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Published on: July 25, 2020
A phase II study of the bispecific antibody MDX-H210 (anti-HER2 x CD64) with GM-CSF in HER2+ advanced prostate cancer
N D James1, P J Atherton, J Jones
1CRC Institute for Cancer Studies, University of Birmingham, Birmingham, B15 2TA, UK.
Abstract:
The proto-oncogene HER2 presents a novel therapeutic target. We report results in 25 patients with HER2+ advanced prostate cancer treated with the bispecific antibody MDX-H210 15 microg m(-2)by intravenous infusion plus GM-CSF 5 microg kg(-1)day(-1)by subcutaneous injection for 4 days repeated weekly for 6 weeks. Patients with stable disease or better received further cycles of treatment until disease progression or study withdrawal. 1 patient received no treatment and 4 received less than 1 cycle and are included in the toxicity analysis only. Median duration of follow up was 105+ (range 21-188) days. Toxicity was generally NCI-CTG 0-2. There were 2 grade 4 adverse events (heart failure and dyspnoea) and 1 grade 3 event (allergic reaction) resulting in discontinuation of the study medication. There were 9 further grade 3 events not resulting in trial withdrawal. There were no treatment-related deaths. 7/20 (35%) evaluable patients had a >50% PSA response of median duration 128 (range 71-184+) days. 7/12 (58%) patients with evaluable pain had improvements in pain scores. The PSA relative velocity on therapy decreased in 15/18 (83%) assessable patients compared to pre-study. GM-CSF and MDX-H210 is active in hormone refractory prostate carcinoma with acceptable toxicity; further studies are warranted.
Insights
This study shows that the bispecific antibody MDX-H210 combined with GM-CSF is effective in treating advanced prostate cancer. The treatment demonstrated acceptable toxicity and positive responses in patients with HER2-positive tumors.
Area of Science:
- Oncology
- Immunotherapy
- Prostate Cancer Research
Background:
- The HER2 proto-oncogene is a potential therapeutic target in cancer.
- Advanced prostate cancer, particularly hormone-refractory forms, requires novel treatment strategies.
Purpose of the Study:
- To evaluate the efficacy and toxicity of the bispecific antibody MDX-H210 combined with GM-CSF in patients with HER2-positive advanced prostate cancer.
- To assess treatment response based on prostate-specific antigen (PSA) levels, pain scores, and PSA velocity.
Main Methods:
- A phase I/II study involving 25 patients with HER2-positive advanced prostate cancer.
- Treatment consisted of MDX-H210 (15 microg m(-2) IV) plus GM-CSF (5 microg kg(-1) SC) for 4 days weekly for 6 weeks, with further cycles for stable disease or better.
- Toxicity was assessed using NCI-CTG criteria. Efficacy was measured by PSA response, pain score improvement, and PSA relative velocity.
Main Results:
- 35% (7/20) of evaluable patients achieved a >50% PSA response, with a median duration of 128 days.
- 58% (7/12) of patients with evaluable pain reported improvements.
- PSA relative velocity decreased in 83% (15/18) of assessable patients.
- Toxicity was generally mild (NCI-CTG 0-2), with 2 grade 4 and 10 grade 3 adverse events reported, leading to discontinuation in one case. No treatment-related deaths occurred.
Conclusions:
- The combination of GM-CSF and MDX-H210 demonstrates activity in hormone-refractory prostate cancer.
- The treatment regimen shows acceptable toxicity profiles.
- Further clinical studies are warranted to explore the potential of this therapeutic approach in advanced prostate cancer.
