NCT05181462: TRIFOUR

A Randomized Non-comparative Open-label Phase 1b/2 Study of Nadunolimab in Combination With Gemcitabine Plus Carboplatin in Patients With Advanced Triple Negative Breast Cancer. "TRIFOUR Study"

Completed Phase 1/Phase 2 Last updated 22 May 2026

What this trial tests

Phase 1/Phase 2 trial testing Carboplatin in Triple Negative Breast Cancer in 117 participants. Completed in 8 May 2026.

Timeline

11 January 2022

Primary endpoint
9 April 2026

8 May 2026

Quick facts

Lead sponsor	Cantargia AB
Phase	Phase 1/Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	117
Start date	11 January 2022
Primary completion	9 April 2026
Estimated completion	8 May 2026
Sites	23 locations across Spain

Drugs / interventions tested

• Carboplatin (Carboplatin) — full drug profile →
• Gemcitabine (gemcitabine) — full drug profile →
• Nadunolimab — full drug profile →

Conditions studied

• Triple Negative Breast Cancer — all drugs for Triple Negative Breast Cancer →

Sponsor

Cantargia AB — full company profile →

Who can join

18 and older, any sex, with Triple Negative Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Incidence rate of Dose Limiting Toxicity (DLT) within the first cycle of nadunolimab in combination with gemcitabine plus carboplatin
  Time frame: At the end of Cycle 1 (each cycle is 21 days)
  DLT is defined according to the NCI-CTCAE version 5.0 as any of the following events considered by investigator to be related to investigational treatment: 1. Grade (G) 5 Treatment Emergent AE 2. G ≥ 3 neutropenia + fever and/or infection (single temp. \> 38.3°C or sustained temp. ≥ 38°C \>1 hour) 3. G 4 neutropenia \> 7 days 4. G 4 thrombocytopenia \> 3 days 5. G ≥ 3 thrombocytopenia \> 7 days o
• Objective Response Rate (ORR)
  Time frame: Through study completion, an average of 58 months
  Tumor response is assessed according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1 as per investigators' assessment. ORR is defined as the rate of Complete Response (CR) plus Partial Response (PR) according to RECIST version 1.1, out of the patients who receive at least one dose of treatment and have measurable disease. These results will be calibrated against the ORR in t

Sponsor's own description

Triple negative breast cancer (TNBC) represents approximately 15% of all breast cancers (BC) worldwide. The term triple negative means that tumor growth is not stimulated by the hormones estrogen and progesterone, nor by the HER2 protein, so unlike other types of BC, TNBC, which is an aggressive form of BC, does not have specific effective therapies available being the least common form of BC and the most difficult to treat.

Advanced or metastatic TNBC is treated with combinations of platinum-based chemotherapy with taxanes or gemcitabine with a 5-year survival rate of 12%. Recent studies have shown that TNBC expresses Interleukin 1 Receptor Accessory Protein (IL1RAP) at higher levels than other forms of BC.

Nadunolimab is a fully humanized monoclonal antibody that blocks the signals that occur within the cell produced by IL1RAP protein, thereby impairing the cancer cells' ability to secrete tumor stimulating substances, in turn reducing the tumor, inflammation and tumor progression. On the other hand, it is an antibody designed to activate the immune system to fight cancer cells.

This clinical trial is divided into two phases, phase Ib in which it is expected to include up to 15 patients and phase II in which it is expected to include 102 patients. The main purpose of phase Ib is to ensure that the combination of nadunolimab plus chemotherapy (gemcitabine plus carboplatin) is safe and determine the highest dose of nadunolimab that can be given safely without causing serious side effects. If the pre-specified objectives in this part are achieved, the trial will be expanded to a randomized phase II, to evaluate the efficacy of the combination of nadunolimab plus gemcitabine plus carboplatin, compared to a control group that will receive gemcitabine plus carboplatin only.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. IL-1RAP, a Key Therapeutic Target in Cancer.
   Frenay J, Bellaye PS, Oudot A, Helbling A, et al · · 2022 · cited 20× · PMID 36499246 · DOI 10.3390/ijms232314918
2. Interleukin-1 receptor accessory protein blockade limits the development of atherosclerosis and reduces plaque inflammation.
   Mulholland M, Depuydt MAC, Jakobsson G, Ljungcrantz I, et al · · 2024 · cited 15× · PMID 38563353 · DOI 10.1093/cvr/cvae046
3. IL1RAP-specific T cell engager depletes acute myeloid leukemia stem cells.
   Zhang Y, Park M, Ghoda LY, Zhao D, et al · · 2024 · cited 14× · PMID 39143574 · DOI 10.1186/s13045-024-01586-x
4. The Present and Future of Clinical Management in Metastatic Breast Cancer.
   Lin PH, Laliotis G. · · 2022 · cited 14× · PMID 36233758 · DOI 10.3390/jcm11195891
5. Antibodies targeting the shared cytokine receptor IL-1 receptor accessory protein invoke distinct mechanisms to block all cytokine signaling.
   Fields JK, Gyllenbäck EJ, Bogacz M, Obi J, et al · · 2024 · cited 8× · PMID 38636519 · DOI 10.1016/j.celrep.2024.114099
6. MicroRNA-142 improves IL1RAP CAR-T cell activity in acute myeloid leukemia.
   Harada K, Zhao D, Park M, Chen F, et al · · 2025 · cited 1× · PMID 41225489 · DOI 10.1186/s13045-025-01755-6
7. Tumor Microenvironment Onmyoji: Cytokines with Dual Protumor and Antitumor Roles.
   Wang Y, Lin A, Liu Z, Cheng Q, et al · · 2026 · PMID 41625477 · DOI 10.34133/cancomm.0008