Study of Docetaxel Combined with Cirmtuzumab in Metastatic Castration Resistant Prostate Cancer

A Phase 1b Trial Investigating Docetaxel Combined with Cirmtuzumab in Patients with Metastatic Castration Resistant Prostate Cancer

The purpose of this study is to examine the safety and efficacy of cirmtuzumab in combination with standard of care docetaxel in patients with metastatic castration resistant prostate cancer. Docetaxel is a taxane chemotherapy which has been shown to prolong survival in men with castration resistant prostate cancer. Cirmtuzumab is a monoclonal antibody that targets the receptor called ROR1 of the non-canonical Wnt pathway and is suspected to contribute to prostate cancer growth and progression.

This study seeks to targeting the non-canonical Wnt pathway with an antibody against ROR1. ROR1 is an attractive target given its low expression in non-malignant tissues and its role in proliferation and survival in prostate cancer. From preclinical data in a variety of tumor types, blockade of ROR1 inhibits cell growth and cirmtuzumab has shown efficacy in clinical trials with CLL. Preclinical data suggests that ROR1 is upregulated in chemotherapy resistant cells and treatment with cirmtuzumab and a taxane achieved higher cytotoxic response than both agents alone, supporting the use of the combination of cirmtuzumab and a taxane. Based on the biological rationale behind cirmtuzumab and preclinical activity with docetaxel, this is an open label, phase 2 clinical trial to evaluate the safety and efficacy of cirmtuzumab in combination with docetaxel for the treatment of metastatic, castrate resistant prostate adenocarcinoma.

Inclusion Criteria:

1. Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate. Patients with neuroendocrine component are eligible.
2. Participants must have castrate levels of serum testosterone < 50 ng/dL.
3. Participants without orchiectomy must be maintained on luteinizing hormone releasing hormone (LHRH) agonist/antagonist.
4. Participants must have received prior abiraterone and/or next generation androgen receptor antagonist (enzalutamide, apalutamide, or darolutamide) for hormone sensitive disease or CRPC. Prior docetaxel for hormone sensitive disease is permitted.
5. Participants must have progressive disease. Patients with non-measurable disease are eligible.
6. Eastern Cooperative Oncology Group performance status ≤1 (Karnofsky ≥80%).
7. Patients must have normal organ and marrow function.

Exclusion Criteria:

1. No pure small cell carcinoma.
2. Prior treatment with cirmtuzumab.
3. No prior treatment with docetaxel for CRPC.
4. Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment initiation. Treatment with cytotoxic chemotherapy within 3 weeks of treatment initiation. Treatment enzalutamide or other investigational prostate cancer directed therapy within 4 weeks of treatment initiation.
5. Palliative radiation therapy to the bone or other sites within 2 weeks of treatment initiation.
6. Imminent or established spinal cord compression based on clinical and/or imaging findings.
7. Known active central nervous system metastases and/or carcinomatous meningitis.
8. Uncontrolled intercurrent illness or clinically significant medical condition.
9. Treatment with antimicrobial agent within 4 weeks of treatment initiation.