Study of Cirmtuzumab and Paclitaxel for Metastatic or Locally Advanced, Unresectable Breast Cancer

NCT02776917 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 160178
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot phase 1b study to investigate the safety and side effects of combining the ROR1-targeting monoclonal antibody, cirmtuzumab, with paclitaxel for patients with HER2 negative, metastatic breast cancer. Cirmtuzumab is a type of drug called a monoclonal antibody. This drug is designed to attach to a protein called receptor-tyrosine-kinase like orphan receptor 1 (ROR1) on the surface of breast cancer cells. Cirmtuzumab blocks the growth and survival of the breast cancer cells in laboratory tests. ROR1 is rarely expressed on healthy cells. Cirmtuzumab is considered experimental and is not approved by United States (U.S.) Food and Drug Administration (FDA).

Conditions

Breast Neoplasms

Keywords

metastatic breast cancer; locally advanced, unresectable breast cancer; HER2/NEU negative

Outcome Measures

Primary Outcomes (1)

• Dose-limiting Toxicities During the First 4 Weeks of Treatment

  Clinically significant adverse events per CTCAE Version 4.03 at least possibly related to cirmtuzumab or the combination of cirmtuzumab and paclitaxel during the first four weeks of investigational treatment.

  Within 4 weeks of starting study treatment

Secondary Outcomes (3)

• Number of Participants With Treatment-emergent Adverse Events

  55 weeks

• Objective Tumor Response Rate

  55 weeks

• Best Tumor Response Rate

  12 months

Study Arms (1)

Cirmtuzumab + Paclitaxel

EXPERIMENTAL

Cirmtuzumab 600 mg is administered intravenously on Days 1 and 15 of the first 28-day cycle, then on Day 1 of each subsequent 28-day cycle. Paclitaxel 80 mg/m\^2 is administered weekly on Days 1, 8, 15, and 22 of each 28-day cycle.

Drug: Cirmtuzumab + Paclitaxel

Interventions

Cirmtuzumab + Paclitaxel DRUG

Cirmtuzumab and paclitaxel may be administered until disease progression or unacceptable toxicity. Cirmtuzumab or paclitaxel may be continued alone if the other drug is discontinued due to toxicity.

Also known as: UC-961 or Zilovertamab, Taxol

Cirmtuzumab + Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy-confirmed, metastatic or locally advanced surgically unresectable, HER2 negative breast cancer. HER2 status should reflect the most recent biopsy results. Note: HER2 negative breast cancer is defined according to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines 2013 for HER2 testing performed in a CLIA-certified laboratory.
• ER/PR negative (\<10% of cells staining for ER or PR) breast cancer or have ER/PR positive (≥10% of cells staining for ER or PR) breast cancer that has exhausted standard endocrine therapy and/or in the opinion of the treating oncologist, warrants cytotoxic chemotherapy.
• Measurable disease as defined by RECIST v1.1. Measurable lesions will be confirmed by radiographic imaging (CT or MRI). Patients with bone only disease will be eligible if disease is considered measurable and a soft tissue component is present and can be biopsied..
• There is no limit to prior lines of therapy, but patients must not have received prior taxane chemotherapy in the metastatic setting.
• ECOG Performance Status ≤ 2.
• Adequate organ function as defined below:
• Absolute Neutrophil Count ≥ 1.0 x 10\^9/L
• Platelet count ≥ 100,000 /μL
• Hemoglobin ≥ 8.0 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal
• AST and ALT ≤ 3 x upper limit of normal
• Serum creatinine ≤ 2 x upper limit of normal OR Creatinine clearance \> 40 ml/min/1.73 m\^2
• Women of child-bearing potential and male subjects who are sexually active with a woman of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 6 months following last infusion of cirmtuzumab. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Existing neuropathy must be no greater than Grade 1.
• No concurrent antibody therapy can be planned with the exception of denosumab for use in bone metastasis.

You may not qualify if:

• Patient is currently receiving chemotherapy or has received another chemotherapy within 5 half-lives, radiotherapy or immunotherapy within 2 weeks prior to study treatment initiation.
• Patient has known, untreated and/or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Patient had disease that was refractory to paclitaxel in the neoadjuvant setting and/or developed metastatic breast cancer within 6 months of neoadjuvant or adjuvant taxane chemotherapy.
• Patient has had major surgery within 3 weeks prior to enrollment.
• Patient has severe and/or uncontrolled medical disease(s) (i.e., myocardial infarction within 6 months of study, CKD stage IV or above, severe chronic pulmonary disease or active infection).
• The patient has known acute or chronic hepatitis B or C.
• The patient has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel.
• The patient has a history of another malignancy within 2 years prior to study entry, except curatively treated non-melanotic skin cancer, cervical carcinoma in situ or stage I colon cancer.
• Patient has a history of non-compliance or other medical illness that would preclude compliance with study procedures.
• Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
• Patient has severe cardiac insufficiency (NYHA III or IV) with uncontrolled and/or unstable cardiac or coronary artery disease
• Patient is pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants.

Sponsors & Collaborators

• Barbara Parker, MD: lead
• Oncternal Therapeutics, Inc: collaborator

Study Sites (1)

University of California, San Diego

La Jolla, California, 92093, United States

Location

Related Publications (1)

• Shatsky RA, Batra-Sharma H, Helsten T, Schwab RB, Pittman EI, Pu M, Weihe E, Ghia EM, Rassenti LZ, Molinolo A, Cabrera B, Breitmeyer JB, Widhopf GF 2nd, Messer K, Jamieson C, Kipps TJ, Parker BA. A phase 1b study of zilovertamab in combination with paclitaxel for locally advanced/unresectable or metastatic Her2-negative breast cancer. Breast Cancer Res. 2024 Feb 26;26(1):32. doi: 10.1186/s13058-024-01782-0.

  PMID: 38408999 DERIVED

Related Links

• PubMed

MeSH Terms

Conditions

Breast Neoplasms

Interventions

cirmtuzumab; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Barbara Parker, MD
• Organization: University of California, San Diego

baparker@health.ucsd.edu

(858) 657-6100

Study Officials

• Barbara Parker, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor of Medicine

Study Record Dates

• First Submitted: May 16, 2016
• First Posted: May 18, 2016
• Study Start: August 15, 2018
• Primary Completion: July 13, 2021
• Study Completion: February 26, 2024
• Last Updated: August 7, 2025
• Results First Posted: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)