A Study of the Intra-Patient Escalation Dosing Regimen With IMCgp100 in Patients With Advanced Uveal Melanoma

Official Title

A Phase I/II Open-label, Multi-centre Study of the Safety and Efficacy of IMCgp100 Using the Intra-patient Escalation Dosing Regimen in Patients With Advanced Uveal Melanoma

Summary:

IMCgp100-102 is a Phase I study of the weekly intra-patient escalation dose regimen with IMCgp100 as a single agent in patients with metastatic uveal melanoma (mUM). According to this regimen, all patients in the trial will receive 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW) and then a dose escalation will commence at the third weekly dose at C1D15. The Phase I testing of the intra-patient escalation dosing regimen is designed to achieve a higher exposure and maximal plasma concentration of IMCgp100 after doses at Cycle 1 Day 15 (C1D15) and thereafter .

Trial Description

Primary Outcome:

  • Phase 1 Recommended phase 2 dose of the intra-patient escalation regimen (RP2D-IE)
  • 2. Phase 2: Objective response rate by RECIST 1.1 assessed by independent central review
Secondary Outcome:
  • Objective response rate (Phase 1)
  • Progression free survival
  • Overall survival
  • Duration of response
  • Time to response
  • Minor response rate
  • Number of treatment dose interruptions and reductions
  • Area under the plasma concentration-time curve (AUC)
  • Area under the plasma concentration-time curve (AUC)
  • The maximum observed plasma drug concentration after single dose administration (Cmax)
  • The time to reach maximum plasma concentration (Tmax)
  • The elimination half-life (t1/2)
  • Incidence of anti-IMCgp100 antibody formation
This is a Phase I clinical study of IMCgp100 in patients with advanced melanoma. In the Phase I FIH study of IMCgp100 in advanced melanoma, a dose escalation was conducted with IMCgp100 administered on a weekly basis (Middleton, 2015). In this study, the MTD when IMCgp100 is administered on a weekly basis was declared at 600 ng/kg. With a data cut off of 18 August 2015, it was observed that DLT of grade 3 (n=3) and grade 4 (n=1) hypotension in the weekly dosing cohort was observed with the first dose in this trial. Based on observed safety and the PK profile, a flat dosing regimen was implemented across the program and the RP2D of the RP2D-QW was identified as 50 mcg QW. In this same FIH study, several patients with metastatic uveal melanoma were treated in the weekly dosing regimen at the MTD dose level (600 ng/kg) and as well at the dose level above MTD, 900 ng/kg (n=5, data cut off 18 August 2015). Based on review of the observed objective responses in the Phase I trial in UM as well as objective responses noted in cutaneous melanoma, it was noted that patients with larger diameters of disease burden (both cutaneous and UM) experienced objective tumour responses at the higher overall exposures to IMCgp100. The intra-patient dose escalation study design is based on 2 observations in the clinic: (1) objective partial and minor tumour responses in patients with higher tumour burdens were generally observed at the higher absolute doses in the Phase I trial and (2) the occurrences of more severe toxicity leading to dose limitation were limited to the first 2 weeks of dosing on C1D1 and C1D8. Based on these 2 observations, it is hypothesized that an increased exposure to drug in the weeks following the occurrence of the more severe toxicity (at the first 2 doses) may lead to an enhanced tumour response in a setting of an unfavorable tumour microenvironment such as UM. This is a Phase I study of IMCgp100 administered on a weekly basis with an intra-patient escalation dosing regimen. The intra-patient escalation occurs at the third weekly dose on Cycle 1 Day 15 (C1D15). According to this regimen, all patients in the trial will receive 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW) and then a dose escalation will commence at the third weekly dose at C1D15 with the goal to achieve a long-term dosing regimen at a dose higher than that identified for the straight weekly dosing regimen (RP2D-QW). The dose escalation will identify the RP2D-IE. The Phase I portion of the study will be a standard 3+3 dose escalation design. After the dose escalation portion is complete and the recommended Phase II dose of the intra-patient escalation dose regimen (RP2D-IE) is identified, 2 expansion cohorts in metastatic uveal melanoma will be completed. The cohorts will enroll patients with metastatic uveal melanoma and are defined based on prior therapy The expansion portion will enroll approximately 150 patients.

View this trial on ClinicalTrials.gov

Interested in this trial?

Print this page and take it to your doctor to discuss your eligibilty and treatment options. Only your doctor can refer you to a clinical trial.

Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society