Fingerle-Rowson, Guenter

TPS3164 Background: TUB-030 is a novel antibody-drug conjugate (ADC) targeting 5T4, an oncofetal antigen expressed in various solid tumors with limited expression in healthy tissues. TUB-030 leverages optimized biophysical properties, an effector-silenced antibody, and an exatecan payload to maximize the therapeutic index and minimize off-target toxicities. Preclinical studies demonstrated potent anti-tumor activity, including long-lasting tumor regression at doses as low as 1 mg/kg and durable responses even in tumors with low 5T4 expression. Methods: 5-STAR 1-01 is a multicenter, first-in-human dose escalation and dose optimization Phase I/IIa clinical trial designed to investigate safety, tolerability, pharmacokinetics (PK), and efficacy of the anti-5T4 ADC TUB-030 in patients with advanced and metastatic solid tumors. Eligible patients have one of the following tumor types: head and neck squamous cell carcinomas (HNSCC), non-small-cell lung cancer (NSCLC), small cell lung cancer, pleural mesothelioma, triple-negative breast cancer, HR+/HER2- breast cancer, esophageal cancer, gastric cancer, pancreatic adenocarcinoma, colorectal cancer, bladder cancer, prostate cancer, cervical cancer, osteosarcoma, or soft tissue sarcomas and must have exhausted available standard-of-care therapies. Phase I is an open-label, single-arm dose escalation trial, with administration every 21 days. Dose escalation follows an accelerated titration design (ATD) transitioning to Bayesian optimal interval (BOIN) upon predefined toxicity thresholds. Backfill cohorts are planned in NSCLC and HNSCC to further evaluate the safety and efficacy profile at, or near, the maximum tolerated dose (MTD). Primary endpoints include safety and tolerability of TUB-030 as monotherapy, determination of the MTD and the recommended phase II doses; secondary endpoints assess pharmacokinetics, immunogenicity, and preliminary clinical activity using RECIST v1.1 criteria. Exploratory endpoints include analysis of circulating tumor DNA. In phase IIa, dose-optimization will evaluate two dose levels in select indications in order to identify the optimal dose for further development. Enrollment of approximately 130 patients across the US and Canada is planned, with dose escalation currently underway. This study investigates TUB-030, a novel 5T4 targeted ADC as a therapy for advanced/metastatic solid tumors. Clinical trial information: NCT06657222 .

8020 Background: Patients with R/R DLBCL ineligible for autologous stem cell transplant (ASCT) have a poor prognosis. In these patients, tafasitamab (anti-CD19 antibody) plus lenalidomide (LEN) has shown encouraging results in the open-label, single-arm, phase II L-MIND study (n = 81; NCT02399085). To evaluate the contribution of tafasitamab to the activity of this doublet, we conducted a global, real-world study of patients treated with LEN monotherapy (RE-MIND; NCT04150328). Here we present the primary analysis of a 1:1 patient-level matched comparison between the L-MIND and RE-MIND cohorts. Methods: Patients treated with LEN monotherapy for R/R DLBCL were enrolled in the observational, retrospective RE-MIND cohort. As in L-MIND, patients had 1–3 prior systemic therapies, including ≥1 CD20-targeting regimen; were aged ≥18 years; and were not eligible for ASCT. A 1:1 estimated propensity score (ePS) matching methodology ensured balancing of nine pre-specified baseline covariates. The primary analysis set, Matched Analysis Set 25 (MAS25), included patients who received a LEN starting dose of 25 mg/day. The primary endpoint was investigator-assessed best objective response rate (ORR). Key secondary endpoints included overall survival (OS) and complete response (CR) rate. Results: 490 patients were enrolled in RE-MIND across 58 centers in the US and Europe, of which 140 fulfilled the ePS matching criteria. The MAS25 included 76 patients each from the two cohorts. Baseline characteristics between cohorts were comparable. The primary endpoint was met with a significantly better ORR of 67.1% (95% CI: 55.4–77.5) for the L-MIND cohort versus 34.2% (95% CI: 23.7–46.0) for the RE-MIND cohort (odds ratio 3.89; 95% CI: 1.90–8.14; p < 0.0001). The CR rate was 39.5% (95% CI: 28.4–51.4) in the L-MIND cohort and 13.2% (95% CI: 6.5–22.9) in the RE-MIND cohort. A significant difference in OS favored the L-MIND cohort (HR = 0.499; 95% CI: 0.317–0.785). ORR and CR outcomes in the RE-MIND cohort were similar to the published literature for LEN monotherapy in R/R DLBCL. Conclusions: Significantly better ORR, CR and OS indicate potential synergistic effects of the tafasitamab + LEN combination in ASCT-ineligible R/R DLBCL. ePS-based 1:1 matching allows robust estimation of the treatment effect of tafasitamab when added to LEN. RE-MIND demonstrates the utility of real-world data in interpreting non-randomized trials. Clinical trial information: NCT04150328 .