Objectives Describe the time elapsed from the diagnosis to treatment with chemotherapy for patients with breast and lung cancer at public and private hospitals in Buenos Aires. Design Retrospective cohort study. Setting Three public and three private academic hospitals in Buenos Aires. Participants Patients with breast (n = 168) or lung cancer (n = 100) diagnosis treated with chemotherapy. Main outcomes measures Clinical and sociodemographic data were collected in a stratified sample. We used the Kaplan–Meier estimator to analyse the time elapsed and the log rank test to compare both groups Results For breast cancer patients, median time elapsed between diagnosis and treatment with chemotherapy was 76 days (95% CI: 64–86) in public and 60 days (95% CI: 52–65) in private hospitals (P = 0.0001). For adjuvant and neoadjuvant treatments, median time was 130 (95% CI: 109–159) versus 64 (95% CI: 56–73) days (P < 0.0001) and 57 days (95% CI: 49–75) versus 26 (95% CI: 16–41) days, respectively (P = 0.0002). There were no significant differences in the time from first consultation to diagnosis. In patients with lung cancer, median time from diagnosis to treatment was 71 days (95% CI: 60–83) in public hospitals and 31 days (95% CI: 24–39) in private hospitals (P = 0.0002). In the metastatic setting, median time to treatment was 63 days (95% CI: 45–83) in public and 33 (95% CI: 26–44) days in private hospitals (P = 0.005). Conclusions There are significant disparity in the access to treatment with chemotherapy for patients in Buenos Aires, Argentina.

432 Background: Pembro monotherapy is a standard of care for advanced urothelial carcinoma (UC) and showed antitumor activity and acceptable safety when combined with lenva in the phase 1b/2 KEYNOTE-146 study. We present results of LEAP-011 (NCT03898180), a randomized, double-blind, multicenter, global, phase 3 study of first-line pembro + lenva vs pembro + placebo in pts with locally advanced or metastatic UC who are cisplatin-ineligible with PD-L1–positive tumors or are ineligible to receive platinum-based chemotherapy. Methods: Adults with histologically confirmed, locally advanced/unresectable or metastatic UC who were cisplatin-ineligible with tumors expressing PD-L1 (combined positive score ≥10) or were ineligible to receive platinum-based chemotherapy regardless of PD-L1 status were randomly assigned 1:1 to receive pembro 200 mg IV Q3W for up to 35 cycles (̃2 y) + either lenva 20 mg orally once daily or placebo. Primary end points were PFS per RECIST v1.1 and OS. The key secondary end point was ORR per RECIST v1.1. An independent data monitoring committee (DMC) regularly reviewed safety data every 3 months; for the 6th review, a nonbinding futility analysis to evaluate ORR (−1%) and PFS (HR ≥1.1) was performed. There was no futility bound for OS. Results: Of 441 randomly assigned pts, 218 were assigned to receive pembro + lenva (median age, 74 y [range, 43-93]; ECOG PS 2, 83.5%) and 223 (median age, 73 y [range, 47-92]; ECOG PS 2, 83.0%) were assigned to receive pembro + placebo. Median duration of treatment was 3.8 mo (range, 0.0-20.7) for pembro + lenva and 3.4 mo (range, 0.0-22.0) for pembro + placebo. Median PFS was 4.2 mo (95% CI, 3.8-5.9) in the pembro + lenva group and 4.0 mo (95% CI, 2.7-5.4) in the pembro + placebo group (HR, 0.91 [95% CI, 0.71-1.16]). Median OS was 11.2 mo (95% CI, 7.4-14.9) with pembro + lenva vs 13.8 mo (95% CI, 9.8-18.8) with pembro + placebo (HR, 1.25 [95% CI, 0.94-1.67]; 6-mo OS rate, 63.6% vs 70.7%). ORR was 31.2% with pembro + lenva vs 26.5% with pembro + placebo. In 436 treated pts, treatment-related AEs (TRAEs) occurred in 186 of 214 pts (86.9%) in the pembro + lenva group and in 149 of 222 pts (67.1%) in the pembro + placebo group. Grade 3-5 TRAEs occurred in 107 pts (50.0%) in the pembro + lenva group and in 62 pts (27.9%) in the pembro + placebo group. Death from a TRAE occurred in 6 pts (2.8%) in the pembro + lenva group and in 1 pt (0.5%) in the pembro + placebo group. Conclusions: The safety profile of pembro + lenva was consistent with that of previous studies; no new safety signals were observed. The benefit/risk ratio for pembro + lenva was not considered positive vs pembro + placebo in platinum-ineligible pts with advanced UC. Antitumor activity of pembro + placebo was similar to what has been reported in previous studies, and pembro monotherapy remains standard of care as first-line therapy in platinum-ineligible pts with advanced UC. Clinical trial information: NCT03898180.

TPS596 Background: Radical cystectomy (RC) without neoadjuvant chemotherapy remains SOC for cis-ineligible pts (and those refusing cis) with MIBC and T1-T4aN1 disease. Yet, many pts progress to incurable, metastatic disease. Preventing disease recurrence for these pts remains an unmet need. Immune checkpoint inhibitors (ICIs) are approved in Bacillus Calmette-Guérin-unresponsive carcinoma in situ, in the adjuvant and metastatic urothelial cancer (UC) settings, and are being actively explored in the perioperative setting. In phase 2 single-arm trials, neoadjuvant ICIs showed promising pathologic complete response (pCR) rates (approximately 30%–40%). The phase 3 CheckMate 274 study showed improved disease-free survival with adjuvant NIVO vs placebo in MIBC. BEMPEG, an immunostimulatory interleukin-2 (IL-2) cytokine prodrug, is engineered to deliver a controlled, sustained, and preferential signal to the clinically validated IL-2 pathway. Preferential binding of BEMPEG to the IL-2 heterodimeric receptor (IL-2Rβγ) activates and expands CD8+ T cells and natural killer cells over immunosuppressive regulatory T cells. The combination of BEMPEG + NIVO demonstrated deep responses and a tolerable safety profile in pts with metastatic UC in the phase 1/2 PIVOT-02 trial and is being further explored in the phase 2 PIVOT-10 (NCT03785925) study. The PIVOT IO 009 study, presented here, aims to evaluate the hypothesis that perioperative treatment with BEMPEG + NIVO will provide higher pCR and longer event-free survival (EFS) vs SOC in cis-ineligible pts with MIBC and T1-T4aN1 disease. Methods: PIVOT IO 009 (NCT04209114) is an open-label, phase 3 trial of 540 cis-ineligible pts with MIBC and T1-4aN1 disease, who will be randomized 1:1:1 to receive SOC, neoadjuvant and adjuvant BEMPEG + NIVO, or neoadjuvant and adjuvant NIVO alone. Stratification factors include clinical stage (T2N0 vs T3-T4aN0 vs T1-T4aN1) and tumor cell PD-L1 status. Key inclusion criteria: adults with MIBC and T1-T4aN1 disease deemed eligible for RC and ECOG PS 0–1. Cis-ineligibility is defined as one of the following: glomerular filtration rate ≥30 but < 60 mL/min, or ≥grade 2 hearing loss or peripheral neuropathy. Key exclusion criteria: clinical evidence of ≥N2 or metastatic disease or UC in the upper urinary tract; prior systemic therapy, radiation therapy, or prior surgery for bladder cancer other than TURBT or biopsies. Primary endpoints: pCR rate (pT0N0) of neoadjuvant BEMPEG + NIVO vs no neoadjuvant therapy (SOC), and EFS of neoadjuvant and adjuvant BEMPEG + NIVO vs SOC. Secondary endpoints: pCR rate of neoadjuvant NIVO vs SOC; EFS of neoadjuvant and adjuvant NIVO vs SOC; overall survival and safety in each treatment arm vs SOC. The study is currently recruiting pts. Clinical trial information: NCT04209114.

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4506 Background: In part A of the CheckMate 914 trial, adjuvant nivolumab plus ipilimumab (NIVO+IPI) did not improve disease-free survival (DFS) vs placebo (PBO) in patients (pts) with localized renal cell carcinoma (RCC) at high risk of post-nephrectomy relapse (Motzer RJ, et al. Lancet 2023). Exploratory analyses were conducted to better understand outcomes in key pt subsets and with early NIVO+IPI discontinuation. Methods: Key study inclusion criteria were radical/partial nephrectomy with negative margins > 4 and ≤ 12 weeks before randomization; predominant clear cell histology; pathological TNM stage T2a (grade [G] 3/4) N0M0, T2b-T4 (any G) N0M0, or any pT (any G) N1M0; and no evidence of residual disease/metastases. Pts in part A were randomized 1:1 to NIVO 240 mg Q2W (× 12) + IPI 1 mg/kg Q6W (× 4) or equivalent PBO for 24 weeks or until recurrence/unacceptable toxicity. Primary endpoint is DFS per blinded independent central review. Exploratory analyses assessed DFS by key subsets including Fuhrman grade, sarcomatoid features (yes/no), PD-L1 expression, and NIVO+IPI exposure (≤ 6 cycles [1–2 IPI doses] vs > 6 cycles [3–4 IPI doses]). Safety was assessed by exposure. Results: 816 pts were randomized to adjuvant NIVO+IPI (N = 405) or PBO (N = 411). At 37.0 months median follow-up (min, 15.4 months), subset analyses suggested a DFS benefit for NIVO+IPI vs PBO in pts with Fuhrman grade 4 or sarcomatoid features. DFS by PD-L1 expression will be reported in the presentation. Pts who received > 6 NIVO+IPI cycles trended toward improved DFS vs pts receiving ≤ 6 NIVO+IPI cycles. Of the 102 pts who received ≤ 6 NIVO+IPI cycles, 3% had sarcomatoid features, and 20% had Fuhrman grade 4; treatment discontinuation in these pts was due to study drug toxicity (75%), unrelated adverse events (AEs; 6%), pt request (5%), recurrence (4%), consent withdrawal/non-compliance (4%), or other (6%), and most pts receiving ≤ 6 NIVO+IPI cycles were discontinued without initial dose delay (NIVO, 84%; IPI, 89%). In the group of patients who received ≤ 6 NIVO+IPI cycles, grade 1–2 all-cause AEs were reported in 35% of pts (grade ≥ 3, 63%) and 31% of pts discontinued treatment due to grade 1–2 all-cause AEs (grade ≥ 3, 44%). Conclusions: Exploratory analyses suggest that tumor grade and sarcomatoid features influence outcomes with adjuvant NIVO+IPI. Limited NIVO+IPI exposure (≤ 6 cycles) and discontinuation for low-grade AEs may have contributed to the lack of DFS benefit observed in CheckMate 914 part A. Clinical trial information: NCT03138512 . [Table: see text]