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4565 Background: EVP is the preferred 1 st -line regimen for patients (pts) with aUC. EV-related toxicities are often managed with dose adjustments, such as reductions and holds. Analysis of EV monotherapy trials showed consistent survival outcomes despite dose adjustments. We hypothesized that on-treatment EV dose adjustments would not impact survival in these pts. Methods: Pts with aUC treated with EVP in the multisite UNITE study were analyzed. Early dose reductions (DR) and holds were defined as occurring < 9 weeks from EVP start, with the remainder classified as late. Pts with DR at treatment start were excluded. Survival endpoints were progression-free survival (PFS) and overall survival (OS) from EVP start, assessed by Kaplan-Meier analysis and Cox models. Multivariable Cox analysis (MVA) included age (≥ 75 vs < 75), ECOG performance status (0-1 vs 2-3), Hgb level (< 10 vs ≥ 10) and liver metastases (present vs not). A time-dependent covariate was used to reduce immortal time bias. Complementary MVA landmark analyses were performed, aligned to the total number of treatment cycles received, with six analyses from cycles 2 to 7. Results: 360 pts from 17 sites were included (median age 70; 78% Caucasian; 76% male; 27% upper tract primary; 35% histology subtype component; 17% with liver metastasis; 78% frontline); median follow-up was 11.7 months (95% CI [10.79, 13.08]). Median number of cycles was 6 in pts with DR and 3 with no DR. Early DRs (100 pts [28%]) and holds (18 pts [5%]) were most commonly due to rash (28% of all early DRs and holds). Late DR (75 pts [21%]) and holds (50 pts [14%]) were most commonly due to neuropathy (52% of all late DRs and holds). Pts with early or late DR had longer PFS and OS vs those who did not (Table); however, there was no significant PFS or OS difference with dose hold vs no hold (PFS HR 0.65, 95%CI (0.40, 1.05), p = 0.08; OS HR 0.70, 95%CI (0.39, 1.27), p=0.24). In landmark analyses, about 50% of pts had DR; no significant difference in PFS or OS was observed at most landmarks, except for longer OS in the DR cohort at cycle 4 (HR 0.53, 95% CI (0.29, 0.98), p = 0.042) and cycle 5 (HR 0.43, 95% CI (0.19, 0.99), p = 0.048). Conclusions: In this real-world retrospective analysis, EVP efficacy was maintained despite DR and dose holds. Survival difference noted in the time-dependent analyses were not consistently reproduced in landmark analyses, suggesting exposure-related selection bias rather than causal effect. Prospective studies are warranted to validate these hypothesis-generating findings. Association of EV DR with PFS/OS (time-dependent analyses). Early DR Late DR DR vs no DR outcomes UVAHR (95% CI), p MVAHR (95% CI), p UVAHR (95% CI), p MVAHR (95% CI), p PFS 0.50 (0.35, 0.72), <.001 0.56 (0.38, 0.84), 0.005 0.32 (0.21, 0.49), <.001 0.36 (0.23, 0.57), <.001 OS 0.51 (0.32, 0.79), 0.003 0.57 (0.35, 0.92), 0.022 0.26 (0.15, 0.45), <.001 0.31 (0.17, 0.55), <.001

4515 Background: Adenocarcinomas of the urinary tract are rare malignancies with limited prospective data. Outcomes of triplet chemotherapy remain poorly defined. Methods: This was a prospective, single-arm, phase II study (NCT00082706) conducted at MD Anderson. Between 2005 and 2010, patients (pts) aged ≥18 years with ECOG 0–2 and metastatic or unresectable urachal (UA) or non-urachal adenocarcinoma (NUA) received frontline GemFLP (5-fluorouracil 200 mg/m² continuous infusion ×5 days with leucovorin 23 mg IV daily ×5; cisplatin 20 mg/m² IV daily ×5; gemcitabine 200 mg/m² IV on days 1 and 5). Best overall response (BOR) was assessed by imaging. Primary endpoints were objective response rate (ORR) and overall survival (OS); secondary endpoint was toxicity. PFS was calculated from treatment initiation and duration of response (DoR) from first CR/PR to progression or death; time-to-event endpoints were estimated by Kaplan–Meier (KM). Post hoc analyses evaluated baseline tumor markers (CEA, CA19-9, CA125, β-hCG) Treatment-related adverse events (TRAEs) were graded per CTCAE v5. Results: Forty-six pts were enrolled (28 UA, 18 NUA). Median age was 58 years; 41% were de novo metastatic, and 78% had visceral metastases. ORR was 44% (20/46). Among responders, median DoR was 8.6 months (95% CI 4.6–30.8). median PFS was 3.3 months (95% CI 2.3–8.4) and median OS (mOS) was 21.0 months (95% CI 15.9–35.3) There was no difference in PFS (p=0.39) or OS (p=0.99) between UA and NUA. Baseline CEA, CA19-9, CA125, and β-hCG were not associated with ORR or PFS. Higher baseline CA125 was associated with inferior OS (HR 1.33, 95% CI: 1.12–1.58; p =0.001) Subsequent systemic therapy was administered to 28 pts (60.9%); median number of subsequent treatment lines was 2 (range 1–5). The most common hematologic TRAEs were anemia (28.1%; grade ≥3 [G3] 12.5%), thrombocytopenia (21.9%; G3 12.5%), and neutropenia (12.5%; G3 9.4%). The most frequent non-hematologic TRAEs were dehydration (21.9%; G3: 6.2%), diarrhea (9.4%; G3 6.2%) and catheter-related thrombosis (9.4%; G3 9.4%). No grade 5 events occurred. Conclusions: In this prospective phase II study, frontline GemFLP achieved a 44% ORR with durable responses (mDoR 8.6 mo) and 21 mo mOS in advanced UA and NUA. Survival did not differ between UA and NUA subtypes. Baseline CA125 was associated with OS. Toxicity was manageable. These data provide a prospective benchmark for this rare disease. Clinical trial information: NCT00082706 . Variable UA (n=28) NUA (n=18) Characteristics Age, median [ICR] 58 [54– 62] 58 [54– 62] 67 [ 62-72] Race, n (%) White 22 (79) 11 61) Black 6 (21) 6 (33) Other 0 1 (6) Prior surgery for localized disease, n (%) 18 (64) 5 (28) Mets at baseline Any 24 (86) 7 (39) Lung 6 (21) 4 (22) Liver 3 (11) 0 Peritoneum 17 (61) 0 Bone 3 (11) 3 (17) Nodal-only mets 1 (3) 2 (10) Outcomes ORR (%) 43.5 35.7 55.6 BOR n (%) CR 4 (14) 2 (11) PR 6 (21) 8 (44) SD 11 (39) 4 (22) PD 6 (21) 3 (17) NE 1 (4) 1 (6)

4178 Background: In the CABINET trial, CABO significantly prolonged progression-free survival (PFS) compared to placebo (PB) in patients (pts) with advanced, previously treated extrapancreatic NET (epNET) or pancreatic NET (pNET) (Chan et al., NEJM, 2025). Here we report outcomes according to functional status based on NET hormone secretion. Methods: Pts with locally advanced or metastatic epNET or pNET were randomized 2:1 in separate cohorts to receive CABO 60 mg daily vs PB. Eligibility included progression by RECIST within 12 months (mo) before registration, ≥ 1 prior systemic therapy not including somatostatin analogs (SSA). Pts with functional NET due to hormone secretion and non-functional NET were included. In this post hoc subgroup analysis, we analyzed PFS by blinded independent central review and adverse events for pts receiving CABO vs PB based on functional status. Cox regression models were used with stratification on primary tumor site (epNET vs pNET). Subset analyses to evaluate treatment arm differences were conducted in pts with functional and non-functional tumors. Due to small numbers, separate results for those with unknown functional status are not included. Results: Of the total 298 pts enrolled in both cohorts, 74 had a functional NET (CABO, n = 47; PB, n = 27); 179 had a non-functional NET (CABO, n = 123; PB, n = 56); 45 had unknown functional status (CABO, n = 28; PB, n = 17). For functional NET, primary tumor sites were GI tract (n = 50; 68%), pancreas (n = 15; 20%), unknown (n = 4; 5%), lung (n = 3; 4%), and thymus (n = 2; 3%). Secreted hormones that were reported included serotonin (55%), somatostatin (18%), gastrin (16%), glucagon (4%), insulin (4%), ACTH (1%), and vasoactive intestinal peptide (1%). For non-functional NET, primary tumor sites were pancreas (n = 75; 42%), GI tract (n = 42; 23%), lung (n = 30; 17%), unknown (n = 17; 9%), thymus (n = 8; 4%), and other (n = 7; 4%). Concurrent SSA was received by 91% and 53% of pts with functional and non-functional NET, respectively. In both subgroups, CABO was associated with improved PFS compared to PB (for functional NET: stratified hazard ratio [sHR], 0.40; 95% confidence interval [CI]: 0.20-0.82, P = 0.012; for non-functional NET: sHR, 0.26; 95% CI: 0.17-0.41, P < 0.001). The most frequent grade 3/4 adverse events (AEs) attributed to CABO vs PB in pts with functional NET included hypertension (21% vs 11%), diarrhea (9% vs 11%), and fatigue (2% vs 15%); in pts with non-functional NET, grade 3/4 AEs included hypertension (21% vs 4%) and fatigue (18% vs 4%). Conclusions: Subset analyses of the CABINET trial suggest that CABO is an effective treatment option for pts with functional and non-functional epNET or pNET. Efficacy and safety results for pts with functional or non-functional NET treated with CABO are consistent with results for the entire trial. Clinical trial information: NCT03375320 .

4013 Background: Pancreatic ductal adenocarcinoma (PDAC) is driven predominantly by oncogenic KRAS signaling, yet prior attempts to target the MAPK pathway have been limited by toxicity and emergence of resistance. Atebimetinib is a next-generation, deep cyclic inhibitor (DCI) of MEK designed to achieve pulsatile pathway inhibition with improved tolerability. We report a Phase 2a cohort evaluating atebimetinib in combination with modified gemcitabine/nab-paclitaxel (mGnP) in the first-line treatment of advanced or metastatic PDAC (NCT05585320). Methods: In this multicenter, open-label, nonrandomized Phase 2a study, patients with previously untreated advanced or metastatic PDAC were eligible for participation and were treated with orally administered atebimetinib daily in combination with mGnP (modification: every other week dosing). The primary endpoint was objective response rate (ORR) per investigator assessment using RECIST 1.1 criteria in response-evaluable patients. The cohort was powered (~80%, one sided alpha 0.05) using an optimal Simon’s 2-stage design. Results: Fifty-five patients were enrolled and treated with 320 mg atebimetinib daily + mGnP. ECOG performance status was 0-1 (100%); median age was 68 years (range 42-85 years), 62% were ≥65 years, and 55% were male. No grade 5 treatment-related adverse events (AE) were observed. No AE related to atebimetinib were higher than grade 3. Grade 3 AE related to atebimetinib occurred in 29% of participants, with the most frequent being rash (5%), ALT increased (5%), and AST increased (5%). Among the 50 response-evaluable patients, best overall response (BOR) achieved were 21 PR, 21 SD, 7 PD, 1 NE. The ORR was 42%, and DCR was 84%. With a median follow-up of 10.4 months (data cutoff Jan 7, 2026), 6- and 9-month OS rates were 88% and 79%, respectively; median PFS was 8.3 months and median OS was not reached. Conclusions: Atebimetinib in combination with mGnP demonstrated favorable safety and promising efficacy compared to historic standard-of-care (SoC) GnP. 1 A phase 3 registrational trial is planned to start in mid-2026 for evaluation of atebimetinib + mGnP versus SoC GnP. 1. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med . 2013;369(18):1691-1703. doi:10.1056/NEJMoa1304369 (PMID: 24131140). Clinical trial information: NCT05585320 .

3146 Background: The MTA-cooperative PRMT5 inhibitor BMS-986504 selectively binds to the PRMT5-MTA complex, a synthetic lethal target in MTAP -del cancer cells, while sparing MTAP –wild-type normal cells. In the phase 1 CA240-0007 study, BMS-986504 was well tolerated and had antitumor activity in pts with MTAP -del advanced solid tumors (ORR, 23%; median DOR, 10.5 mo). BMS-986504 also demonstrated dose-dependent reductions in plasma symmetric dimethylarginine (SDMA) levels, a PD biomarker of PRMT5 inhibition. Here, we report expanded PD and genomic analyses and initial results of exploratory proteomic analyses from CA240-0007. Methods: Pts with advanced, unresectable, or metastatic solid tumors with homozygous MTAP -del received BMS-986504 (50–800 mg) in 3-wk cycles. Analyses of SDMA levels and proteomic profiles from paired plasma samples (baseline and C2D1) were performed using mass spectrometry and SomaScan 11K, respectively. Tumor genomic information was extracted from local pathology reports. ORR was assessed per RECIST v1.1. Results: Among 78 pts with paired samples at data cutoff (22 Sept 2025; median f/u, 15.9 mo), dose-dependent reductions were seen in plasma SDMA levels, with the greatest reductions at 400 mg QD (median, 60.3%; n = 31) and 600 mg QD (median, 60.3%; n = 23). Proteomic pathway enrichment analysis demonstrated downregulation of PI3K/Akt/mTOR, Myc target, cell cycle, and DNA damage repair (DDR) pathways with BMS-986504 on C2D1 (n = 87), consistent with the expected effect of PRMT5 inhibition; a trend toward deeper modulation of PRMT5-regulated pathways was observed at higher doses. No proteins at baseline (n = 94) were found to be significantly associated with ORR (false discovery rate > 0.05). Responses in clinically evaluable pts with NSCLC (n = 33) or PDAC (n = 35) were observed regardless of EGFR , KRAS , or TP53 status. In pts with NSCLC, STK11 and SMARCA4 alterations were numerically higher in nonresponders. No gene alterations were associated with response in PDAC, except GABRA6 alterations (n = 2, both responders). A trend toward higher ORRs was seen in pts with alterations in DDR genes ( CHEK2, FANCD2, XRCC4 , and/or MSH2 ), consistent with the role of PRMT5 in DDR via regulation of mRNA splicing. ctDNA analysis will be presented. Conclusions: BMS-986504 demonstrated robust dose-dependent PD effects in pts with advanced solid tumors in plasma SDMA and proteomic analyses. Downregulation of PRMT5-regulated pathways was observed with BMS-986504 treatment. Response was seen regardless of EGFR, KRAS , and TP53 alterations in NSCLC or PDAC, and DDR gene alterations were associated with improved response. These findings further support the MOA of BMS-986504 and its ongoing investigation in the phase 2/3 MountainTAP-9, -29, and -30 studies as a potential treatment option in pts with MTAP -del advanced solid tumors. Clinical trial information: NCT05245500 .

3510 Background: Patients with RAS-mutated mCRC have limited treatment options. Chemotherapy in combination with bevacizumab (Bev) has been the standard first-line treatment for the past two decades, yet the prognosis for these patients remains poor. Onvansertib (Onv), a selective PLK1 inhibitor, has previously demonstrated synergy with chemotherapy in the second line setting. The Phase 2 randomized CRDF-004 trial evaluated onvansertib plus standard-of-care (SoC; FOLFIRI or FOLFOX with Bev) in as first-line RAS-mutated mCRC. Methods: Patients with first-line KRAS or NRAS mutant mCRC were randomized to SoC alone or SoC plus onvansertib (20 mg or 30 mg). The primary endpoint was objective response rate (ORR) as determined by a blinded-independent central review (BICR) using RECIST v1.1. Key secondary endpoints included progression-free survival (PFS), duration of response, and safety. PFS was assessed by BICR and investigator assessments combined. Results are presented in the intent-to-treat population (ITT). Results: At the data cutoff of 22 Jan 2026,110 patients were randomized with a median follow up of approximately 10 months. Baseline characteristics were relatively balanced across arms. Onv 30 mg + FOLFIRI + Bev demonstrated numerically higher ORR (n = 13/18, 72.2%, 95% CI: 46.5, 90.3) compared with the FOLFIRI + Bev control arm (n = 8/19, 42.1%, 95% CI: 20.3, 66.5), the FOLFOX + Bev control arm (n = 8/18, 44.4%, 95% CI: 21.5, 69.2) and the combined control arms (SoC: n = 16/37, 43.2%, 95% CI: 27.1-60.5). Onv 30mg + FOLFIRI + Bev demonstrated a p-value of 0.051 for confirmed ORR vs. SoC; and a p-value of 0.045 for the 6-month ORR compared to FOLFIRI + Bev (n = 10/18, 55.6%, 95% CI: 30.8-78.5 vs. n = 4/19, 21.1%, 95% CI: 6.1-45.6, respectively). The median PFS for the control arms was 10.97 months (95% CI: 7.52, NR) for FOLFIRI + Bev, 9.89 months (95% CI: 9.43, NR) for FOLFOX + Bev and 10.97 months (95% CI: 9.43-15.44) for the combined SoC arms. The median PFS in the Onv 30mg+ FOLFIRI + Bev arm was not reached (95% CI: 9.72-NR). The PFS HR of 30mg + Onv +FOLFIRI + Bev vs FOLFIRI + Bev was 0.38 (95% CI: 0.12-1.17) and vs SoC was 0.37 (95% CI: 0.13-1.02, p = 0.048). The clinical benefit from Onv treatment was further evidenced by the 12-month PFS rates, 61.9% (95% CI: 40.1, 95.8) in the Onv 30 mg + FOLFIRI + Bev arm vs. 28.4% (95% CI: 9.3, 86.9) in the FOLFIRI + Bev arm, and 30.1% (95% CI: 13.8-65.7) in the SoC. Onvansertib was well tolerated, with no unexpected toxicities observed; the most common grade ≥3 adverse event was neutropenia. PK data support moving forward with the onvansertib 30mg dose with FOLFIRI + Bev. Conclusions: Onvansertib plus FOLFIRI and bevacizumab demonstrated improved antitumor activity and manageable safety in first-line RAS-mutated mCRC. These results support further clinical and support planned confirmatory Phase 3 evaluation. Clinical trial information: NCT06106308 .

3109 Background: Poly(ADP-ribose) glycohydrolase (PARG) is an enzyme that catalyzes the removal of poly-ADP-ribose (PAR) chains from proteins during DNA damage repair. PARG inhibition leads to selective cell death in tumors with underlying replication fork defects, including BRCAm tumors, through a mechanism distinct from PARP inhibition. ETX-19477 is an oral, potent, and selective PARG inhibitor that shows robust preclinical activity in mouse models of ovarian, breast, and gastric cancers. Methods: ERADIC8 is an open-label, multicenter, Phase 1/2 study, consisting of two parts, dose escalation and dose expansion. A Bayesian Optimal Interval Design was used to enroll patients (pts) into dose escalation cohorts, with enrichment for pts with BRCAm high grade serous ovarian (HGSOC) and breast cancers. The primary objective is to assess safety/tolerability of ETX-19477 and define the maximum tolerated dose (MTD) and recommended Phase 2 dose(s). Secondary and exploratory objectives include pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity per RECIST v1.1. ETX-19477 is given orally once or twice daily in 21-day cycles. Results: As of Jan 6 2026, 45 pts were enrolled into the study across 11 dose levels (range: 80-750 mg QD, 190-350 mg BID). Tumor types included ovarian (n=24, BRCAm: 18), breast (n=8, BRCAm: 7), endometrial (n=6, BRCAm: 0), colorectal (CRC, n=3, BRCAm: 1), and other (n=4, BRCAm: 0) cancers. Treatment-related AEs (TRAEs; any grade) occurring in >20% of pts were nausea (53%), vomiting (38%), and fatigue (24%). The only Gr3 TRAE occurring in >5% of pts was neutropenia (16%). There was one Gr4 TRAE of neutropenia in 1 pt (2%) and no Gr5 TRAEs. ETX-19477 exposure is dose proportional, and the BID regimen achieves >85% PARG inhibition throughout the dosing interval in a blood-based PAR accumulation pharmacodynamic assay. As of the data cutoff, dose escalation is ongoing at 350 mg BID (MTD has not been defined) and dose expansion is ongoing at 200-300 mg BID. Among BRCAm, HGSOC pts enrolled at BID dose levels, there were 7 evaluable pts with a median of 4 prior lines of therapy (range 2–11): 2 pts achieved a partial response (PR, 29%) and 3 pts achieved stable disease (SD, 43%). Both pts with PRs were platinum-resistant and received prior PARP inhibitor treatment. 1 pt with BRCAm CRC remains on active therapy (250 mg BID) with SD for 7 months. Conclusions: ETX-19477 was well tolerated and showed anti-tumor activity in heavily pretreated pts with BRCAm, platinum-resistant HGSOC during dose escalation. These findings provide the first clinical proof-of-concept of PARG inhibition in HGSOC. ETX-19477 is being further evaluated in the dose expansion phase of the study. Clinical trial information: NCT06395519 .

3014 Background: Macrocyclic next-generation tyrosine kinase inhibitors (TKIs) have transformed outcomes in ALK- and ROS1-positive NSCLC; such creatively designed medicines are similarly needed to improve outcomes in EGFR-mutant NSCLC. Using a novel, mutant-selective macrocyclic structure, BH-30643 was designed for super-potency against driver EGFRm, largely sparing wildtype (WT) EGFR, and with unique invulnerability to resistance from C797S with or without T790M. Here we report emerging first-in-human dose-escalation data from the SOLARA trial (NCT06706076). Methods: Phase 1 dose escalation used a BOIN design with backfill at potentially efficacious doses. Expansion cohorts targeted populations of interest. Patients (pts) had advanced NSCLC with EGFR and/or HER2 mutations detected on local testing (tissue or plasma). Measurable disease was required; asymptomatic untreated brain metastases (BM) were permitted. Objectives included safety, PK, and RECIST response rate (ORR). Plasma NGS was performed at baseline and on treatment. Results: As of 01/05/2026, 72 pts enrolled into dose escalation and backfill across 7 dose levels at a total daily dose of 20mg -160mg, median age 62, 44% Asian, 65% with history of BM, median of 3 prior lines of treatment (range 1-12). EGFR mutations included classical (38 pts), exon20ins (14 pts) and other/atypical (18 pts) or HER2 mutations (2 pts). Plasma exposures at doses of 40mg BID and above achieved > 10x coverage over target EC90 and exceeded exposure levels of most contemporary EGFR TKIs. Common TRAE ( > 10%) were WT EGFR-associated, including diarrhea (38%), rash (28%), fatigue (15%), stomatitis (13%), and were predominantly grade 1. Bilirubin elevation was seen in 26 pts (36%) related to off-target UGT1A1 inhibition (Gilbert’s-like). Grade 3 TRAE were seen in 15 pts (18%), most commonly bilirubin (8/15); DLTs included bilirubin increase and mucositis, occurring at doses ≥ 60mg BID. No pneumonitis was observed. Responses were observed across diverse EGFRm subsets, including in CNS. Including expansion pts, 28 pts enrolled with C797S on their most recent informative molecular testing (6 with concurrent MET+ or KRAS+), with 23 still on therapy. Of 17 with on-treatment scans, partial responses (confirmed or ongoing) were seen in 10 (59%); ORR was comparable with (50%) or without (66%) T790M. Of 9 pts with baseline C797S detected in ctDNA (3 with T790M), 7 had > 99% reduction of C797S VAF on treatment. Conclusions: Leveraging a novel macrocyclic scaffold, BH-30643 is the first TKI monotherapy to demonstrate clinical responses against C797S both with or without T790M. High plasma exposures combined with super-potency, CNS activity, and favorable safety offers potential for deep and durable EGFR inhibition. Enrollment into backfill and expansion cohorts is ongoing to better characterize activity in both TKI-naïve and resistant pts. Clinical trial information: NCT06706076 .

11502 Background: To report results from the open-label alveolar soft part sarcoma (ASPS) cohort of the phase III APROMISS trial (NCT03016819) evaluating Catequentinib hydrochloride (AL3818), an oral multitargeted receptor tyrosine kinase inhibitor, in adults with advanced or metastatic ASPS. Methods: Adult patients with pathologic and molecularly confirmed advanced ASPS, either treatment-naive or previously treated (excluding cediranib), were enrolled in the open-label, non-randomized ASPS cohort of the phase III APROMISS trial conducted across the United States, Asia, and Europe. Catequentinib hydrochloride was administered orally at 12 mg once daily in 21-day cycles (14 days on/7 days off) until disease progression, toxicity, or death. The primary endpoint was objective response rate (ORR) assessed per RECIST by Blinded Independent Central Review (BICR) (predefined threshold: 31%). Secondary endpoints included duration of response (DOR) with a predefined target of =/>6 months, progression free survival (PFS) and overall survival (OS). Results: From July 2017 to August 2022, a total of 56 patients entered the trial; 56 patients were evaluable for the primary endpoint. Median (m-) age was 29.5 years (range: 18 – 66), with 24 female and 32 male. Best overall response included 1/56 complete response (1.8%), 14/56 partial responses (25.0%), 36/56 stable disease (64.3%), and 3/56 (5.4%) progressive disease. RECIST ORR by BICR was 26.8% (95% CI, 15.8–40.3); m-DOR was 22.57 months (95%CI: 10.38-NE). The study data was collected close to 8 years for all patients. mPFS was 18.33 months (95% CI, 14.19–23.13), with 6- and 12-month progression-free rates of 88.77% (95% CI, 76.68–94.79) and 65.54% (95% CI, 50.42–77.06), respectively. mOS was 59.27 months (95% CI, 44.09–NE), with 6- and 12-month overall survival rates of 94.64% (95% CI, 84.30–98.24) and 90.81% (95% CI, 79.30–96.08), respectively. Overall, 27/56 (48.2%) patients experienced grade ≥3 treatment-related adverse events, most commonly diarrhea (50.0%), hypertension (44.6%), fatigue (37.5%), nausea (35.7%), and palmar-plantar erythrodysesthesia syndrome (30.4%); one patient (1.8%) had a grade 5 event (respiratory failure). Conclusions: Catequentinib hydrochloride demonstrated meaningful antitumor activity and durable responses in adults with advanced ASPS. Despite the ORR of 26.8% slightly below the predefined 31% threshold, disease control was prolonged, with a m-DOR exceeding 22 months. Favorable PFS and OS outcomes, together with a manageable safety profile, support its clinical benefit in this ultra-rare sarcoma. Clinical trial information: NCT03016819 .

11177 Background: Early detection of recurrence after curative-intent treatment is a critical priority, traditional imaging often detects relapse when disease burden is high, potentially limiting treatment efficacy. ctDNA has emerged as an established prognostic biomarker for molecular residual disease (MRD) detection and early relapse. We performed a real-world meta-analysis on published datasets that utilized personalized, tumor-informed ctDNA testing to assess its performance across tumor types and clinical management approaches. Methods: Real-world studies published from December 2022 to December 2025 using the personalized, tumor-informed Signatera ctDNA assay (Natera, Inc.) were included. Eligibility required ctDNA assessment in the MRD (2–16 weeks post-surgery (histology dependent)/pre adjuvant therapy (ACT)) and/or surveillance (post-ACT/end of the MRD window if no ACT was given) settings, with outcomes stratified by ctDNA status and hazard ratios (HR) reported from univariable or time-dependent Cox regression analysis. Exclusions included: clinical trials, biobanks, metastatic disease treated with palliative intent, case reports, reviews, editorials, or commentaries. Clinical outcomes were harmonized into a composite event-free survival (EFS) endpoint (time to recurrence, progression, or death). Pooled HRs and 95% CIs were estimated using random and fixed effects models and heterogeneity between studies was assessed using the I 2 and Cochran’s Q test. Median lead time from ctDNA-positivity to radiographic or clinical recurrence was summarized when available. Results: We identified 18 eligible publications comprising 3,004 unique patients across 15 solid tumor types. During the MRD window, ctDNA positivity was associated with a significantly increased risk of an EFS event compared with ctDNA negativity (pooled HR: 8.15; 95% CI: 6.12–10.85, I 2 = 0.00%, P = 0.844, n = 13). During the surveillance window, inclusive of post-definitive treatment, ctDNA positivity conferred an even greater EFS risk (pooled HR: 18.30; 95% CI: 14.17–23.65, I 2 = 0%, P = 0.911 for heterogeneity, n = 16). Across studies, ctDNA detection during surveillance preceded radiographic or clinical recurrence by a median of 3.20 months (95% CI: 2.50-4.10, P < 0.0001, n = 10), although this varied substantially by study/tumor type (I 2 = 80.9%). Conclusions: In this pan-cancer real-world meta-analysis, ctDNA positivity assessed using a tumor-informed assay was highly prognostic following curative-intent therapy at all timepoints evaluated with low heterogeneity between studies. These findings support the broad clinical utility of tumor-informed ctDNA testing for post-treatment risk stratification and longitudinal disease monitoring across solid tumors.