Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Supportive and palliative care

937 - First in human study of RPH-203, a new potent RANKL blocker, for the treatment of bone metastasis


20 Dec 2015


Supportive and palliative care


Shorena Archuadze


Annals of Oncology (2015) 26 (suppl_9): 111-124. 10.1093/annonc/mdv531


S. Archuadze1, S. Grishin1, D. Koloda1, G. Konopleva1, M. Samsonov1, Y. Lavrovsky2, J. Lickliter3

Author affiliations

  • 1 Medical Department, CJSC "R-Pharm", 123317 - Moscow/RU
  • 2 Research And Development, R-Pharm Overseas Inc., 92130 - San Diego/US
  • 3 Clinical Trial Unit, Nucleus Network, 3004 - Melbourne/AU


Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 937


Bone metastasis is a common complication of solid tumors. The receptor activator of nuclear factor-kB ligand (RANKL) pathway is the key mechanism of bone destruction by metastatic tumors. RPH-203 is an innovative biotechnology drug being developed for the treatment of bone metastasis. Successful completion of preclinical studies enabled conduct of the first-in-human Phase I study.


A randomized, double-blind, placebo-controlled study to evaluate the safety and pharmacokinetics (PK) of RPH-203 after single ascending subcutaneous (SC) doses of 10, 30, 40 or 60 mg or placebo was conducted in 32 healthy male volunteers. Non-compartmental methods were used to determine PK values (AUCt, AUCinf, Cmax, Tmax, &lgr;z, t½, CL and Vd). Pharmacodynamic (PD) values included procollagen Type I N-terminal peptide - P1NP, serum C-telopeptide 1 – sCTX, urine N-telopeptide - uNTX. Safety variables (adverse events (AE), vital signs, electrocardiography (ECG), laboratory findings) were assessed by dose.


RPH-203 exposure (Cmax, AUC) increased greater than dose-proportional with dose. Mean T1/2 was 161 hours (71 - 301 h) and median Tmax was 16 hours (10 - 144 h) with consistency across the dose range. Serum CTX showed rapid dose-dependent decrease to nadir (Day 3 for 10 mg, Day 7 for 30–60 mg doses). Single SC injection of RPH-203 at 10 mg, 30 mg, 40 mg and 60 mg resulted in 16%, 54%, 84% and 83% decrease in mean sCTX levels, respectively. Urine NTX decreased by 67%, 77% and 75% to nadir by Day 7 in 30 mg, 40 mg and 60 mg dose groups, respectively. The reduction in sCTX and uNTX levels was not seen in volunteers receiving placebo. There were no clear differences in safety profiles between subjects treated with RPH-203 or placebo and between dose levels, except for pyrexia in 2 subjects receiving 60 mg of RPH-203 that was considered as dose limiting toxicity (DLT) though non-serious AE. The only common AE (>10%) was headache in 50% (12/24) and in 25% (2/8) of subjects, who received RPH-203 or placebo, respectively.


RPH-203 was well tolerated up to 40 mg. RPH-203 dose increase from 40 mg to 60 mg lead to a DLT occurrence. RPH-203 SC injection at 40 mg is a recommended dose for further development with acceptable risk/benefit profile.

Clinical trial identification

ID: ACTRN12613000651785; clinical trial protocol: RPH203-CLIN-001


All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings