Citations

e19046 Background: While outcomes in pts with R/R FL have improved with current SOC treatments (Tx), there remains a need for safe, efficacious, and convenient Tx options. GOLCA is a potential, first-in-class, oral CELMoD designed for Tx of lymphoma, with preferential distribution to lymphoid organs and enhanced activity in lymphoma cell lines. GOLCA induces rapid and deep degradation of Ikaros and Aiolos, leading to direct cell killing and immunomodulatory activity. GOLCA + R was well tolerated and effective in heavily pretreated pts in the two-part Ph 1/2 study, CC-99282-NHL-001. Here, we provide longer f/u in pts with R/R FL from Part B of the study. Methods: Pts with R/R FL with ≥2 prior lines of Tx (≥1 if prior anti-CD20 Tx) received GOLCA orally, once daily at 0.2 mg (n=22) or 0.4 mg (n=38) ± R for up to 2 y or until progressive disease (PD)/unacceptable toxicity. Primary endpoints included safety and RP2D determination; secondary endpoints are preliminary efficacy and PK. Results: As of September 15, 2025, 60 pts were enrolled. In 0.2 and 0.4 mg groups, median prior Tx lines were 3 and 3, 32% and 32% had prior lenalidomide (LEN), 27% and 29% had prior T-cell–redirecting Tx (CAR T and/or bispecific antibody) and 32% and 32% were refractory to last regimen. Tx is ongoing in 6 (27%) and 17 (45%) pts at 0.2 and 0.4 mg, respectively; discontinuations (d/c) were mostly due to PD. Neutropenia, an on-target side effect of GOLCA, was the most common grade 3/4 Tx-emergent adverse event (TEAE) occurring in 59% and 68% of pts at 0.2 and 0.4 mg, followed by anemia (9% and 16%) and febrile neutropenia (9% and 8%). Median time to resolution of neutropenia was 8 days. Dose reductions occurred in 14% and 37% of pts at 0.2 and 0.4 mg, most commonly due to neutropenia (5% and 21%) and febrile neutropenia (5% and 5%). No d/c or deaths were from GOLCA-related TEAEs. Non-hematologic TEAEs were infrequent and mostly low grade. In efficacy-evaluable pts (GOLCA 0.2 and 0.4 mg + R, n=22 and n=36), median f/u was 14.03 months (mo), overall response rate (ORR) was 77% (complete response rate [CRR], 41%) at 0.2 mg, and 97% (CRR, 78%) at 0.4 mg. In the 0.4 mg group, responses were consistent in high-risk subsets including pts with prior LEN (ORR, 100%; CRR, 75%) and/or T-cell–redirecting Tx (ORR, 91%; CRR, 64%). GOLCA 0.4 mg + R demonstrated durable responses (median DOR, 9.17 mo; 91% of pts who achieved a CR remained in CR at cutoff). Conclusions: With longer f/u, GOLCA + R demonstrated promising efficacy with durable responses and no new safety signals. The 0.4 mg group had higher ORR and CRR than 0.2 mg, including in pts with prior LEN-based and/or T-cell–redirecting Tx, with a manageable safety profile at both doses. The results support the development of GOLCA + R as a fixed-duration, chemotherapy-free outpatient Tx in the Ph 3 GOLSEEK-4 study in 2L+ FL (NCT06911502). Clinical trial information: NCT03930953 .

e16304 Background: Hepatic reserve is a critical determinant of outcomes in hepatocellular carcinoma (HCC), yet traditional scoring systems such as MELD are frequently unavailable or underpowered in real-world datasets. The albumin–bilirubin index (ALBI) is a validated, objective measure of liver function derived from routine laboratory values and has emerged as a pragmatic alternative for risk stratification. However, the impact of ALBI on longitudinal outcomes following locoregional therapy (LRT) for HCC in routine clinical practice remains incompletely characterized. Methods: We performed a retrospective cohort study using TriNetX to identify adults with HCC treated with locoregional therapies (transarterial chemoembolization, yttrium-90 radioembolization, stereotactic body radiation therapy, or thermal ablation). Hepatic reserve was assessed using an albumin–bilirubin–based definition with labs within 30 days pre-therapy. Low ALBI (preserved function) was defined as albumin ≥3.5 g/dL and bilirubin ≤2.0 mg/dL, and high ALBI (impaired function) as albumin < 3.5 g/dL or bilirubin > 2.0 mg/dL. Propensity score matching (1:1) balanced demographics and comorbidities. Outcomes at 6 months, 1, 3, and 5 years included mortality, hepatic failure, ascites, portal hypertension, and esophageal varices. RD, RR, OR, and HR with 95% CIs were reported. Results: After matching, 509 patients were included in each ALBI group. High ALBI was consistently associated with significantly worse outcomes across all time points. Overall mortality was higher in the high-ALBI group at 6 months (19.6% vs 8.7%), 1 year (31.0% vs 13.9%), 3 years (51.0% vs 28.3%), and 5 years (57.1% vs 35.6%). Corresponding hazard ratios for mortality ranged from 2.32 to 2.65 across time points (all p < 0.05). High ALBI was also associated with substantially increased risks of hepatic failure (5-year RD 23.9%, HR 3.29), ascites (5-year RD 18.5%, HR 2.50), and esophageal varices (5-year RD 8.5%, HR 2.60). These associations persisted from early through long-term follow-up, demonstrating durable prognostic separation by ALBI status. Conclusions: In this large, real-world cohort of HCC patients undergoing locoregional therapy, impaired hepatic reserve as defined by a high albumin–bilirubin index was strongly and consistently associated with worse short- and long-term survival and higher rates of hepatic decompensation. An albumin–bilirubin–based ALBI classification represents a pragmatic and clinically meaningful tool for risk stratification when MELD is unavailable and may inform treatment selection, prognostication, and post-therapy surveillance in routine clinical practice.

e14545 Background: Durable antitumor immunity depends on the maintenance of stem-like CD8⁺ T cells capable of sustaining long-term effector responses. Oncolytic viruses (OVs) are potent immunomodulatory agents that reshape the tumor microenvironment and augment antitumor immunity. We hypothesized that platinum-based chemotherapy alters tumor-intrinsic type I interferon (IFN-I) signaling in a manner that can be functionally restored by OV therapy, thereby promoting the generation and persistence of stem-like CD8⁺ T cells. Methods: Tumor cells treated with platinum chemotherapy were evaluated in vitro for changes in IFN-I pathway activity, OV replication, and markers of immunogenic cell death (ICD). Syngeneic mouse tumor models were used to assess antitumor efficacy and immune remodeling following combination therapy. Tumor-infiltrating lymphocytes were analyzed by single-cell RNA sequencing and multiparameter flow cytometry to define CD8⁺ T-cell states and functional programs. Guided by these preclinical findings, a clinical trial combining XELOX, PD-1 blockade, and OV therapy was initiated (ChiCTR2500107607). Results: Platinum chemotherapy significantly suppressed tumor-intrinsic IFN-I signaling, while OV therapy restored antiviral responses, enhanced viral replication, and increased ICD in vitro. In vivo, the combination strategy resulted in superior tumor control and profound remodeling of the tumor immune microenvironment. The most pronounced immunologic effect was observed within the stem-like CD8⁺ T-cell compartment. Combination therapy induced a distinct population of TCF7⁺ ISG15^high NFATC1^low AP-1^low CD8⁺ T cells, characterized by restrained activation, enhanced persistence, and reduced propensity toward terminal exhaustion. In IRF7-deficient tumors, this stem-like CD8⁺ T-cell population failed to emerge and antitumor efficacy was significantly diminished, indicating that moderate tumor-intrinsic IFN-I signaling is required for this immune state. Conclusions: Tumor-intrinsic type I interferon signaling is a critical determinant of synergy between platinum chemotherapy and oncolytic virotherapy, enabling the maintenance of durable stem-like CD8⁺ T-cell immunity. These findings establish a mechanistic rationale for combining platinum chemotherapy, oncolytic viruses, and immune checkpoint blockade and support ongoing clinical translation. Clinical trial information: ChiCTR2500107607.

e12707 Background: Anthracycline-based chemotherapy remains a cornerstone of breast cancer treatment but is limited by dose-dependent cardiotoxicity. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardioprotective effects across diverse populations. Preclinical models suggest they may mitigate anthracycline-induced cardiotoxicity. However, clinical data evaluating this association remain limited. Methods: We conducted a retrospective cohort study using the TriNetX real world data platform, including adults with breast cancer who received anthracycline within one year of diagnosis. Patients were stratified by SGLT2i use within one year of diagnosis into the SGLT2i group and the non-SGLT2i group. Propensity score matching (PSM) was performed to balance baseline demographics and comorbidities. Outcomes included 3-year all-cause mortality, heart failure, myocardial infarction, atrial fibrillation, mean left ventricular ejection fraction (LVEF), mean Troponin I, and mean brain natriuretic peptide level (BNP), analyzed using risk ratios (RR) and Kaplan-Meier survival analysis. Results: After PSM, 2912 patients were included in each group, with a mean follow-up of 630.3 days in SGLT2i group and 756.7 days in non-SGLT2i group. Mean age was 61.5 years vs 62.3 years (SGLT2i group vs non-SGLT2i group), with more than 98% of females in both groups. Most patients were White (49.0% in SGLT2i group and 48.6% in non-SGLT2i group), followed by African American (23.7% vs. 23.4%), unknown races (14.0% vs 14.0%), and Asian (9.5% vs. 9.8%). At baseline, the SGLT2i group had lower mean LVEF (53.4% vs 61.9%), higher mean Troponin I (0.992 vs 0.0849), and higher mean BNP levels (778 vs 240). SGLT2i group was associated with significantly lower 3-year all-cause mortality (Hazard ratio 0.52, 95% CI 0.44–0.61). Heart failure incidence (9.5% vs 6.0%; p = 0.0005) was significantly higher in the SGLT2i group. Mean LVEF in SGLT2i group was significantly lower (51.7% vs 58.9; p < 0.0001) and mean BNP level was significantly higher in SGLT2i group (685.5 vs 383.0; p = 0.0336). No significant differences were observed in myocardial infarction (3.9% vs 3.4%; p = 0.4459), atrial fibrillation (3.4% vs 4.5%; p = 0.0799), and mean troponin I (0.085 vs 0.113, p = 0.5191). Conclusions: In this real-world cohort, SGLT2i use was associated with lower 3-year all-cause mortality despite higher rates of heart failure. Notably, patients receiving SGLT2i had worse baseline cardiac function yet demonstrated more favorable trends in cardiac biomarkers, including smaller declines in LVEF, reductions in BNP, and lower mean troponin I levels, suggesting a slower progression of cardiac dysfunction. These findings support a potential cardioprotective and survival benefit of SGLT2i in patients with breast cancer receiving anthracycline therapy and warrant confirmation in future studies.

9567 Background: Resected stage IIB/C and microscopic stage IIIA/B/C/D melanoma presents a significant risk of recurrence risk of 37 to 62% at 5 years (yrs). While 1 year of adjuvant PD1 therapy reduces this risk by approximately half, the individual patient’s baseline risk without treatment and their specific benefit from adjuvant PD1 remain unknown. We aimed to generate two separate predictive models for recurrence – one for untreated and one for treated pts - to calculate the individualised benefit of adjuvant PD1. Methods: Pts with resected stage IIB/C or microscopic stage IIIA/B/C/D melanoma, either treated with adjuvant PD1 or untreated at 13 major melanoma centres, and with at least 2 years of follow-up from surgery were included. We analysed pts demographics, disease characteristics, blood parameters, pathological and imaging data at baseline, and clinical outcomes. Propensity scores were estimated using logistic regression with covariates associated with treatment in univariate screening (p<0.05). Separate penalised multivariable logistic regression models were built to predict recurrence for treated and untreated pts. A tool based on these models was created to calculate the individual patient benefit from adjuvant PD1. Results: A total of 3560 pts was included, divided into untreated (discovery n=2384 and validation n=597) and treated (discovery n=404 and validation n=175) cohorts. The model for untreated pts included age, gender, primary site, histological subtype, Breslow thickness, ulceration, mitosis, number and site of regional lymph nodes (LN), mutation status and LDH (AUC 0.70 in discovery, 0.69 in validation). The model for treated pts included age, gender, Breslow thickness, site of regional LN, and mutation status (AUC 0.69 in discovery, 0.61 in validation). ADAPT-M (ADjuvant Anti-PD-1 Tool for Melanoma) calculates the individualized benefit of adjuvant PD1. For example, patient A, a woman ≤45 years old with a primary head & neck melanoma (superficial spreading, thickness >1-2 mm, no ulceration, 1 mitosis/mm 2 ), 2 clinically occult LN metastases in the neck, NRAS mutant, and normal LDH, has a 12-month recurrence risk of 21.9% untreated vs 2.3% treated (benefit 19.6%), and a 24-month risk of 41.1% untreated vs 6.4% treated (benefit 34.7%). While, patient B, a man ≤45 years old with a primary melanoma in the lower limb (nodular, thickness >1-2 mm, no ulceration, 1 mitosis/mm 2 ), 2 clinically occult LN metastases in the groin, BRAF V600 mutant, and normal LDH, has a 12-month recurrence risk of 14.2% untreated vs 11.8% treated (benefit 2.5%), and a 24-month risk of 28.0% untreated vs 30.1% treated (no benefit). Conclusions: ADAPT-M, a clinical tool that estimate individualized recurrence risks with and without adjuvant anti-PD1 therapy, quantifies the absolute benefit of treatment for pts with high-risk resected melanoma, facilitating personalized adjuvant therapy decisions.

9524 Background: Unresectable melanoma in-transit metastases (ITM) can pose a significant clinical challenge. Our recently published data comparing first-line treatments for ITM, isolated limb infusion or perfusion (ILI/ILP), immune checkpoint inhibitors (ICI) and intralesional talimogene laherparepvec (TVEC), found superior outcomes with TVEC. However, TVEC was used more often in patients with lower disease burden and earlier stage (IIIB vs. IIIC/D). Therefore, we sought to better investigate these differences with a propensity score-matched (PSM) analysis. Methods: A multi-institutional, international IRB- approved retrospective analysis was conducted for unresectable melanoma ITM from 2016-2022. PSM analysis comparing first-line ILI/ILP, ICI, and TVEC for was performed. Patients were matched for stage, number of ITM, anatomical site, CLND status, gender and age. Kaplan-Meier curves (OS, PFS, DMFS) and Cumulative incidence function (MSS) were used to visualize time-to-event outcomes in the PSM cohort, though both methods do not account for the matched structure. Results: 274 patients were identified, 120 female/154 male; 96 treated with ILI/ILP, 111 with ICI, and 67 with TVEC. Median follow-up was 40 months (range, 1-80). PSM was performed and identified 36 TVEC–ICI pairs and 27 TVEC–ILI pairs. These were combined resulting in a final cohort of 108 observations (45 TVEC, 36 ICI and 27 ILI). The groups were well balanced. No statistical difference was found for metastasis-free survival (DMFS), progression-free survival (PFS), melanoma-specific survival (MSS), and overall survival (OS) between treatment modalities. TVEC was associated with significant improvement in local PFS (median was 2.2 years (y) for ILI/ILP, 1.5y for ICI and not reached for TVEC, p=0.048). While not statistically significant, a clinical benefit was seen in PFS being longer for TVEC (2.1y for TVEC vs. 1.2y for ILI/ILP and 1.1y for ICI; p=0.2) and OS (not reached vs 2.9y for ILI/ILP and 5.2y for ICI; p=0.2). On mixed effect Cox regression proportional hazard model using the matched data set, there were no significant differences in any of the survival and recurrence outcomes. Conclusions: When patients are propensity-matched, there were no significant differences in first-line treatment modalities for unresectable melanoma ITM. Treatment with TVEC did result in clinically meaningful improved overall and local PFS and OS. This supports that selection of ITM therapy should incorporate an individualized approach, incorporating disease distribution, stage, burden, treatment side effects and patient priorities.

9535 Background: MUM carries a poor prognosis with few effective treatments, especially for HLA-A*02:01-negative pts. While a subset of MUM pts responds to immune checkpoint inhibitors, the comparative efficacy of IPI+PD1 versus PD1 monotherapy is unclear. This study compares objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety between these regimens in MUM. Methods: MUM pts treated with PD1 or IPI+PD1 at 15 major melanoma centres (from Australia, Europe, United States and Israel) were included. Demographics, patient and disease characteristics, and clinical outcomes were examined. Univariate and multivariate (MVA) analyses were performed to identify clinical predictors of response and survival. Results: Of 412 MUM pts treated, 150 (36%) had PD1 and 262 (64%) received PD1+IPI. Compared to the PD1 group, PD1+IPI-treated pts were younger (64 vs. 70 years; p<0.001), had higher rate of elevated LDH (44% vs. 31%; p=0.037), and more frequently had prior treatment with tebentafusp (6.5% vs. 1.3%; p=0.031). Median follow-up from commencement of PD1+/-IPI was 4.9 years (95% CI 4.7 – 6.1). ORR was higher in IPI+PD1 group (18%) vs. PD1 (9%) (p=0.008), particularly in males (p=0.009), patients with liver metastases (p=0.018) and with lung metastases (p=0.011), with elevated LDH (p=0.047) and with no prior treatment with tebentafusp (p=0.007). PFS and OS at 1 and 2 years were numerically higher with IPI+PD1 (1- and 2-year PFS: 23% and 15%; 1- and 2-year OS: 63% and 39%) vs. PD1 (1- and 2-year PFS: 17% and 11%; 1- and 2-year OS: 54% and 36%), but these differences were not statistically significant (p>0.05). On MVA, adjusting for predefined variables (age, gender, ECOG PS, LDH, presence/absence of liver/lung metastases, prior treatment with tebentafusp), IPI+PD1 was associated with higher ORR (OR 2.71, 1.30 – 6.05; p=0.01) but not with PFS or OS compared to PD1. Presence of liver metastases (ORR [OR 0.28; 95% CI 0.13 - 0.64], PFS [HR 1.61; 95% CI 1.11 - 2.34], OS [HR 2.02; 95% CI 1.32 - 3.10]), ECOG PS≥2 (PFS [HR 1.82; 95% CI 1.07 - 3.10], OS [HR 2.24; 95% CI 1.25-4.01]), elevated LDH (PFS [HR 1.66; 95% CI 1.30 - 2.11], OS [HR 2.39; 95% CI 1.84-3.10]) and prior tebentafusp treatment (OS [HR 2.36; 95% CI 1.21-4.59]) were also independent predictors of response and/or survival. A higher percentage of pts experienced grade ≥3 immune-related adverse events (irAEs) in the IPI+PD1 group compared to the PD1 group (34% vs 13%, p<0.0001). Most pts ceased treatment due to progression (234, 57%), and more pts stopped due to toxicity in the IPI+PD1 vs. PD1 group (25% vs. 9%, p<0.0001). Conclusions: In pts with MUM, IPI+PD1 demonstrated a higher ORR but did not improve survival compared with PD1 alone. IPI+PD1 was more toxic, leading to early treatment discontinuation in one-quarter of pts. These findings may help guide treatment selection in MUM.

7028 Background: Axi-cel, autologous anti-CD19 CAR T-cell therapy, showed long-term survival and curative potential in R/R LBCL (ZUMA-1; Neelapu et al. Blood . 2023). Few studies have examined long-term outcomes beyond clinical trials. Here we report long-term real-world outcomes of axi-cel in R/R LBCL using large-sample CIBMTR data. Methods: A total of 1500 adults from 79 US centers receiving commercial axi-cel after ≥2 LOT for LBCL from Oct 2017-Aug 2020 were enrolled in a post-marketing requirement study. A protocol was developed prior to the study’s implementation, reviewed by Kite and CIBMTR. This is a secondary analysis of said study. Key outcomes were progression-free survival (PFS), overall survival (OS), time to next therapy (TTNT), disease-specific mortality (competing risks were non-relapse deaths), subsequent malignancies, and non-relapse mortality (NRM). Outcomes were analyzed descriptively. Cases with missing data were excluded separately for each endpoint. Results: As of Aug 2025, 1446 patients (pts) were included in the analysis. Median age at infusion was 62.2 y (range, 19.6-90.8: 38% of pts ≥65 y); 65% were male. Five percent of pts had ECOG PS ≥2 and 16% had high-grade lymphoma. Pts had a median of 3 (range, 2-4) prior LOT, 28% had prior autologous hematopoietic cell transplantation, and 50% received bridging therapy. At 59.7 mo median follow-up, median PFS (95% CI) was 7.9 mo (6.3-10.9) and 5-y PFS was 30% (27-32). The median OS was 25.7 mo (21.6-30.2); 5-y OS was 38% (35-41). The 5-y cumulative incidence of disease-specific mortality was 51%. Among pts who were progression-free at 2, 3, 4, or 5 y post-infusion, the OS at 6 y (95% CI) was 73% (68-78), 81% (76-86), 90% (84-94), and 94% (89-97), respectively. The median duration of response (DOR) was 25.3 mo (95% CI, 20.7-32.8) and 5-y DOR was 38% (35-41). The median TTNT was 12.2 mo and 30% did not need additional LOT at 5 y. Of pts who received subsequent salvage therapy, 12 (2%) received cell therapy, 39 (7%) received hematopoietic cell transplant, and 475 (90%) received other therapy. The 1, 2, 3, 4, and 5-y cumulative incidence of relapse (95% CI) was 49% (46-51), 52% (50-55), 54% (52-57), 55% (53-58), and 56% (53-59), respectively. No new safety signals were observed. The primary causes of death (n=864; 60%) were primary disease (540; 63%), infection (111; 13%), and organ failure (57; 7%). The 5-y cumulative incidence of NRM was 16% (95% CI, 14-18). At 5 y, 11% (95% CI, 10-13) had subsequent malignancies, mostly therapy-related myeloid neoplasms (6%) and non-melanoma skin cancer (3%); none were directly attributed to axi-cel. Conclusions: This real-world study showed sustained survival at 5 y among pts with R/R LBCL treated with axi-cel after ≥2 LOT, consistent with ZUMA-1. Infection and organ failure were common causes of NRM. These results continue to support the use of axi-cel with curative intent in R/R LBCL.

632 Background: Prospective data on the risk of breast cancer (BC) recurrence among young BC survivors who have a subsequent pregnancy are limited. We sought to evaluate the long-term impact of pregnancy and live birth on BC outcomes in the Young Women’s Breast Cancer Study (NCT01468246), a prospective multicenter study of women aged ≤40 years at BC diagnosis. Methods: Women with stage 0-III BC without prior hysterectomy were included. The primary endpoint was breast cancer-free interval (BCFI) between patients with and without a (a) pregnancy and (b) live birth after BC. Secondary endpoints were distant recurrence-free interval (DRFI) and overall survival (OS). A time-varying Cox proportional hazards model was performed by estrogen receptor (ER) status, controlling for age at diagnosis, tumor stage, HER2 status, tumor grade, parity at diagnosis, and germline pathogenic variant status. Results: Among 1,016 BC survivors at a median follow-up of 12 (range, 0.5-18.5) years, 198 reported ≥1 pregnancy and 165 reported ≥1 live birth post-diagnosis. Among survivors who reported a post-diagnosis pregnancy, median age at diagnosis was 32 (range, 17-40) years; most had stage I (35%) or II (40%) BC, with 72% hormone receptor (HR)-positive and 25% HER2+; 42% were nulligravid and 60% were nulliparous at diagnosis. Among BC survivors who did not become pregnant post-diagnosis, median age at diagnosis was 37 (range, 21-40) years; most had stage I (35%) or II (43%) BC, with 75% HR-positive and 28% HER2+; 25% were nulligravid and 29% were nulliparous at diagnosis. Among BC survivors with ER-positive tumors (n = 737), pregnancy after BC was not associated with a difference in BCFI (adjusted hazard ratio [HR] 0.60, 95% CI 0.31-1.16, P = 0.130), DRFI (HR 0.73, 95% CI 0.35-1.55, P = 0.416), or OS (HR 0.58, 95% CI 0.24-1.40, P = 0.227). Similarly, live birth after BC did not impact BCFI (HR 0.83, 95% CI 0.45-1.55, P = 0.560), DRFI (HR 1.04, 95% CI 0.52-2.06, P = 0.923), or OS (HR 0.77, 95% CI 0.34-1.76, P = 0.541). Outcomes among BC survivors with ER-negative tumors (n = 278) were also not affected by post-diagnosis pregnancy (BCFI [HR 1.48, 95% CI 0.70-3.14, P = 0.304], DRFI [HR 1.59, 95% CI 0.68-3.75, P = 0.287], OS [HR 0.99, 95% CI 0.39-2.49, P = 0.975]) or live birth (BCFI [HR 1.02, 95% CI 0.41-2.53, P = 0.974], DRFI [HR 0.80, 95% CI 0.24-2.69, P = 0.722], OS [HR 0.39, 95% CI 0.09-1.69, P = 0.208]). Conclusions: In this multicenter, prospective study with 12 years of median follow-up, pregnancy and live birth after BC did not impact BC events or overall survival, irrespective of ER status. These long-term data from a modern cohort provide reassurance for young BC patients interested in future fertility. Clinical trial information: NCT01468246 .

4555 Background: TiNivo-2 results showed that immune checkpoint inhibitor (ICI) rechallenge did not offer benefit to patients with mRCC, regardless of treatment sequencing ( Lancet , 2024; 404:1309). However, the data highlights activity for Tivo monotherapy in the post-ICI setting. Long term outcomes of the TiNivo-2 study are reported here. Methods: TiNivo-2 trial design and primary-endpoint results were previously reported: patients with mRCC were randomized to treatment with Tivo 0.89 mg once daily for 21/28 days plus Nivolumab (Nivo) at 480 mg every four weeks (Tivo/Nivo) or Tivo 1.34 mg once daily for 21/28 days. Here, long term progression free survival (PFS), overall survival (OS), and the safety profile are reported at final analysis. Results: At the data cutoff of 17 October 2025, 172 patients were randomized to Tivo (171 treated) and 171 patients were randomized to Tivo/Nivo (168 treated); median (m) follow up was 28.4 mo (95% CI 27.0-29.8) in Tivo versus 27.2 months (mo) (95% CI 26.1-28.5) in Tivo/Nivo. Survival outcomes and hazard ratios (HR) for the ITT population, 2L, and 3L populations are summarized in Table 1. In 2L, mPFS favored Tivo over Tivo/Nivo (9.23 mo [7.29, 11.04] vs 5.95 mo [5.42, 7.95]). Across subgroups, there were no differences in mOS. No new safety signals were observed with prolonged administration; the most common ≥ Grade 3 TEAE was hypertension occurring in 39 (22.8%) and 38 (22.6%) and of patients in the Tivo and Tivo/Nivo groups respectively. Other ≥ Grade 3 TEAEs included diarrhea (2.3% and 3.6%) and palmar-plantar erythrodysaesthesia (0.6% and 1.2%) in the Tivo and Tivo/Nivo groups respectively. Treatment Related SAEs occurred in 15 (8.8%) and 18 (10.7%) of patients in Tivo and Tivo/Nivo groups respectively. Conclusions: This final analysis of patients in the TiNivo-2 study highlights the sustained efficacy Tivo in mRCC with a consistent safety profile. Together, these findings support durable clinical benefit and tolerability of Tivo in the post-ICI treatment setting in RCC, an area of high unmet need (NCT04987203). Clinical trial information: NCT04987203 . Parameter By ITT 2L setting 3L setting Tivo (0.89mg) /Nivo (n=171) Tivo (1.34mg) (n=172) Tivo (0.89mg) /Nivo (n=111) Tivo (1.34mg)(n=105) Tivo (0.89mg) /Nivo (n=60) Tivo (1.34mg)(n=67) mPFS, months (95% CI) 5.72(4.37-7.43) 7.43(5.52-9.23) 5.95(5.42, 7.95) 9.23(7.29, 11.04) 5.45(3.15, 9.56) 5.44(2.10, 7.36) mPFS HR 0.96 (0.76, 1.21) 1.08 (0.80, 1.46) 0.77 (0.52, 1.15) mOS, months (95% CI) 23.85(19.71-NR) 22.93 (18.14-NR) 29.50(21.06, NR) 23.52(18.33, NR) 19.71(10.81, 31.90) 22.70(11.79, NR) mOS HR 0.95 (0.70, 1.28) 0.78 (0.53, 1.16) 1.13 (0.70, 1.81) NR, not reached.