UTD1 Receives FDA Orphan Drug Designation in Breast Cancer Brain Metastasis


Utidelone injectable has received FDA orphan drug designation for patients with breast cancer brain metastases.



The FDA has granted orphan drug designation to utidelone injectable (UTD1) as a potential therapeutic option for patients with breast cancer brain metastases, according to an announcement from Biostar Pharma.1 Unlike most macromolecular drugs, utidelone can cross the blood-brain barrier because of its unique physiochemical characteristics and its insusceptibility to P-glycoprotein–mediated efflux.

The orphan drug designation was based on data from 2 phase 2 trials. In the phase 2 UTOBIA-BM trial (NCT05781633) of UTD1 plus etoposide and bevacizumab (Avastin), the combination elicited a central nervous system (CNS) overall response rate (ORR) of 73% and a CNS clinical benefit rate (CBR) of 91% in patients with HER2-negative breast cancer brain metastases (n = 17). Another phase 2 trial (NCT05357417) evaluating utidelone plus bevacizumab showed a median progression-free survival (PFS) of 7.7 months and a 12-month overall survival (OS) rate of 74.4% in patients with HER2-negative breast cancer brain metastases (n = 46).

The single-arm UTOBIA-BM trial enrolled female patients at least 18 years of age with an ECOG performance status (PS) of 0 to 2 and a life expectancy of at least 12 weeks.2 Other enrollment criteria included: untreated breast cancer brain metastases that do not require immediate local treatment; previously treated breast cancer brain metastases that have progressed after prior CNS local treatment; no history of chemotherapy, radiotherapy, surgery, targeted therapy, or immunotherapy within 4 weeks prior to enrollment; toxicities associated with prior antitumor therapy that were restored to grade 1 or lower; normal routine blood tests within 1 week prior to enrollment; and basically normal kidney and liver function. Patients with HER2-positive disease were also required to have received prior HER2-directed therapy and TKI therapy.

Patients received UTD1 at 30 mg/m2 on days 1 through 5, intravenous (IV) etoposide at 100 mg/m2 on days 1 through 3, and IV bevacizumab at 10 mg/kg on day 1 of each 21-day cycle for 6 cycles. This was followed by UTD1 and bevacizumab maintenance therapy until patients experienced unacceptable toxicity or disease progression.3 The primary end point of this trial was CNS ORR. Key secondary end points included CNS CBR, CNS PFS, ORR for non-CNS lesions, CBR for non-CNS lesions, ORR, PFS, CBR, OS, and safety.

At a data cutoff of May 5, 2023, 11 patients were evaluable for response, had received a median of 6 cycles (range, 2-8), and were all still receiving treatment. The ORR and CBR were 64% and 91%, respectively. The ORR and CBR for non-CNS lesions were 27% and 55%, respectively. The median PFS and OS were not yet reached (NR).

Cohort 1 of the other phase 2 trial enrolled patients at least 18 years of age with HER2-negative advanced breast cancer with brain metastases who have received at least 1 prior anthracycline and at least 1 prior taxane.4 Cohort 2 of this trial enrolled patients with HER2-positive advanced disease who had progressed on trastuzumab and pyrotinib and had at least 1 measurable CNS lesion. Patients needed to have prior unproved treatment progression with bevacizumab or utidelone; an ECOG PS of 0 or 1; a life expectancy of longer than 12 weeks; normal organ, bone marrow, kidney, and liver function; and a normal blood sample within 1 week before enrollment.

Patients in both cohorts received bevacizumab at 15 mg/kg on day 1 and utidelone at 30 mg/m2 (± 10%) on days 1 through 5 of every 3-week cycle until unacceptable toxicity or disease progression. The primary end point of this trial was CNS ORR per RECIST v1.1 criteria. Key secondary end points included CNS ORR per Response Assessment in Neuro-Oncology criteria, investigator-assessed CNS PFS, extracranial ORR, extracranial PFS, OS, time to whole-brain radiotherapy, quality of life, and safety.

Utidelone’s ability to cross the blood-brain barrier and its therapeutic potential for brain tumors has influenced Biostar Pharma’s plans to advance clinical trials of UTD1 in other brain tumors, including glioma and lung cancer brain metastasis.1 These trials are expected to launch in 2024.


  1. 73% CNS ORR! FDA granted ODD to utidelone injectable (UTD1) from Biostar Pharma for the treatment of breast cancer brain metastasis. News release. Biostar Pharma, Inc. March 29, 2024. Accessed April 1, 2024. https://www.prnewswire.com/news-releases/73-cns-orr-fda-granted-odd-to-utidelone-injectable-utd1-from-biostar-pharma-for-the-treatment-of-breast-cancer-brain-metastasis-302103497.html#:~:text=SAN%20FRANCISCO%2C%20March%2029%2C%202024,that%20their%20core%20pipeline%20product
  2. The efficacy and safety of eutideron, etoposide, and bevacizumab in patients with brain metastases from breast cancer. ClinicalTrials.gov. Updated March 23, 2023. Accessed April 1, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05781633
  3. Shi Y, Wang P, Zhu Y, et al. Utidelone in combination with etoposide and bevacizumab in HER2-negative breast cancer with brain metastases (UTOBIA-BM): a prospective, single-arm, phase II trial. Ann Oncol. 2024;34(suppl 2):S349-S350. doi:10.1016/j.annonc.2023.09.578
  4. Utidelone plus bevacizumab for advanced breast cancer with brain metastases. ClinicalTrials.gov. Updated September 16, 2022. Accessed April 1, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05357417
Related Videos
Samilia Obeng-Gyasi, MD, MPH,
Nan Chen, MD
Timothy Yap, MBBS, PhD, FRCP
Parul N Barry, MD,
Erin Frances Cobain, MD
Erin Frances Cobain, MD
Video 6 - "Shared Decision Making and Multidisciplinary Collaboration in the Evolving HR+/HER2- Early-Stage Breast Cancer Landscape"
Manmeet Singh Ahluwalia, MD
Rita Nanda, MD
Video 5 - "AE Management with CDK4/6 Inhibitors: Strategies for Treatment Continuity and Optimal Patient Outcomes"