“This new dataset in metastatic triple-negative breast cancer is very exciting, and the ongoing randomized phase II part of the trial is a logical next step. We are very motivated to continue our collaboration with GEICAM on this study, with the aim of providing new therapeutic alternatives for this very difficult-to-treat disease,” said Göran Forsberg, CEO of Cantargia.

In the dose escalation stage of the phase Ib/II TRIFOUR trial, five first-line and ten second-line patients with metastatic TNBC were treated with nadunolimab in combination with gemcitabine and carboplatin. Interim analysis of these 15 patients shows one confirmed complete response (CR) and eight confirmed partial responses (PR), bringing a preliminary total response rate (RR) to 60%. The current median progression-free survival (PFS) is 6.6 months, and an early estimate of median overall survival (OS) is 12.3 months. This compares favorably to historical data for gemcitabine and carboplatin alone, which shows 30% RR, 4.1 months median PFS and 11.1 months median OS [1]. The recommended phase II dose of nadunolimab was 2.5 mg/kg, which is currently investigated in the ongoing phase II part of the trial.

The safety profile of the combination is similar to previous reports for the chemotherapy only. The most frequently reported grade 3 or 4 adverse events were neutropenia (53%) and thrombocytopenia (27%), in line with previous trials for this chemotherapy regimen alone (53% and 24%, respectively) [1]. Notably, prophylactic use of G-CSF was used to manage neutropenia.

TRIFOUR, performed in collaboration with GEICAM Spanish Breast Cancer Group, progressed to the randomized phase II part in Q1 2023. Based on the promising phase Ib data presented today, and with no new safety signals emerging in the phase II part, a protocol amendment will be submitted to continue enrollment to TRIFOUR until full recruitment without an interim futility analysis. Implementation of this action requires regulatory and ethics committee approval. Top-line analysis for the complete trial is planned after full recruitment, estimated late 2024 or early 2025.

“Triple-negative breast cancer has the poorest prognosis among breast cancer subtypes and has very limited treatment options. The data presented today indicate a promising early signal of efficacy, which we are very eager to explore further in the randomized stage of TRIFOUR,” said Dr. Sara López-Tarruella, member of the Steering Committee of GEICAM, Coordinator of the GEICAM Working Group in Triple Negative Breast Cancer, and one of the Chief Investigators of the TRIFOUR study.

Details of the poster session at ESMO 2023 can be found below. The poster is also available at Cantargia’s webpage (link). A poster abstract based on a less mature read-out was disclosed on 16 October 2023.

Abstract title: Phase Ib safety and efficacy of nadunolimab/gemcitabine/carboplatin (NadGC) in metastatic triple negative breast cancer (mTNBC)
Date and time: October 21, 2023, 12:00 – 1:00 PM CEST
Presenter: Dr. Sara López-Tarruella

References
[1] O’Shaughnessy, J Clin Oncol 2014, 32:3840-3847