Medical Oncology Hematology Consultants

707 Background: Since 2023, the combination of enfortumab vedotin and pembrolizumab (EV+P) has become a first-line (1L) non-chemotherapy (chemo) standard-of-care option for metastatic urothelial carcinoma (mUC). However, real-world (RW) data on clinical outcomes for EV+P remain limited. We evaluated RW clinical outcomes among patients (pts) with mUC treated with either EV+P or chemo in US community oncology practices in the 1L setting, as well as second-line (2L) utilization patterns of EV+P and chemo. Methods: We used the deidentified Integra PrecisionQ database to identify mUC patients initiating 1L EV+P or chemo after December 1, 2023. Index date was defined as the start of 1L therapy. Baseline pt characteristics collected include age at index date, sex, race, payer, ECOG performance status, and metastatic type (de novo metastatic disease vs. recurrent). Time to discontinuation (TTD) was defined as the time from the index date to 1L discontinuation or death. Time to next treatment (TTNT) was defined as the time from the index date to the date of any subsequent systemic treatment (2L) or death. Multivariable Cox proportional hazards regression modeling was performed to evaluate the association between treatment type and TTNT, adjusting for covariates. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) are presented. The distribution of 2L regimens was assessed for pts who initiated 2L therapy. Results: A total of 535 pts met study eligibility, of whom 406 (76%; median age [IQR]: 74 yr [67,81]) received EV+P as 1L therapy, and 129 received chemo (24%; median age [IQR]: 72 yr [65,79]). Overall, 91% of the cohort presented with de novo metastatic disease. The median follow-up for the study cohort was 4.7 mo (range: 0.03-18.9), during which 157/535 pts had died (EV+P: 117/406; chemo: 40/129). The table summarizes TTD and TTNT results. Of the 535 pts, 90 initiated 2L during the follow-up period, with most pts (32/46) who received 1L EV+P initiating chemo in the 2L setting. More than half of pts (24/44) who received 1L chemo received 2L EV+P. Conclusions: The adoption of EV+P as 1L therapy for mUC has been rapid since 2023 in US community oncology practices. Use of EV+P use was observed to be associated with longer time to 1L TTD and TTNT. Among pts who initiated 2L, EV+P treatment crossover between regimens is common. Median Time to Event (95% CI), mo Chemo (n=129) EV+P (n=406) logrank P value aHR for EV+P vs. chemo (95% CI) P value TTD 2.3 (1.9, 2.9) 5.9 (5, 7.5) <0.001 0.41 (0.31, 0.54) <0.001 TTNT 6.6 (3.3, 10.8) 9.7 (8.4, 10.6) 0.038 0.74 (0.55, 1.00) 0.051

175 Background: Lutetium-177 vipivotide tetraxetan (Lu 177) significantly improves progression-free survival (PFS) and overall survival (OS) in patients (pts) with pre-treated mCRPC. Combination strategies are being explored to enhance therapeutic outcomes. Preclinical models have demonstrated that radiotherapy selectively expands and activates regulatory T cells (Tregs) in the tumor microenvironment (TME). Gotistobart, an investigational pH-sensitive anti-CTLA-4 antibody, enhances Treg depletion in the TME and, combined with Lu 177, has demonstrated manageable safety and promising preliminary PSA50 rates in pts with mCRPC (#5067, ASCO 2025). Here, we report updated efficacy analyses from this Phase 1 trial. Methods: PRESERVE-006 (NCT05682443) is an open-label, randomized, phase 1/2 trial evaluating gotistobart with Lu 177 in pts with mCRPC post-androgen receptor pathway inhibition. Pts received gotistobart (3 mg/kg Q4W, 6 mg/kg Q6W, or 10 mg/kg Q6W, up to 13 doses) plus Lu 177 or Lu 177 alone (up to 6 doses). Efficacy endpoints were assessed per PCWG3 guideline. Results: As of August 8, 2025, this Phase 1 enrolled 25 pts who had a median age of 69 years (range: 52–86), 64.0% of the pts were White, 24.0% were Black and 4.0% were Asian. All pts had prior taxane and androgen receptor pathway inhibitors. Safety data for all 25 pts were reported at ASCO 2025, and no new safety signals were observed. With a median follow-up time of 11.9 m, median radiographic PFS (rPFS) was 4.8 m, 12.2 m, 8.3 m and not reached in the Lu 177 only, 3 mg/kg combo, 6 mg/kg combo, and 10 mg/kg combo group, respectively (Table). Among the 7 pts with measurable disease at baseline who received combination therapy, 5 (71.4%) achieved a partial response, and 2 pts achieved stable disease. Median PSA PFS was not reached for the cohorts dosed at 3 mg/kg and 6 mg/kg. Conclusions: Preliminary efficacy with a manageable safety profile was observed for gotistobart in combination with Lu 177 in pts with mCRPC during the Phase 1 study. The three arm randomized Phase 2 dose optimization stage (n=122) has completed enrollment at the 3 mg/kg combo, 6 mg/kg combo and Lu 177 only groups. Clinical trial information: NCT05682443 . Gotistobart 3 mg/kg + Lu 177(N = 6) Gotistobart 6 mg/kg + Lu 177(N = 6) Gotistobart 10 mg/kg + Lu 177(N = 6) Lu 177(N=7) Median follow-up time, m 17.8 9.2 11.9 12.3 Confirmed PSA50, n (%) (95% CI) 4 (66.7) (22.3, 95.7) 3 (50.0)(11.8, 88.2) 3 (50.0) (11.8, 88.2) 2 (28.6) (3.7, 71.0) PSA90, n (%) (95% CI) 3 (50)(11.8, 88.2) 0 (0.0, 45.9) 2 (33.3)(4.3, 77.7) 1 (14.3)(0.4, 57.9) Median rPFS, m(95% CI) 12.2(2.0, NE) 8.3(5.8, NE) Not reached (11.0, NE) 4.8(3.8, NE) 6m rPFS rate, (%) (95% CI) 66.7(28.9, 100) 75.0(32.6, 100) 83.3(53.5, 100) 28.6(0, 62.0) Median PSA-PFS, m (95% CI) Not reached(9.72, NE) Not reached (5.39, NE) 10.4(4.8, NE) 4.9(4.4, 6.0)

This systematic review and meta-analysis compared the diagnostic performance of MRI, [ 18 F]FDG-PET/CT, and [ 18 F]FDG-PET/MRI in detecting focal bone lesions and bone marrow infiltration in the initial staging of patients with multiple myeloma (MM) who underwent both MRI and [ 18 F]FDG-PET/CT or [ 18 F]FDG-PET/MRI studies. A systematic literature search was conducted across PubMed, Embase, and Cochrane databases, including studies comparing the performance of MRI (WB-MRI or spine/pelvis MRI), [ 18 F]FDG-PET/CT, and/or [ 18 F]FDG-PET/MRI in the same patients for MM initial staging. Pooled sensitivities and concordance between imaging modalities were analyzed using R (package META-R). Heterogeneity and bias were assessed with the QUADAS-C tool. Twenty studies (published between 2007 and 2025) using the international MM diagnostic criteria as a reference standard met the inclusion criteria. Of these, 13 (n=742) compared per-patient sensitivity of [ 18 F]FDG-PET/CT and MRI, and 4 (n=224) compared MRI and [ 18 F]FDG-PET/MRI. Pooled sensitivities were 0.807 (95% CI: 0.74-0.86) for [ 18 F]FDG-PET/CT (with significant heterogeneity) versus 0.914 (95% CI: 0.88-0.94) for MRI (0.906 for spine/pelvis MRI and 0.920 for WB-MRI) ( P <0.001 for meta-regression analysis). Using contingency tables, 83% (599/721) of included patients had concordant [ 18 F]FDG-PET/CT and MRI results, while 14% (101/721) patients had negative [ 18 F]FDG-PET/CT and positive MRI with significant differences between the 2 techniques for the paired sample analysis ( P <0.001). The pooled sensitivity of the 4 studies including [ 18 F]FDG-PET/MRI was 0.944 (95% CI: 0.88-0.98). Consensus definitions for specificity in MM imaging should be standardized across studies. This systematic review and comparative meta-analysis demonstrates superior sensitivity of WB-MRI compared with [ 18 F]FDG-PET/CT for initial staging of MM patients. Future international guidelines might prioritize MRI and [ 18 F]FDG-PET/MRI for staging of MM patients. PROSPERO CRD42024564937.

Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PD-L1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups. Associations with real-world progression-free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 IHC treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups [IRS-L divided into IRS-Ultra-Low (-UL) and Intermediate-Low (-IL), and similarly assessed]. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H versus IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy versus chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 versus anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment.Significance:This study confirms the utility of the integrative IRS biomarker for predicting anti-PD-L1/PD-1 benefit. IRS significantly improved upon currently available biomarkers, including PD-L1 IHC, TMB, and MSI status. Additional utility for informing on chemotherapy, anti-PD-L1/PD-1, and anti-PD-L1/PD-1 plus chemotherapy treatments decisions is shown.

TPS3172 Background: Ulixertinib (BVD-523) is a small molecule inhibitor of extracellular signal-regulated kinases 1/2 (ERK1/2) in development as a novel anti-cancer drug. Early clinical data demonstrated anti-tumor activity, especially for patients with tumors harboring atypical BRAF or MEK1/2 alterations (Sullivan et al., Cancer Discov. 2018;8(2):184-195). Atypical BRAF (non-V600) alterations can be categorized according to characteristics of molecular signaling (Class II or III), are seen in approximately 3% of all human cancers, and there are currently no approved therapies for this indication. Similar to atypical BRAF alterations, the incidence of MEK1/2 alterations are rare in human tumors (&lt; 1 %). Preclinical data have demonstrated activity of ulixertinib in MEK mutant models. Ulixertinib has FDA fast-track designation for patients with solid tumors, other than CRC, with specific BRAF mutations (G469A, L485W, or L597Q). Designed with intent to register, the BVD-523-ABC clinical trial will continue evaluation of ulixertinib in patients with tumors harboring any atypical BRAF or MEK1/2 alteration (NCT04488003). Methods: This multi-center, phase II study, will be conducted in two parts and assess the clinical benefit, safety, pharmacokinetics, and pharmacodynamics of ulixertinib in patients with advanced malignancies. Ulixertinib will be administered at the RP2D of 600 mg BID for 28-day treatment cycles. Eligible patients will have locally advanced or metastatic cancer which progressed following standard systemic therapies, or for which the patient is not a candidate or refused systemic therapy. Planned correlative analyses include reverse phase protein array and transcriptomics of tumor tissue. Part A is open-label and tumor agnostic, except for group 4 and 6 (CRC patients only). Patients will enroll into one of six groups based on BRAF (groups 1-4) or MEK1/2 (groups 5-6) tumor alteration (38 patients per group). Overall response rate (ORR) is the primary endpoint for Part A, with secondary endpoints including duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Part B is tumor histology specific. Patients will be randomized to receive either ulixertinib or physician's choice of treatment in a 2:1 ratio. Up to three specified tumor histologies will be defined, guided by available Part A data (n = 80-100 per histology). The primary endpoint of Part B is PFS, and secondary endpoints include OS, ORR, and DOR. This study has enrolled 43 patients of the planned 228 in Part A at the time of abstract submission. Clinical trial information: NCT04488003.

2008 Background: Enthusiasm for precision oncology may obscure the complex psychosocial and ethical considerations for tumor genetic testing. Low patient genetic knowledge has been documented and heightens the risk for adverse experiences. We developed a web-based intervention to increase genetic knowledge and decrease distress among advanced cancer patients undergoing tumor genetic testing. Methods: 594 patients (80% from NCORP Community Sites) were recruited and randomized to web-intervention (n = 293) or usual care (n = 301), prior to receipt of tumor genetic test results. Primary outcomes were genetic knowledge, anxiety, depression, and cancer-specific distress measured at T0 (prior to intervention), T1 (post-intervention), T2 (after receipt of tumor results) and T3 (3 months post receipt of tumor results). Secondary outcomes included satisfaction, regret and disappointment. The effect of web-intervention was evaluated using t-test, multiple linear regression and logistic regression, with an intent-to-treat approach. Results: Patients randomized to web-intervention had better knowledge improvement than those randomized to usual care (T1-T0, p &lt; 0.0001; T2-T0, p = 0.003). No difference was observed in change scores for anxiety, depression or cancer-specific distress. To find the moderators of intervention effect (including sex, age, education, and literacy) two 2-way interactions were noted with statistical significance: higher depression among those in the intervention arm versus the control arm for patients with lower literacy (p = 0.03); and lower cancer-specific distress among women in the intervention arm than with usual care but no such effect noted in men (p = 0.01). 71% of patients reported receiving tumor test results and this did not differ by arm. Only 20% of patients reported regret and disappointment at T2, which was more likely for those without a mutation of interest (MOI) detected vs those with a MOI detected (OR = 2.08, 95% CI, 1.13 to 3.83, p = 0.02). Conclusions: Web-based education prior to receipt of tumor genetic test results increases patient understanding of tumor genetic testing. While the intervention did not significantly reduce distress, results suggest that women who received the intervention had lower cancer-specific distress than those with usual care. Future refinements to the web-intervention are needed to address low literacy groups, men and patients with no actionable results. Clinical trial information: NCT02823652.

214 Background: Best practices of cancer care delivery have shifted from medical models to interdisciplinary approaches aimed at holistic care. The social work profession has advanced itself by gaining competence in psycho-oncology, advance care planning, biopsychosocial assessment and intervention, and pain management. While Masters prepared Social Workers (MSW) are widely recognized as experts in most of these areas, it appears that they are underutilized in pain management. This study will examine provider and nursing perceptions about social work expertise and whether those perceptions may limit utilization of social work in multidisciplinary management of cancer pain. Methods: While review of psycho-oncology literature supports the role of social work in pain management, this was not clearly indicated within the medical oncology domain. A survey was created to ascertain the perception of the MSW role in pain management as a supplement to pharmacologic and medically-based care when identifying and treating multidimensional pain. The survey was completed by Physicians, Advanced Practice Providers, and Nurses in outpatient oncology practices in The US Oncology Network. Results: 139 medical professionals responded. As hypothesized, 88% reported they were comfortable with MSWs conducting Advance Care Planning, while 61% reported being comfortable with MSWs educating patients and families about pain management during palliative/end of life care. 95% believed unmet emotional, social, spiritual and existential needs can present as physiological pain, however only 55% indicated they would include Licensed Clinical Social Workers to provide therapeutic interventions as part of pain management. Conclusions: Under half of survey participants reported an understanding of the scope of social work practice, which aligns with the lack of awareness and under-utilization of social work as a vital contributor in oncologic pain management. MSWs have training in evidence-based interventions such as CBT, guided imagery, mindfulness and biofeedback techniques which may diminish the experience of pain. Further research is recommended to identify strategies to promote and integrate social work into multidisciplinary pain management.