medwireNews: DSTP3086S, a humanized immunoglobulin G1 monoclonal antibody that targets six-transmembrane epithelial antigen of the prostate 1 (STEAP1) has shown promising results in a phase 1 study of metastatic castration-resistant prostate cancer (mCRPC).
“DSTP3086S demonstrated an acceptable safety proﬁle, with evidence of antitumor activity conﬁrming that the targeting of STEAP1-expressing mCRPC tumors with an ADC [antibody–drug conjugate] is feasible,” report Daniel Danila (Memorial Sloan Kettering Cancer Center, New York, USA) and colleagues in the Journal of Clinical Oncology.
The researchers conducted a dose-escalation study in which 77 participants received intravenous DSTP3086S 0.3–2.8 mg/kg once every 3 weeks. This was followed by a dose expansion to DSTP3086S 0.8 mg/kg or 1.0 mg/kg every week in four and three patients, respectively.
Overall, 90.0% of participants experienced an adverse event, with grade 3 or 4 events in 31%. The most common treatment-related adverse events in those given DSTP3086S every 3 weeks were fatigue (56%), peripheral neuropathy (51%), nausea (38%), constipation (35%), decreased appetite (34%), diarrhea (26%), and vomiting (25%). In those treated weekly, one patient given 1.0 mg/kg DSTP3086S developed grade 3 hyperglycemia and grade 4 hypophosphatemia, which were considered to be dose-limiting events.
Eleven (14%) men in the every-3-week dosing group had a confirmed prostate-specific antigen (PSA) reduction of at least 50%, meeting the criteria for response. And of 46 patients with evaluable disease per RECIST at baseline, two (4%) experienced a partial response and 24 (52%) had stable disease.
Most of the study participants had STEAP1-expressing tumors, with immunohistochemistry (IHC) 1+ in 26%, IHC 2+ in 49%, and IHC 3+ in 24%. Of the 11 men who experienced a PSA response, one (10%) had IHC 1+, ﬁve (45%) had IHC 2+, and ﬁve (45%) had IHC 3+ tumors.
And of 38 patients in the every-3-weeks dosing group who had circulating tumor cells (CTCs) of at least 5/7.5 mL of blood at baseline, 19 (50%) had levels below this following treatment, as did 16 (59%) of 27 men who received DSTP3086S at doses higher than 2 mg/kg.
Commenting on this, the researchers note: “Although PSA declines and imaging responses with STEAP1-ADC treatment were not common, half of the patients with evaluable CTCs had CTC conversions, some coupled with prolonged disease stability.
“This suggests activity for STEAP1-ADC that is reﬂected by CTC conversion rather than by PSA or imaging responses and warrants further investigation.”
They conclude: “Although DSTP3086S would require optimization for further clinical development, these data may inform development of novel ADCs, chimeric antigen receptor T cells, and immune cell-recruiting bispeciﬁc antibodies that target STEAP1.”
By Catherine Booth
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