Purpose: The next generation of theranostics studies is looking at novel combinations with radiation sensitizers to enhance peptide receptor radionuclide therapy’s efficacy. In this study, we present safety and efficacy data from a multicenter phase I study of a [177Lu]lutetium-dotatate–triapine combination in patients with gastroenteropancreatic (GEP) neuroendocrine tumors (NET). Patients and Methods: The study consisted of 2 phases (part A: dose escalation; part B: dose expansion) administering the recommended phase II doses (RP2D) for the 2 agents. All patients received 200 mCi of [177Lu]lutetium-dotatate on day 1 of four 8-week cycles, in combination with oral triapine administered at assigned dose levels (100, 150, or 200 mg) from day 1 to day 14 of each cycle. Results: A total of 31 (A: 15; B: 16) patients received treatment. Across the study, 9 patients experienced dose-limiting toxicities: grade 3 anemia (n = 1), grade 5 cardiac arrest (unrelated to investigational product; n = 1), and grade 4 neutropenia (n = 7). Based on the overall safety and pharmacokinetics data, a [177Lu]lutetium-dotatate (200 mCi) plus triapine (150 mg) dose was selected as the RP2D for the expansion phase. Grade ≥3 treatment-related adverse events were observed in 77% of patients: anemia (23%), nausea and vomiting (3%), lymphopenia (58%), neutropenia (35%), and decreased white blood cell count (39%). The majority of cytopenias were transient and resolved within 2 weeks. Among the 28 evaluable patients, the objective response rate was 21.4%, and the median progression-free survival has not been reached (median follow-up period, 23.7 months). Conclusions: The combination of [177Lu]lutetium-dotatate (200 mCi) and oral triapine (150 mg D1-14) was well tolerated and demonstrated preliminary activity in patients with well-differentiated GEP-NET (NCT04234568).

Normalized exposure matrix from Sigminer

Representativeness of study participants

Background: SCLC remains an aggressive malignancy with limited therapeutic options after progression. Tarlatamab, a DLL3-directed bispecific T-cell engager, has a demonstrated survival benefit in clinical trials, but real-world data remain limited. We evaluated the safety, radiographic response, and treatment durability of Tarlatamab in a real-world cohort treated at a single academic center. Methods: We performed a retrospective review of patients with extensive-stage SCLC who received Tarlatamab at the University of Miami Sylvester Comprehensive Cancer Center between 2024 and 31 October 2025. Demographic, clinical, radiographic, and toxicity data were abstracted from electronic medical records. Radiographic response was defined as partial response or stable disease on follow-up imaging. PFS and overall survival OS were estimated using the Kaplan–Meier method. Results: Twenty-three patients were included (median age 72 years), of whom 61% were Hispanic and 61% had brain metastases prior to treatment. Forty-three percent had received two or more prior lines of therapy. CRS and ICANS occurred primarily during Cycle 1 and were limited to grade 1–2 events, with no grade ≥3 toxicities. Median time on treatment was 92 days with a median of four cycles. Among 18 evaluable patients, partial response was observed in 27.7% and stable disease in 16.7%, yielding a disease control rate of 44.4%. Median PFS was 139 days and median OS was 323 days (95% CI, 31–614). Conclusions: In a predominantly Hispanic, heavily pre-treated real-world population with high CNS disease burden, Tarlatamab demonstrated feasible administration, manageable immune-mediated toxicity, and clinically meaningful antitumor activity.

Triapine geometric mean (SD) plasma pharmacokinetic parameters after PO administration