exist on the effectiveness of treatment intensification (TI) with androgen receptor pathway inhibitors (ARPI) in de novo metastatic castration-sensitive prostate cancer (mCSPC). This study compared outcomes of TI or first-generation nonsteroidal antiandrogens (NSAAs) to androgen-deprivation therapy (ADT) alone in US patients with de novo mCSPC. Veterans Affairs patients with de novo mCSPC (February 2018–June 2020) confirmed via chart review were grouped into ADT alone, ADT + NSAAs, or ADT + ARPI cohorts using predefined recruitment quotas. Outcomes included inverse probability of treatment weighting (IPTW)-adjusted overall survival (OS), progression to metastatic castration-resistant prostate cancer (mCRPC), and prostate-specific antigen (PSA) response. A total of 384 patients were identified (ADT alone: 163, ADT + NSAA: 101, ADT + ARPI: 120). Median follow-up was 37.2, 38.1, and 34.8 months for ADT alone, ADT + NSAA, and ADT + ARPI, respectively. Compared with ADT alone, ADT + ARPI showed significantly better OS (HR [95% CI]: 0.61 [0.43 to 0.87], p = 0.007), lower risk of progression to mCRPC (0.46 [0.33 to 0.66], p < 0.001), and higher PSA response rate (PSA decline of ≥50% and ≥90% from baseline, and to <0.2 ng/mL and <0.1 ng/mL any time during first-line treatment; all p < 0.05). Outcomes with ADT + NSAA did not differ from ADT alone. ADT + ARPI was the most common second-line mCSPC and first-line mCRPC treatment. First-line ADT + ARPI was associated with significantly improved outcomes vs ADT alone in de novo mCSPC. These real-world results align with the benefits demonstrated in trials, supporting integration of TI with ARPIs into clinical practice to improve survival outcomes in patients with de novo mCSPC.

Background Our study was designed to determine the safety, efficacy, and immunological effects of perioperative pembrolizumab in early-stage NSCLC.Methods This is a single-arm phase II study of perioperative pembrolizumab in patients with untreated, clinical stage IB to IIIA NSCLC. Patients received two doses of 200 mg pembrolizumab, surgery, standard adjuvant chemotherapy, followed by four doses adjuvant pembrolizumab. The primary objective of this study was to determine surgical feasibility rate, and secondary objectives are pathological response rate, treatment adverse events, efficacy data, and exploratory analysis of biomarkers.Results 30 patients initiated perioperative pembrolizumab, and 25 completed tumor resection. At median follow-up of 59 months after surgical resection, seven patients had disease progression, while six had died representing. A 5-year progression-free survival (PFS) from time of surgery was 72.0% (56.4%–91.9%) and overall survival (OS) from time of surgery was 75.8% (60.7%–94.7%). Major pathological response (MPR) was found in seven tumors (28%) including two complete responses (4%). Across all treated patients, four receiving neoadjuvant and four receiving adjuvant pembrolizumab experienced treatment-related adverse events of grade 3 or higher with no grade 5 events. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased across our patient cohort over time from baseline until postsurgery and remained elevated at the end of treatment. There was a significant difference between mean plasma PCSK9 levels for patients with MPR versus all other patients on study when checked postoperatively.Conclusions Perioperative pembrolizumab was safe and effective with promising MPR rate, PFS, and OS.

BACKGROUND:Treatment options for patients with advanced non-small cell lung cancer (NSCLC) with disease progression following immune checkpoint inhibitor (ICI) and platinum-based chemotherapy are limited. GT103 is a fully human immunoglobulin G3 monoclonal antibody targeting complement factor H, which promotes antitumor immunity. In a Phase I study, GT103 was well tolerated and maximum tolerated dose was not reached. METHODS:A single arm, Simon two-stage, Phase II study was conducted that evaluated efficacy and safety of GT103 plus pembrolizumab in patients with advanced NSCLC who have had progression on up to two lines of therapy, including an ICI. Patients with actionable genomic drivers were eligible if they had received at least one targeted therapy. Patients received GT103 10 mg/kg and pembrolizumab 200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity. Primary objectives were safety and objective response rate. Secondary objectives were overall survival and progression-free survival. RESULTS:Twenty-one patients were enrolled. Most common treatment-related adverse events occurring in ≥10% of patients were fatigue (24%, n = 5) and decreased lymphocyte count (24%, n = 5). One patient experienced grade 3 treatment-related adverse events, including pneumonitis and decreased lymphocyte count. Objective response rate was 10% (95% CI, 1-30) with two objective responses (1 complete response (CR), 1 partial response (PR)). Disease control rate (= CR + PR + stable disease (SD)) was 67% (n = 14). Four patients (19%) experienced disease control for over 9 months. Median progression-free survival was 2.6 months (95% CI, 1.4-4.0) and median overall survival was 10.3 months (95% CI, 6.6-NE). CONCLUSION:Combination of GT103 with pembrolizumab was well tolerated with no new safety signals. A subset of patients experienced durable responses and disease control despite prior exposure to ICI.

BACKGROUND:There are no population-level studies assessing 18F-fluciclovine (fluciclovine) utilization of Positron emission tomography/computed tomography (PET/CT) for biochemically recurrent prostate cancer (PC). We assessed fluciclovine PET/CT in the Veterans Affairs Health Care System. METHODS:Of 1153 men with claims suggesting receipt of fluciclovine PET/CT, we randomly reviewed charts of 300 who indeed underwent fluciclovine PET/CT. The primary outcome was fluciclovine PET/CT result (positive or negative). Comparison among groups stratified by androgen deprivation therapy (ADT) (yes vs. no) and prostate-specific antigen (PSA) (≤1 vs. >1 ng/mL) at imaging were performed. Logistic regression tested associations between PSA, ADT receipt, and race with fluciclovine PET/CT positive imaging. RESULTS:Fluciclovine PET/CT positivity rate was 33% for patients with PSA 0-0.5 ng/mL, 21% for >0.5-1.0, 54% for >1.0-2.0, and 66% for >2.0 (p < 0.01). A 59% positivity rate ocurred in patients treated with concurrent ADT versus 37% in those not on ADT (p < 0.01). White were more likely to have a positive scan versus Black patients (55% vs. 38%; p = 0.02). Patients whose primary treatment was radical prostatectomy had a lower positivity rate (33%) versus those treated with radiotherapy (55%) (p < 0.001). On multivariable logistic regression, PSA > 1 ng/mL (all men odds ratio [OR]: 4.06, 95% confidence interval [CI]: 2.07-7.96; men on ADT only OR: 4.42, 95% CI: 1.73-11.26) and use of ADT (OR: 3.94, 95% CI: 1.32-11.75), and White (all men OR: 2.22, 95% CI: 1.20-4.17) predicted positive fluciclovine PET/CT. CONCLUSION:This real-world study assessing 18F-fluciclovine PET/CT performance in an equal access health care system confirms higher detection rates than traditional imaging methods, but positivity is highly influenced by PSA at time of imaging. Additionally, patients currently receiving ADT have at least four times higher likelihood of a positive scan, showing that scan positivity isn't negatively affected by ADT status in this study. Finally, White men were more likely to have a positive scan, the reasons for which should be explored in future studies.

145 Background: With multiple phase 3 trials showing improved overall survival (OS) with doublet therapy (androgen-deprivation therapy [ADT]+ARPI), it has become the standard of care for pts with mCSPC. However, data on RW effectiveness of ARPI doublets are limited. This study assessed OS, time to progression to metastatic castration-resistant prostate cancer (mCRPC), and PSA decline to <0.2 ng/mL in pts with de novo mCSPC on ADT alone vs ADT+ARPI doublets or ADT+first-generation nonsteroidal antiandrogens (NSAAs). Methods: Men in the Veteran’s Health Administration with ≥1 ICD code for PC and de novo mCSPC diagnosis confirmed by clinical chart review were identified and categorized into first-line (1L) ADT alone, ADT+NSAA, or ADT+ARPI cohorts (study period: Feb 2018−Mar 2023). Target recruitment quotas ensured representation of each treatment (Tx) regimen. Index date was the ADT initiation date. OS and time to mCRPC were calculated using inverse probability of Tx weighting (IPTW)-adjusted Cox regression. IPTW-adjusted incidence rate ratios (IRR) of the proportion of pts with PSA decline to <0.2 ng/mL at any time during 1L Tx were estimated using Poisson regression. Results: 384 men with de novo mCSPC were identified (Table). Median follow-up range was 34.8–38.1 mo. 1L Tx duration for ADT+ARPI was over twice as long as ADT alone (Table). Importantly, pts on ADT+ARPI had a 39% lower risk of death vs ADT alone (HR: 0.61, 95% CI: 0.43–0.87); while OS was similar between ADT+NSAA vs. ADT alone (HR: 1.09, 95% CI: 0.79–1.49). Consistent with the improved OS, ADT+ARPI showed a 54% lower risk of progression to mCRPC (HR: 0.46, 95% CI: 0.33–0.66) and significant superiority in achieving PSA <0.2 ng/mL (57% vs 17%; Table) than ADT alone. Conclusions: This is one of the first RW studies to validate clinical trial findings of the effectiveness of ARPI-doublets for de novo mCSPC as evidenced by significantly improved OS, time to mCRPC, and PSA response. ADT+NSAA may have limited value vs ADT alone, and ARPI-doublet is an effective Tx for de novo mCSPC. [Table: see text]

e14588 Background: CFH is a complement regulatory protein that protects cells from alternative complement pathway activation. Neutralizing antibodies against CFH on tumor cells increase deposition of C3b, facilitate antibody-dependent-cellular phagocytosis and complement dependent cytotoxicity, inhibit tumor growth, and modulate anti-tumor immunity. GT103 is a first-in class, fully human-derived IgG3 anti-CFH monoclonal antibody that recognizes a tumor specific epitope on CFH and has shown anti-tumor activity in preclinical models. Methods: We conducted a phase Ib, first-in-human, dose escalation trial evaluating safety and preliminary efficacy of GT103 in patients (pts) with advanced NSCLC refractory to standard therapies. Pts received GT103 intravenously across six dose levels/schedules following 3+3 design. Primary objectives were to determine maximum tolerated dose (MTD), recommended phase II dose (RP2D), and pharmacokinetic profile of GT103. Secondary objectives were to assess objective response rate, progression free survival (PFS), and overall survival (OS). Here we present updated safety and efficacy results of the study. Results: 31 pts were enrolled from 6/2020 to 9/2023 (median age 63yrs (range, 23-79), 61% had adenocarcinoma, 32% had previously treated brain metastasis). MTD was not reached. Treatment related AEs (TRAEs) observed in ≥10% pts included fatigue (19%), anemia (16%), diarrhea (16%), and nausea (13%). 3 pts developed ≥ grade 3 TRAE, including acute kidney injury, decreased lymphocyte count, and anemia. The best treatment response was stable disease in 9 (29%) pts. Median(m) PFS and mOS were 6 weeks (95% CI 6.0-6.1) and 25.7 weeks (95% CI 19.1-30.6), respectively. 24-week PFS and OS were 9.7% (95% CI 2.5-22.9%) and 50.6% (95% CI 31.9-66.6%), respectively. PD-L1 expression was available in 25 pts. No statistically significant difference (p=0.33) was noted in mPFS between PD-L1 positive (TPS > 1%) vs negative (TPS ≤1%) pts. KRAS and EGFR mutation status was available for 22pts. mPFS and mOS were numerically longer in pts with KRAS positive vs negative disease. While there was no difference in mPFS, 24-weeks PFS was 0 vs 16.7% (95% CI 4.1-36.5%) EGFR MUT vs wild type disease. Biomarker analysis of complement regulatory proteins, FcGR expression and polymorphisms, and changes in sC5b-9 is underway. Conclusions: GT103 was well tolerated across all dose levels. The RP2D of 10mg/kg IV every 3 weeks was selected, although PK modeling will be performed to optimize the dosing schedule. Encouraging anti-tumor activity was seen in heavily pretreated pts with advanced NSCLC with a subset of patients experiencing stable disease lasting for longer than 6 months. Additional biomarker analysis is ongoing. A phase II trial combining GT103 with pembrolizumab in pts with advanced NSCLC is currently enrolling. Clinical trial information: NCT04314089 .

9128 Background: GT103 is a first-in-class IgG3 monoclonal antibody that was derived from a single human B cell and inhibits complement factor H (CFH). CFH is implicated in cancer immune evasion and overexpression portends a poor prognosis in multiple malignancies. CFH regulates C3 convertase in the alternative pathway of the complement cascade, limiting downstream opsonization and membrane attack complex formation. Monoclonal antibody inhibition of CFH facilitates complement-dependent tumor cell lysis, modulates the adaptive immune response, and inhibits tumor growth. Methods: GT103 is being evaluated in a multi-institutional, first-in-human, phase Ib study in patients with advanced stage, refractory NSCLC. A standard ‘3+3’ dose escalation schema was used across four dose levels, with treatment given until disease progression or unacceptable toxicity. Dose limiting toxicity (DLT) observation period included cycle 1 and radiographic disease assessment was performed every 6 weeks. We have previously reported that no DLT was seen at the highest two dose levels of 3 mg /kg or 10 mg/kg administered IV every 3 weeks. Two expansion cohorts have now been opened at 10 mg/kg IV every 2 week and 15 mg/kg every 3 weeks dose levels allowing up to 6 patients at each dose level. We herein present updated clinical outcomes and analysis of correlative biomarkers. Results: As of February 3, 2023, twenty-five patients have been treated, with a median follow up of 230 days. Five of the 21 patients in the dose escalation cohort demonstrated stable disease by RECIST criteria. In the 10 mg/kg dose level, one patient has experienced prolonged disease stabilization and has received 12 cycles to date with tumor reduction on CT. The DLT period is ongoing for two patients enrolled in the 10 mg/kg IV every 2 weeks and two patients in the 15 mg/kg every 3 weeks expansion cohorts. Soluble C5b-9 (s C5b-9) is a candidate pharmacodynamic biomarker for GT103 and was measured at baseline and at day 15 from patients in all four dose escalation levels (0.3, 1, 3, 10 mg/kg). An increase in sC5b-9 was found in 13 of 21 patients at day 15. A marked doubling of the baseline sC5b-9 level was demonstrated in a subset of patients by day 15 indicative of biologic activity. Conclusions: GT103 is well tolerated in heavily pretreated advanced NSCLC population. Early clinical activity has been demonstrated to date with stable disease seen in 24% of patients. Updated clinical results and correlative data will be presented. A separate phase 2 study of combination GT103 with pembrolizumab is planned for patients with refractory NSCLC. Trial Registration: The study was approved by Duke University IRB with approval number Pro00104564. Clinical trial information: NCT04314089 .

2569 Background: MEM-288 is a conditionally-replicative oncolytic adenovirus expressing human IFNβ and a recombinant membrane-stable form of CD40L (MEM40). Preclinical studies show MEM-288 induces robust dendritic cell-mediated systemic T cell responses capable of inhibiting abscopal tumor growth as monotherapy and synergizes with immune checkpoint inhibitors (ICI). Methods: MEM-288 is being evaluated in this Phase 1 open-label trial (NCT05076760) in pts with select solid tumors including NSCLC (a) refractory to standard therapy and (b) with a tumor lesion deemed feasible for biopsy and MEM-288 intratumoral (i.t.) injection. The primary objective is to determine using a BOIN design a recommended phase II dose of MEM-288 across 3 dose levels (DL1-3) spanning 1e10 to 1e11 viral particles by i.t. injection once every 3 weeks. Secondary objectives include efficacy assessment, including response rate of injected and non-injected tumors assessed separately. Tumor biopsies obtained immediately prior to the 1st and 2nd injections are used to explore biomarkers and anti-tumor immune responses. Results: As of February 2023, 12 pts (11 NSCLC and 1 pancreatic cancer; n = 3 DL1, n = 5 DL2, n = 4 DL3) have enrolled. The median number of MEM-288 i.t. injections was 2 (1-3), median age was 63 (39-76), and median prior lines of therapy was 3 (1-5). Radiology-guided injections were administered in superficial/palpable tumors and visceral lesions. No dose limiting toxicities occurred. Treatment-related adverse events observed in > 1 pt include grade 1 injection site reaction (42%) and chills (17%). Of 10 response-evaluable pts, 4 (40%) pts had shrinkage of injected tumor (range -26 to -54%): 3 (30%) PR and 1 (10%) SD. Multiple pts also had stabilization or shrinkage of distal non-injected lesions. Best overall response was 3 (30%) stable disease and 7 (70%) progressive disease. After a single MEM-288 injection, biopsies show decreased tumor cell percentage concomitant with substantial increases in overall CD8 + T cells, increased T clonotype diversity in both tumor and peripheral blood, and increased TCF1 + stem-like CD8 + T cells that are strongly associated with response to ICIs. Plasma cytokine analysis showed increases in IFNg and of IFN-inducible cytokines and chemokines, supportive of stimulation of systemic response after MEM-288. Of note, a pt with strong stimulation of tumor and systemic T cell immunity after MEM-288 had subsequent CR (ongoing > 7 months) to docetaxel + ramucirumab following prior treatment failure with platinum doublet + ICI received before MEM-288. Conclusions: Preliminary safety, antitumor and immune response data are encouraging. Updated results and immune data from this study will be presented. An expansion arm is planned with combination MEM-288 and anti-PD1 antibody in pts with advanced NSCLC refractory to ICI. Clinical trial information: NCT05076760 .

Obesity and smoking have been associated with poor prostate cancer (PC) outcomes. We investigated associations between obesity and biochemical recurrence (BCR), metastasis, castrate resistant-PC (CRPC), PC-specific mortality (PCSM), and all-cause mortality (ACM) and examined if smoking modified these associations. We analyzed SEARCH Cohort data from men undergoing RP between 1990 and 2020. Cox regression models were used to estimate hazard ratios (HRs) and 95

Background: For patients with stage IV non-small-cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions and exon 21 L858R mutations, osimertinib is the standard of care. Investigating the activity and safety of osimertinib in patients with EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations is of clinical interest. Patients and methods: Patients with stage IV non-small-cell lung cancer with confirmed EGFR exon 18 G719X, exon 20 S768I, or exon 21 L861Q mutations were eligible. Patients were required to have measurable disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. Patients were required to be EGFR tyrosine kinase inhibitor-naive. The primary objective was objective response rate, and secondary objectives were progression-free survival, safety, and overall survival. The study used a two-stage design with a plan to enroll 17 patients in the first stage, and the study was terminated after the first stage due to slow accrual. Results: Between May 2018 and March 2020, 17 patients were enrolled and received study therapy. The median age of patients was 70 years (interquartile range 62-76), the majority were female (n = 11), had a performance status of 1 (n = 10), and five patients had brain metastases at baseline. The objective response rate was 47% [95% confidence interval (CI) 23% to 72%], and the radiographic responses observed were partial response (n = 8), stable disease (n = 8), and progressive disease (n = 1). The median progression-free survival was 10.5 months (95% CI 5.0-15.2 months), and the median OS was 13.8 months (95% CI 7.3-29.2 months). The median duration on treatment was 6.1 months (range 3.6-11.9 months), and the most common adverse events (regardless of attribution) were diarrhea, fatigue, anorexia, weight loss, and dyspnea. Conclusions: This trial suggests osimertinib has activity in patients with these uncommon EGFR mutations.

461 Background: Prior studies suggest that white light cystoscopy (WLC) alone can fail to detect cases of non-muscle invasive bladder cancer (NMIBC) compared to blue light cystoscopy (BLC). We describe bladder cancer outcomes and the impact of BLC among NMIBC patients in an equal access setting. Methods: A total of 378 NMIBC patients within the Veterans Affairs system that had a CPT code for BLC from December 1, 2014 to December 31, 2020 were assessed. We determined recurrence rates and time to recurrence prior to BLC (i.e. after previous WLC if available) and following BLC. We used the Kaplan-Meier method to estimate event-free survival and Cox regression to determine the association between race and recurrence, progression, and overall survival. Results: Of 378 patients with complete data, 43 (11%) were Black and 300 (79%) White. Median follow-up was 40.7 months from bladder cancer diagnosis. There were 194 (51%) patients with either TaHG or T1 without CIS; 52 (14%) had CIS with or without TaHG or T1; and 127 (34%) had TaLG only. A total of 239 (63%) patients received BCG at any point during the study. Median time to first recurrence following BLC was longer compared to WLC alone (40 (33-NE) vs. 26 (17-39) months). The risk of recurrence was significantly lower following BLC (Hazard Ratio (HR) 0.70; 95% Confidence Interval (CI) 0.54-0.90). There was no significant difference in recurrence (Hazard Ratio (HR) 0.83; 95% Confidence Interval (CI) 0.48-1.43), progression (HR 1.46; 95% CI 0.45-4.74), and overall survival (HR 0.69; 95% CI 0.29-1.65) following BLC by Black vs. White race. Conclusions: In this study from an equal access setting in the VA, we observed significantly decreased risk of recurrence and prolonged time interval to recurrence following BLC compared to WLC alone. There was no difference in any bladder cancer outcomes by race.

Background: MEM-288 is a conditionally-replicative oncolytic adenovirus expressing human IFNβ and a recombinant membrane-stable form of CD40L (MEM40). Preclinical studies show MEM-288 induces robust dendritic cell-mediated systemic T cell responses capable of inhibiting abscopal tumor growth as monotherapy and synergizes with immune checkpoint inhibitors (ICI). Methods: Safety, antitumor and immunologic activity of MEM-288 are being evaluated in this Phase 1, multicenter, open-label trial (NCT05076760). Pts with select solid tumors including NSCLC (a) refractory to standard therapy and (b) with a tumor lesion deemed feasible for biopsy and MEM-288 intratumoral injection are eligible. The primary objective is to determine a recommended phase 2 dose of MEM-288 monotherapy across 3 dose levels (DL1-3) spanning 1e10 to 1e11 viral particles by intratumoral injection once every 3 weeks, for up to 6 injections, using a BOIN design. Secondary objectives include efficacy assessment (including response rate of injected and non-injected tumors assessed separately). Tumor biopsies immediately prior to the 1st and 2nd injections, and peripheral blood at serial timepoints, are used to explore biomarkers and anti-tumor immune responses. Results: As of Jan 2023, the study is ongoing with the DL3 high-dose cohort completing accrual. 11 pts (10 NSCLC and 1 pancreatic) enrolled and received ≥1 dose of MEM-288 (n=3 DL1, n=5 DL2, n=3 DL3). No dose limiting toxicities have been reported to date and no pts have discontinued treatment due to toxicity. Treatment-related adverse events observed in >1 pt include grade 1 injection site reaction (45%) and chills (18%). Of 7 pts evaluable for response, 3 had shrinkage of injected tumor (range -40 to -54%), and multiple pts also had stabilization or shrinkage of distal non-injected lesions with best RECIST response in uninjected tumors as 2 SD and 5 PD. After a single MEM-288 injection, biopsies show decreased tumor cell percentage concomitant with substantial increases in overall CD8+ T cells, increased T clonotype diversity in both tumor and peripheral blood, and increased TCF1+ stem-like CD8+ T cells that are strongly associated with response to ICIs. Plasma cytokine analysis showed increases in IFNγ and of IFN-inducible cytokines and chemokines, supportive of stimulation of systemic response after MEM-288. Of note, a pt with strong stimulation of tumor and systemic T cell immunity after MEM-288 had a subsequent CR (ongoing >6 months) to docetaxel + ramucirumab following prior treatment failure with platinum doublet + ICI received before MEM-288. Conclusions: Preliminary safety, antitumor and immune response data are encouraging. Updated results and immune data will be presented. An expansion arm is planned with combination MEM-288 and anti-PD1 antibody in pts with advanced NSCLC refractory to ICI. Citation Format: Andreas N. Saltos, Christy Arrowood, Georgia Beasley, James Ronald, Ghassan El-Haddad, Uzma Khan, Luiziane Guerra-Guevara, Steven Wolf, Lin Gu, Xiaofei F. Wang, Dana Foresman, Xiaoqing Yu, Mark J. Cantwell, Scott J. Antonia, Amer A. Beg, Neal E. Ready. A phase 1 first-in-human study of MEM-288 oncolytic virus in solid tumors including non-small cell lung cancer (NSCLC): impact on tumor and systemic T cell immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT103.

e17081 Background: Intensification of androgen deprivation therapy (ADT) using novel hormonal therapies (NHT) has been established as a new standard of care for pts with mCSPC. Tx intensification still remains suboptimal, and data in de novo mCSPC pts is limited. Moreover, prior studies utilized claims data and so could not assess the impact of disease burden on Tx intensification. This study assessed baseline characteristics and 1L Tx patterns in pts with high-volume (HV) vs low-volume (LV) de novo mCSPC. Methods: This retrospective study used the Veterans Affairs Informatics and Computing Infrastructure to identify adult men who had ≥1 ICD code for prostate cancer and de novo mCSPC diagnosed between February 2018 and June 2020 confirmed by clinical chart review and initiated either ADT alone, ADT + first-generation non-steroidal anti-androgens [NSAA], or ADT+NHT. Index date was defined as ADT initiation date. The volume of disease was defined as HV or LV per the CHAARTED trial criteria (presence of visceral metastasis and/or ≥4 bone metastases, with ≥1 metastasis beyond the pelvis and vertebral column). Clinical data was hand abstracted from the medical record. Baseline characteristics and 1L Tx were analyzed descriptively. Results: Of the 380 de novo mCSPC pts reviewed, 57% had HV and 43% had LV disease. Mean age of pts was similar between HV and LV cohorts, 74.5 vs 75.2 years, respectively. In addition, the proportion of Black vs White pts in the HV and LV cohorts was similar, 34% and 35% were Black, and 66% and 65% were White, respectively. At index date, HV pts had higher median prostate-specific antigen (153.1 ng/mL vs 73.8 ng/mL) and alkaline phosphatase (192.0 IU/L vs 106.0 IU/L) vs LV pts. HV pts were less likely to have diabetes and cardiovascular comorbidities than LV pts (Table); however, the distribution of Charlson Comorbidity Index score was similar between cohorts (mean [SD]: 4.4 [3.1] vs 4.2 [3.1]). Among the pts with bone metastases only, HV pts had higher proportion (65%) of “too numerous to count” bone metastases vs LV pts (9%). While ADT+NHT use was slightly more common among HV pts (35%) vs LV pts (27%), in both HV and LV cohorts, ADT±NSAA was the most common 1L Tx (Table). The median 1L Tx duration was shorter in the HV pts compared with the LV pts (286 vs 358 days). Conclusions: The results showed that Tx intensification was underutilized in de novo mCSPC pts, even among those with HV, pointing toward an unmet need among pts with de novo mCSPC regardless of disease burden. [Table: see text]

Introduction: Most patients with advanced NSCLC will experience disease progression and death within 2 years. Novel approaches are needed to improve outcomes.Methods: We conducted an open-label, nonrandomized, phase 2 trial in patients with treatmentnaive, advanced NSCLC to assess the safety and efficacy of nivolumab 360 mg every 3 weeks, ipilimumab 1 mg/kg every 6 weeks, and four to six cycles of paclitaxel 80 mg/m2 on days 1 and 8 of every 21-day treatment. The primary end point of the study was median progression-free survival (PFS), with secondary end points of safety, objective response rate, and median overall survival (OS).Results: A total of 46 patients underwent consent and received treatment. The median age was 66 (range: 48-82) years, most had adenocarcinoma (63%), and 50% (23) had programmed death-ligand 1 greater than or equal to 1%. The median follow-up on the study as of October 2021 was 19 months. The primary end point of median PFS was 9.4 months (95% confidence interval [CI]: 5.9-16.6) in all patients regardless of programmed death-ligand 1 expression. The objective response rate for patients in the study was 47.8% (95% CI: 33.4-62.3). The 12-month OS rate was 69.5% (95% CI: 53%-81%), and median OS was not yet reached. Treatment-related grade greater than or equal to 3 adverse events was found in 54.3% of the patients.Conclusions: The toxicity observed was consistent with other reported chemo-immunotherapeutic combinations and was manageable. The primary end point of exceeding median PFS of 9 months was achieved with nivolumab, ipilimumab, and weekly paclitaxel and should be evaluated further in a randomized trial.(c) 2022 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).