ScVital Integration of Human normal Lung and LUAD scRNA-seq data

Determining overlapping genes for UPS GEMM and 2 PDXs with scVital and with the normal workflow

Heatmaps of expression of 29 key gene signatures in (A) SARC028 and (B) Stanford RNA sequencing data

e23566 Background: Advanced undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLS) are difficult to treat soft tissue sarcomas with response rates to first line systemic therapy between 10-30%. However, both UPS and DDLPS have been shown to have measurable tumor infiltrating lymphocyte (TIL) populations. LN-144 (lifileucel), an autologous TIL product derived from unresectable or metastatic melanoma, was shown to have an overall response rate (ORR) of 36% in heavily pretreated melanoma patients with a median DOR of 19.7 months. We hypothesized that generation and infusion of LN-145, an autologous TIL product from non-melanoma solid tumors, in this case UPS and DDLPS, would be both safe and feasible. Methods: NCT05607095 is a single center multi-cohort pilot trial with Cohort 2 enrolling patients with metastatic or unresectable UPS or DDLS to undergo autologous TIL therapy with LN-145. Eligible patients had to receive at least 1 prior line of systemic therapy, a lesion at least 1.5 cm in size available for TIL harvest, and adequate organ function and performance status (ECOG 0-1). After surgical excision of suitable tumor for TIL expansion, successful LN-145 product generation was determined by characteristics that meet pre-specified criteria in the LN-145 IND. Patients then underwent nonmyeloablative lymphodepletion with cyclophosphamide (60 mg/kg x 2 doses) and fludarabine (25 mg/m 2 x 5 doses). LN-145 was then infused and expanded with intravenous interleukin 2 (600,000 IU/kg up to 6 doses). Primary endpoints of the trial were feasibility, defined as ³6 of 10 harvested pts undergoing LN-145 therapy, and safety, defined by the incidence of Grade ³3 adverse events (AE) as measured by CTCAE v5.0. Key secondary endpoints included estimated LN-145 manufacture rates and efficacy (ORR) utilizing RECIST 1.1. Exploratory endpoints include persistence of LN-145 cells and immune correlates in tissue and peripheral blood and their potential association with objective response and toxicity. Safety and efficacy measures will be summarized using point estimates and a Clopper Pearson exact confidence interval will be used. The final results of the primary feasibility and safety endpoints and secondary feasibility endpoint for the first 10 enrolled patients as well as and preliminary secondary efficacy and exploratory correlative studies through week 12 for 7 treated patients will be reported as late-breaking abstract after data lock on March 1, 2026. Clinical trial information: NCT05607095 .

11500 Background: GIST, the most common mesenchymal malignancy of the gastrointestinal tract, is commonly driven by activating KIT mutations. Despite therapeutic advances, treating advanced GIST with KIT tyrosine kinase inhibitors (TKIs) remains challenging due to emergence of heterogeneous resistance mutations inadequately addressed by current approved therapies. Bezuclastinib, an oral, selective type 1 TKI, in combination with sunitinib, a type 2 TKI, inhibits common primary and secondary resistance mutations in advanced KIT -mutant GIST. The Peak study evaluated efficacy and safety of bezuclastinib + sunitinib vs standard second-line sunitinib monotherapy in patients with advanced GIST who received prior imatinib therapy. Methods: Peak was a multipart study: dose confirmation (Part 1a), 2 drug-drug interaction (DDI) assessments (Part 1b; DDI substudy), and a randomized phase 3 (Part 2; abstract focus). Patients were randomized 1:1 to bezuclastinib 600 mg once daily (QD) + sunitinib 37.5 mg QD (n=204) or sunitinib 37.5 mg QD (n=209). Primary endpoint was blinded independent central review (BICR)-assessed median progression-free survival (mPFS). Key secondary endpoints were objective response rate (ORR) per BICR and overall survival (OS). Crossover to combination was permitted at BICR-confirmed progression. Results: Patients (N=413) were randomized to either bezuclastinib + sunitinib or sunitinib monotherapy; median (range) age, 63 (30-88) years; 59.6% and 14.0% had activating KIT mutations in exons 11 only and 9 only, respectively. The combination significantly improved mPFS (HR, 0.50; 95% CI, 0.39-0.65; P<0.0001). mPFS was 16.5 months (95% CI, 13.8-19.2) for the combination vs 9.2 months (95% CI, 7.2-11.0) for monotherapy. ORR significantly improved with the combination vs monotherapy (46% vs 26%; risk difference, 20%; 95% CI, 10.6-28.6; P<0.0001). As of Sep 30, 2025, OS data remain immature. Incidence of adverse events (AEs) was similar between arms. Grade (Gr)≥3 AEs were comparable, with no significant increase in common sunitinib-associated AEs. Higher rates of Gr≥3 ALT/AST elevations and anemia were observed with the combination and were manageable with dose modification. ALT/AST elevations led to bezuclastinib dose reductions in 13.2% and discontinuations in 1.5% of patients in the combination arm; all Gr3 hepatic AEs resolved; no Gr4 events occurred. Additional treatment-emergent AEs leading to discontinuation of either drug in >1 patient in the combination arm were neutropenia (2.9%) and diarrhea (1%). No treatment-related AEs led to death in the combination arm. Conclusions: Combined KIT inhibition with bezuclastinib + sunitinib significantly improved mPFS vs sunitinib monotherapy, reducing the risk of progression or death by 50% and increasing ORR from 26% to 46%. The combination was well tolerated with no new safety findings. Clinical trial information: NCT05208047 .

11553 Background: Immune checkpoint inhibitors (ICIs) are an established treatment for many malignancies, with an emerging role in sarcoma. While the impact of concomitant medications (CM) on ICIs has been described in other cancers, it has not been evaluated in sarcoma. We assessed the association between CM use and ICIs outcomes in sarcoma patients. Methods: This pooled post hoc analysis included 7 investigator-initiated phase II ICI-based trials enrolling patients with metastatic sarcoma between April 1, 2017, and May 30, 2024. Patients receiving ≥1 dose of ICIs were included. CM taken within 30 days prior to treatment initiation were defined as baseline; PRN medications were excluded. CM were recorded at each cycle through end of treatment and categorized by medication class; supplements/herbal agents included vitamins, minerals, probiotics, botanicals, amino acids, and other dietary substances. For progression-free survival (PFS), baseline and on-treatment CM were analyzed as time-dependent covariates using Cox proportional hazards models. Overall survival (OS) analyses were limited to baseline CM. Logistic regression evaluated associations between baseline CM and objective response (ORR) and immune-related adverse events (irAEs). Toxicity was graded per CTCAE v5.0. Results: A total of 321 patients (median age, 58 years) were included. The most common histologies were liposarcoma (all subtypes, 22%), undifferentiated pleomorphic sarcoma (22%), and leiomyosarcoma (19%); 46% had received ≥3 prior lines of therapy. ICI was combined with cytokine/oncolytic therapies (43%), targeted agents (38%), or chemotherapy (19%). After a median follow-up of 47.4 months, ORR was 18%, median PFS was 3.9 months (95% CI, 3.09–5.32), and median OS was 19.9 months (95% CI, 17.5–22.9). Grade ≥3 irAEs occurred in 25% of patients, most commonly hematologic (6%) and hepatic (5%). On-treatment use of supplements/herbal agents was associated with longer PFS (HR 0.64, 95% CI 0.50–0.82; p<0.01), while on-treatment anti-infective use was associated with shorter PFS (HR 1.55, 95% CI 1.06–2.25; p=0.02); baseline anti-infective use was not associated with PFS. Baseline supplement/herbal use was associated with longer OS (HR 0.69, 95% CI 0.53–0.90; p<0.01), whereas baseline non-opioid (HR 1.54, 95% CI 1.10–2.16; p=0.01) and opioid analgesic use (HR 2.14, 95% CI 1.45–3.14; p<0.01) were associated with shorter OS. Baseline antihistamine use showed a trend toward increased gastrointestinal irAEs (OR 2.37, 95% CI 0.97–5.98; p=0.06). No CM class was associated with ORR. Conclusions: Concomitant medication use is associated with differential ICI outcomes in metastatic sarcoma and warrants prospective evaluation. CM Timing Outcome HR SH OT PFS 0.64 AI OT PFS 1.55 AI BL PFS 1.37* SH BL OS 0.69 Non-OA BL OS 1.54 OA BL OS 2.14 *Not statistically significant; SH = Supplements/herbal agents, AI = Anti-infectives, OA = Opioid analgesia, OT = on-treatment, BL = Baseline.

TPS11598 Background: Fibroblast Activation Protein (FAP) is expressed on the surface of cancer-associated fibroblasts and is involved in the formation, maintenance, and spread of tumors. Sarcoma frequently demonstrates high expression of FAP on the tumor cells themselves in contrast to other solid tumors, where it is mainly expressed on CAFs within the tumor stroma. Radioligand therapies utilizing alpha emitting isotopes such as Ac-225 have emerged as promising treatment strategies across multiple targets and indications in oncology. Ac-225 and its daughter radionuclides emit high-energy alpha particles capable of inducing double-stranded DNA breaks, leading to significant cytotoxic effects within cells. Early clinical data for other Ac-225-labeled compounds have shown promising outcomes, particularly in settings where traditional therapies have failed. [Ac-225] RTX-2358 (Ratio Therapeutics Inc, Boston, MA) is a novel FAP-targeted radioligand designed for specific high-affinity binding, resulting in prolonged tumor residence and limited normal tissue uptake. This sustained tumor retention leads to extended delivery of cytotoxic radiation to FAP-expressing tumors. A beta-emitting analog, [Lu-177]RTX-2358, has been administered to more than 25 patients under the German §13.2b compassionate use framework across multiple tumor types. Longitudinal SPECT imaging performed as late as 14 days after administration demonstrated persistent tumor retention with minimal washout. Based on time–activity curve analysis from these data, tumor biological half-time is estimated to be well in excess of 1,000 hours. Renal clearance was observed to be consistent with that reported for established lutetium-177–labeled radioligand therapies. Methods: This study is a seamless Phase 1 / 2 dose escalation study. The Phase 1 portion consists of a 3 x 3 dose escalation design, with patients treated in 3 planned dose escalation cohorts (7.5, 11.25 and 15 MBq) with up to 6, 8-week cycles of [Ac-225]RTX-2358. Backfill of phase 1 cohorts is permitted to facilitate selection of the recommended administered activity level for the subsequent Phase 2 expansion cohort. Dose escalation / de-escalation decisions will be made by a Safety Review Committee. Patients over 18yrs with a history of histologically confirmed relapsed or refractory soft tissue sarcoma (measurable disease per RECIST v1.1) are eligible if they have a positive [Cu-64]LNTH-1363S FAP PET, an ECOG PS 0 to 1, and adequate organ reserve and renal function. Recruitment of the first cohort was completed in December 2025. The ATLAS Study: NCT07156565 Clinical trial information: NCT07156565 .

ABSTRACT Background Concomitant medications (CMs) influence outcomes in patients receiving immune checkpoint inhibitors (ICIs), but their impact in sarcoma remains undefined. We assessed the association between CM use and ICI outcomes in patients with advanced or metastatic sarcoma. Methods This pooled analysis included patients from seven investigator‐initiated phase II trials of ICI‐based therapy for sarcoma. CMs within 30 days of treatment were defined as baseline; on‐treatment exposure was captured longitudinally. The primary endpoint was progression‐free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and immune‐related adverse events (irAEs). Multivariable Cox models adjusted for age, ECOG performance status, histological subtype, treatment regimen, and race. Results Among 321 patients (median follow‐up: 47.4 months), in time‐dependent analyses, exposure to anti‐infective medications was associated with shorter PFS (adjusted hazard ratio [aHR] 1.54, 95% CI 1.05–2.27). Baseline use of vitamins/minerals/supplements/herbal products was associated with longer PFS (aHR 0.73, 95% CI 0.56–0.95) and OS (aHR 0.67, 95% CI 0.51–0.89). Baseline statin use was associated with longer PFS (aHR 0.64, 95% CI 0.47–0.87) but not OS. Baseline use of opioids was associated with shorter OS (aHR 1.71, 95% CI 1.12–2.61). No CM class was significantly associated with ORR or irAE occurrence. Conclusions CM use is associated with differential efficacy outcomes in sarcoma patients receiving ICIs. These findings highlight the need for prospective studies to define the impact of commonly prescribed medications on ICI outcomes and to optimize clinical trial stratification.

Purpose: Pain management remains challenging for adolescent and young adult (AYA) cancer patients. Acupuncture and massage have been recommended for cancer-related pain management, but no prospective trials have been conducted in AYA patients. We explored the effects of acupuncture and massage on pain in AYAs. Methods: This subgroup analysis focused on AYA patients (aged 18-39 years) enrolled in a randomized controlled trial comparing acupuncture and massage for pain management in advanced cancer. Interventions were delivered weekly for 10 weeks, followed by monthly booster treatments through week 26. The primary outcome was the worst pain score from the Brief Pain Inventory, analyzed using a linear mixed-effects model. Results: Thirty participants met eligibility criteria (13 acupuncture; 17 massage), with a mean age of 31.1 years (standard deviation, 5.8); 57% were female; 67% were White; and 53% had solid tumors. Both groups experienced reduced pain over time. Relative to baseline, patients receiving acupuncture had a mean change of -1.26 points (95% confidence interval [CI], -2.54 to 0.01) at 10 weeks and a mean change of -1.46 points (95% CI, -2.78 to -0.14) at 26 weeks. Patients receiving massage experienced a mean change of -2.81 points (95% CI, -3.92 to -1.70) at week 10 and a mean change of -3.79 points (95% CI, -4.85 to -2.73) at week 26. Conclusion: AYA patients with advanced cancer who received either acupuncture or massage experienced clinically meaningful and sustained reductions in pain. These findings provide a promising foundation for future trials aimed at evaluating integrative pain management strategies in AYAs.

TPS11594 Background: Dedifferentiated liposarcoma (DDLPS) is a rare adipocytic malignancy characterized by frequent amplification of MDM2 and CDK4 and associated with poor outcomes, with a median overall survival of approximately 15 months. A phase II trial at Memorial Sloan Kettering Cancer Center demonstrated activity of the CDK4/6 inhibitor palbociclib in advanced WD/DDLPS, with a 12-week progression-free survival (PFS) rate of 57%, exceeding historical chemotherapy benchmarks (<35%) and leading to its inclusion in the NCCN Guidelines. Despite this, durability of benefit remains limited, and outcomes following progression are poor. Preclinical work from our group demonstrated that CDK4/6 inhibition in DDLPS induces cellular geroconversion from quiescence to irreversible senescence, accompanied by MDM2 downregulation. This process requires suppression of HRAS signaling and inhibition of the MAPK pathway and is associated with activation of the senescence-associated secretory phenotype (SASP). Preclinical models further suggest that dual CDK4/6 and MEK inhibition enhances SASP activation, providing a mechanistic rationale for combination therapy. Based on these findings, we initiated a phase Ib/II clinical trial of mirdametinib, a MEK1/2 inhibitor, in combination with palbociclib in patients with DDLPS (NCT06843967). Methods: This is an ongoing phase Ib/II, single-arm, open-label, single-center study evaluating the safety, tolerability, and efficacy of mirdametinib plus palbociclib in patients with unresectable, recurrent, or metastatic DDLPS (NCT06843967). Patients may enroll at any line of therapy, including first line, consistent with contemporary palbociclib use; patients with prior CDK4/6 inhibitor exposure are eligible for the phase Ib portion. Key eligibility criteria include ECOG performance status 0–2 and RECIST v1.1–measurable disease. Phase Ib uses a Bayesian optimal interval (BOIN) design with three dose levels to determine dose-limiting toxicities, maximum tolerated dose, and recommended phase II dose (RP2D), enrolling up to 24 patients. Phase II will assess efficacy at the RP2D, with the primary endpoint of PFS at 18 weeks by RECIST v1.1 in 30 patients. Enrollment began February 19, 2025. As of January 2026, accrual is ongoing at dose level 2. Enrollment to dose level 3 is anticipated in February 2026. Clinical trial information: NCT06843967 .

Histologic distribution by immunotype and response

BACKGROUND:Aggressive angiomyxoma (AA) is a rare, locally infiltrative mesenchymal tumor with frequent local recurrence. Optimal management remains poorly defined, particularly the roles of surgery, endocrine therapy, and observation. METHODS:We retrospectively analyzed patients with histologically confirmed AA treated at a single institution from 2000 to 2024. Clinical, pathologic, and treatment data were collected. Overall survival (OS), relapse-free survival (RFS), duration of treatment (DOT), and radiographic response by quasi-RECIST 1.1 were assessed descriptively. RESULTS:Forty patients were included; median age was 42 years, 87.5% were female, and median tumor size was 9.9 cm. Initial management was surgery in 30 patients, systemic therapy in 8, and observation in 2. Among patients initially managed with surgery, median OS from the time of first resection was not reached at a median follow-up of 68.6 months; estimated 10-year OS was 95% (95% CI, 68%-99%). Among patients with R0/R1 resection, median RFS was 49.8 months (95% CI, 21.0-64.7), with 3-year RFS of 56% (95% CI, 31%-75%). Tumor size and margin status were not significantly associated with recurrence. Thirteen patients received systemic therapy, predominantly endocrine-based; ORR was 25% and median DOT was 15.4 months. Two patients were initially observed, and three with residual macroscopic disease after R2 resection remained free from further intervention for prolonged periods. Radiation therapy was rarely used. CONCLUSIONS:AA was associated with excellent long-term survival despite frequent recurrence or subsequent intervention after surgery. Endocrine therapy showed objective activity in a subset of patients. Observation or delayed intervention may be feasible in selected, clinically stable patients with untreated or residual macroscopic disease, supporting individualized, function-preserving management focused on symptoms, morbidity, and patient preferences.

ScVital Integration of Normal Mouse and Human Lung scRNA-seq data

T cell subpopulations associated with shorter survival after accounting for histologic subtype and treatment

ScVital Integration of Normal Mouse and Human Pancreas scRNA-seq data

Comparison of integration clusters to scVital

2661 Background: CRD3874-SI is a first in class, systemically administered, allosteric STING agonist that blocks STING’s proton channel activity differentiating it from previously developed STING agonists. The drug has demonstrated pre-clinical anti-cancer activity in several murine tumor models and has pharmacological properties distinct from earlier generation STING agonists. Methods: This is a single institution, open-label, phase I study of CRD3874-SI in patients with advanced solid tumors. The dose escalation study follows a standard 3+3 design. CRD3874-SI is administered intravenously once per week for 2 cycles. Cycle duration is 28 days. From cycle 3 onwards, continuous weekly treatment +/- one week break (week 4) may be considered. The primary objective is to assess the safety of CRD3874-SI by determining the maximum tolerated dose, recommended phase 2 dose and schedule of administration. Secondary objectives include examining the pharmacokinetics and pharmacodynamics (IP10 analysis) of CRD3874-SI and evaluating the efficacy of CRD3874-SI as determined by best objective response rate per RECIST v 1.1. Clinical trial information: NCT06021626. Research sponsor: Curadev Pharma, Inc. Results: As of January 5th 2026, 21 patients (sarcoma n=20, adenoid cystic carcinoma n=1) received treatment at four escalating dose levels (0.1-1.8mg/kg). The median number of prior lines of treatment was 4 (1-11). The median duration of treatment was 7 weeks (range: 1-32 weeks). 2 patients continue treatment. Reasons for treatment discontinuation include: progression of disease (n=16), toxicity (n=2), patient withdrawal (n=1). Treatment emergent adverse events (TEAEs) were manageable and reversible. Only low-grade cytokine related symptoms were reported. TEAEs possibly related to study treatment reported in >20% of participants and were mostly low grade include: fatigue (43%), chills (38%), nausea (38%), diarrhea (33% (G3 (10%)), headache (29%) and flu-like symptoms (24%). Low grade colitis not typical of auto-immune mechanism, responding well to temporary treatment pause +/- oral budesonide, were reported in 4 patients. One DLT at dose level 4 (G3 dyspnea) was observed. 19 patients are evaluable for efficacy. The best objective response per RECIST v1.1: confirmed partial response, n=1 (malignant phyllodes tumor); stable disease, n=9; progressive disease, n=9. Dose level 3 (0.9mg/kg) represents a biologically active dose (one confirmed PR and a second case with -27% tumor regression was observed). Dose proportional increase in AUC with concomitant increase in plasma CXCL10 levels were observed. Conclusions: CRD-3874-SI has demonstrated clinical activity with manageable safety. Dose level 0.9mg/kg is biologically and clinically active. A dose expansion phase at this dose level in is planned in >5 histology specific cohorts. Clinical trial information: NCT06021626 .

Detailed histologic diagnoses according to TME subtype

Abstract Introduction: Identifying novel approaches that harness and augment anti-tumor immune response is an important area of ongoing research and drug development. Based on their performance in pre-clinical models, orthosteric activators of the Stimulator of Interferon Genes (STING) have been investigated in human trials. The activation of STING by its ligand cGAMP leads to both IFN dependent innate immune signaling as well as IFN independent pharmacology associated with STING's proton transport activity that leads to autophagy and pyroptosis. CRD3874 is a first in class small molecule allosteric STING agonist that binds to an allosteric site within STING's proton channel and decouples the IFN and non-IFN consequences of STING activation by blocking STING's non-IFN actions. CRD3874-SI, is a proprietary intravenous formulation of CRD3874, potent activator of all five human STING variants that has demonstrated promising pre-clinical anti-cancer activity in serval mouse tumor models when systemically administered as mono therapy or in combination with checkpoint therapy. Drug administration led to elevated plasma levels of CXCL10 and IFNβ in mice and monkeys. High IV doses up to 75mg/kg were systemically tolerated in cynomolgus monkeys. Methods: This is a single institution, phase Ia/b study of CRD3874-SI in patients with advanced solid tumors who received at least one line of prior therapy. The dose escalation phase will explore the safety and tolerability of CRD3874-SI following standard 3+3 design. CRD3874-SI is administered by intravenous infusion once per week for two cycles. From cycle 3 onwards, participants will received 3 or 4 consecutive weekly infusions, over a 28-day treatment cycle. The primary objective is to assess the safety and tolerability of CRD3874-SI by determining the maximum tolerated dose, recommended phase 2 dose and schedule of administration. Secondary objectives include further defining the safety profile, examining the pharmacokinetics and pharmacodynamics (CXCL10 analysis) of CRD3874-SI and evaluating the efficacy of CRD3874-SI as determined by the best objective response rate and clinical benefit rate per RECIST v1.1. Treatment will continue until disease progression or unacceptable toxicity. This study is currently open to enrollment. 21 patients have received treatment across 4 dose levels to date. Expansion cohorts are planned after determining the appropriate dose (RP2D). Clinical trial information: NCT 06021626. Research sponsor: Curadev Pharma, Inc. Citation Format: Ciara M. Kelly, Reinhard von Roemeling, Monali Banerjee, Viswatej Avutu, Olayade Babatunde, Lauren Banks, Ping Chi, Mark A. Dickson, Mrinal M. Gounder, Grace Gray, Camron Clark, Mary Louise Keohan, Robert G. Maki, Sujana Movva, Damon Reed, Kelly Schroeder, Li-Xuan Qin, Phillip Wong, Sandip Middya, Ritesh Shrivastava, Debjani Chakraborty, Rajib Ghosh, Sourav Basu, Arjun Surya, William D. Tap, Sandra P. D'Angelo. Phase I trial of CRD3874-SI, a systemically administered third generation allosteric STING agonist, in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT295.