Safety and preliminary efficacy of adding tocilizumab to cisplatin/docetaxel for the treatment of locally advanced triple-negative breast cancer patients - prospective phase 1/2 clinical trial

Sep 23, 2026

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Prospective phase 1/2 clinical trial evaluating the safety and preliminary efficacy of tocilizumab (Actemra) added to cisplatin/docetaxel for locally advanced triple-negative breast cancer. Participants received tocilizumab on day 1, followed by cisplatin/docetaxel on day 2 every four weeks for six cycles using a traditional 3+3 design with sentinel patients. Safety/tolerability was the primary endpoint; efficacy and pathological complete response in breast and axilla were secondary endpoints. BRCA1/2 status was assessed by DNA sequencing. In 30 patients, overall pCR reached 62% with axillary pCR of 81%.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

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Background

Rationale for targeting IL-6 in TNBC

Study design and treatment schedule

Primary objective: safety run-in

Secondary endpoints: efficacy and pCR

Patient characteristics and biomarker assessment

BRCA1/2 sequencing

Efficacy outcomes

Overall pCR and axillary pCR

Safety and tolerability conclusions

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Safety and preliminary efficacy of adding tocilizumab to cisplatin/ docetaxel for the treatment of locally advanced triple-negative breast cancer patients: prospective phase 1/2 clinical trial Taher Al-Tweigeri1􀀍, AsmaTulbah3, Syed Akhtar1, MeshariAlzahrani1, Saleh Najjar3, Tusnem El Hassan1, Noura N. Alraouji2, Kauser Suleman1, Adher AlSayed1 & Abdelilah Aboussekhra2􀀍 Triple-negative breast cancer (TNBC) remains a challenge for clinicians due to its aggressive behavior and scarcity of effective treatment. Interleukin 6 (IL-6) is well known to contribute to poor therapeutic gain, tumor relapse, and aggressive tumor growth. Here, we have explored targeting the IL-6 signaling pathway by tocilizumab (Actemra) as a new potential therapeutic approach for the treatment ofTNBC patients. The participants were treated uniformly with tocilizumab on day 1, followed by cisplatin/docetaxel on day 2 every 4 weeks for a total of six cycles according to a traditional 3 + 3 design using a sentinel patient in each cohort. The primary objective of the safety run-in was tolerability/toxicity profiles, while the secondary endpoints included efficacy and pathological complete response (pCR) in breast and axilla (ypT0/ypN0) . The status of the BRCA1 and BRCA2 genes was determined by DNA sequencing in all patients. Thirty (30) patients with (T2-T4, N0-3) stage (IIB-III) TNBC were included in this phase I/II trial. They hada median age of 42 years, 63% were premenopausal, and 67% had nodal involvement at baseline. The median tumor size was 45 mm (range 25–150 mm), stage IIIA/B 26% and stage IIIC 50% . Germline BRCA1/2 mutations represented 27% of the patients. All assessable patients (n = 28) underwent surgery after neoadjuvant therapy (tocilizumab plus chemotherapy) . The overall pCR (RCB class 0) was 62%, and pCR in the axilla was reached by 81% of the treated patients. Patients with tumors bearing mutated BRCA1/2 achieved a 100% pCR rate. The present clinical trial shows that tocilizumab-dependent inhibition of the IL-6 signaling in a sequential fashion with chemotherapy is safe and tolerable for neoadjuvant treatment of the intricate and hard-to-treat TNBC patients. Trial registration: ISRCTN50182475 “Safety and effectiveness of tocilizumab followed by cisplatin/docetaxel in advanced triplenegative breast cancer”(retrospective registration 19/03/2025) . [https://doi.org/10.1186/ISRCTN50182475](https://doi.org/10.1186/ISRCTN50182475. SCTR 19)[. SCTR 19](https://doi.org/10.1186/ISRCTN50182475. SCTR 19),111,002 (Saudi Food and Drug Authority)“Singlearm Phase I/II study of the safety, tolerability and efficacy of the Tocilizumab followed by cisplatin/docetaxel in patients with triple negative locally advanced breast cancer”(registration date 12/03/2020) . Keywords Tocilizumab, Triple-negative breast cancer, Interleukin-6, Clinical trial 1Department of Medical Oncology, Cancer Center of Excellence, King Faisal Specialist Hospital and Research Center, MBC \# 64, PO BOX 3354, 11211 Riyadh, Kingdom of Saudi Arabia. 2Department of Research Laboratories, King Faisal Specialist Hospital and Research Center, MBC\#03, PO BOX 3354, 11211 Riyadh, Kingdom of Saudi Arabia. 3Department of Pathology, King Faisal Specialist Hospital and Research Center, MBC\#03, PO BOX 3354, 11211 Riyadh, Kingdom of Saudi Arabia. 􀀍 [email: ttwegieri@kfshrc.edu.sa](email: ttwegieri@kfshrc.edu.sa); [aboussekhra@kfshrc.edu.sa](aboussekhra@kfshrc.edu.sa) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) Abbreviations AEs ALTAST BCSBRCA1/2 DFSECOGER FISH GCP HER2 IHCIDC IL-6 IL-6RIRB MRIMTDNACT NCI CTCAE ORROS pCR PR PETCTRCBRP2DSFDA sIL-6R sTILs TILs TNBC MTDDLT RD Adverse events Alanine aminotransferase Aspartate aminotransferase Breast conserving surgery Breast Cancer gene 1/2 Disease-free survival Eastern Cooperative Oncology Group Estrogen recepto

FAQs

What was the main objective of the phase 1/2 trial?

The primary objective was the safety run-in, focusing on tolerability and toxicity profiles.

How were patients treated during the study?

Participants received tocilizumab on day 1, then cisplatin/docetaxel on day 2 every four weeks for six cycles, following a traditional 3+3 design.

What efficacy results were reported for pathological complete response?

Overall pathological complete response (RCB class 0) was 62%, and axillary pCR was achieved by 81% of treated patients.

Sep 23, 2026

Uploaded by Connor