Pembro and HER2Bi-Armed Activated T Cells in Treating Patients With Metastatic Castration Resistant Prostate Cancer

NCT03406858 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 2015-135NCI-2017-02156P30CA022453
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well pembrolizumab and HER2Bi-armed activated T cells work in treating patients with castration resistant prostate cancer that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. HER2Bi-armed activated T cells are made using T cells and may target and kill cancer cells. Giving pembrolizumab and HER2Bi-armed activated T cells may work better in treating patients with castration resistant prostate cancer.

Conditions

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Percentage of patients achieving clinical progression-free interval at 6 months from study registration

  Up to 6 months

Study Arms (1)

Treatment (pembrolizumab, HER2Bi-armed activated T cells)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes every 3 weeks. Treatment repeats every 3 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity. Beginning at least 1 week after pembrolizumab, patients receive HER2Bi-armed activated T cells IV over 5-15 minutes 2 times a week for 4 weeks in the absence of disease progression or unacceptable toxicity.

Biological: HER2Bi-Armed Activated T Cells; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

HER2Bi-Armed Activated T Cells BIOLOGICAL

Given IV

Also known as: Anti-CD3 x Anti-Her2/neu Bispecific Antibody-Armed Activated T Cells, HER2Bi-Armed ATCs

Treatment (pembrolizumab, HER2Bi-armed activated T cells)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, HER2Bi-armed activated T cells)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, HER2Bi-armed activated T cells)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial
• Have histologically confirmed prostate adenocarcinoma, with metastases
• Progression by either PSA, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for measurable disease or new areas of metastases on bone scan or symptom progression related to prostate cancer despite castrate levels of testosterone; (level \< 50 ng/ml)
• Be agreeable to continue to maintain castrate levels of testosterone
• At least 2 weeks should have elapsed since any immunosuppressive therapy
• At least 4 weeks since prior chemotherapy for metastatic disease or at least 2 weeks since prior androgen targeting agents such as ketoconazole, abiraterone, enzalutamide, etc.
• Discontinue anti-androgens prior to therapy; at least 6 weeks since last dose of bicalutamide or nilutamide and at least 4 weeks from last dose of flutamide
• Have normal bone marrow, renal and hepatic function as deemed by the treating physician and approved by the clinical principal investigator (PI) Dr. Vaishampayan
• Not have concurrent anti-cancer therapy
• Not have concurrent immunosuppressive therapy or medical condition likely to cause immunosuppression
• Have life expectancy \> 6 months
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)/Zubrod performance scale
• Agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Within 10 days of treatment registration: Absolute neutrophil count (ANC) \>= 1,500 /mcL

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (\> 10 mg of prednisone daily or equivalent steroid doses) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
• Has a known history of active TB (Bacillus tuberculosis)
• Has hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or has not recovered (i.e. =\< grade 1 or at baseline) from adverse events due to agents administered earlier; Note: Subjects with =\<grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Has received major surgery, subject must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject?s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Interventions

pembrolizumab

Limitations and Caveats

Due to COVID-19 pandemic, cellular therapies were suspended and hence the study was discontinued before the targeted enrollment was reached.

Results Point of Contact

• Title: Dr. Abhinav Deol
• Organization: Wayne State University/Karmanos Cancer Institute

deola@karmanos.org

313-576-8093

Study Officials

• Abhinav Deol, M.D.

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 8, 2017
• First Posted: January 23, 2018
• Study Start: June 7, 2018
• Primary Completion: January 20, 2021
• Study Completion: November 7, 2022
• Last Updated: May 3, 2023
• Results First Posted: November 15, 2022

Record last verified: 2023-04

Locations

US (1)