A first-in-human (FIH) phase I/II, dose escalation, pharmacokinetic (PK) study to assess the safety and tolerability of VAL-201 in patients with advanced prostate cancer (APC) and other advanced solid tumours

Background

Most patients with advanced prostate cancer treated with androgen deprivation therapy experience side effects of castration and eventually relapse. VAL-201 is a synthetic decapeptide that inhibits interaction of the androgen and oestradiol receptors with Src tyrosine kinase, disrupting steroid or epithelial growth factor dependent DNA synthesis. The aims of this FIH study are to assess safety, tolerability, PK and activity of VAL-201 in patients with APC.

Methods

An accelerated titration, open label, dose-escalating design has been used to identify a maximum tolerated/administered dose (MTD/MAD). VAL-201 is given subcutaneously on Days 1, 8, 15, q21. The starting dose was 0.5 mg/kg. Expansion to a 3 + 3 design was planned to occur at dose level (DL) 3. Dose limiting toxicity (DLT) was assessed during Cycle 1 and safety evaluations were conducted weekly.

Results

Eight patients have been recruited to 4 DLs (0.5mg/kg n = 1; 1.0mg/kg n = 1; 2.0mg/kg n = 3; 4.0mg/kg n = 3). Patient demographics are in Table 1. The final planned escalation will be 5.0mg/kg, the maximum feasible single dose which may be administered. No DLT has occurred to date. The only drug-related adverse event (AE) observed has been Grade 1 injection site reaction. Median duration on trial is currently 85 days. Early signs of clinical activity have been observed with prolonged PSA doubling time (n = 2), stabilisation of PSA (n = 1) and >50% decrease in PSA (n = 1, Table).

*continues on study **minimum of three months

Conclusions

VAL-201 is very well-tolerated with early signs of clinical activity in advanced prostate cancer. No DLT has been observed. The MTD/MAD has not yet been identified and the study continues. Expansion to other tumour types is planned. PK data analysis is ongoing and will be presented.

Clinical trial identification

NCT02280317

Legal entity responsible for the study

N/A

Funding

ValiRx, Inc

Disclosure

A. Boyd: Is employed as a Consultant by ValiRx as a medical monitor for the trial. G. Morris: Employee of ValiRx.All other authors have declared no conflicts of interest.