This study is a Phase 1/2, first-in-human, open-label, clinical trial to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of HMBD-501 in patients with advanced-stage, relapsed and/or refractory human epidermal growth factor receptor 3 (HER3)-expressing solid tumors. The study consists of 2 phases: a dose escalation phase (Phase 1) and a dose expansion phase (Phase 2). The primary objectives of Phase 1 are to characterize the overall safety and tolerability profile of increasing doses of HMBD-501 in patients with advanced-stage solid tumors and identify the recommended Phase 2 dose (RP2D) of ENV-501. During Phase 1, successive cohorts of patients will receive escalating doses of HMBD-501. The results of the dose escalation will determine the RP2D and dosing schedule of HMBD-501 to be administered in the Phase 2 part of the study. The primary objective of Phase 2 is to evaluate the preliminary clinical efficacy of HMBD-501 in dose expansion cohorts.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
180
ENV-501 is a HER3-targeted antibody-drug conjugate (ADC) with a humanized monoclonal antibody (mAb) conjugated with a chemotherapeutic payload via a linker.
Research Site
La Jolla, California, United States
RECRUITINGResearch Site
Indianapolis, Indiana, United States
RECRUITINGResearch Site
Farmington Hills, Michigan, United States
RECRUITINGResearch Site
Dallas, Texas, United States
RECRUITINGResearch Site
San Antonio, Texas, United States
RECRUITINGResearch Site
Campbelltown, New South Wales, Australia
WITHDRAWNResearch Site
Miranda, New South Wales, Australia
WITHDRAWNPhase 1 (Dose Escalation): Frequency of treatment-emergent adverse events
Time frame: through study completion, an average of 6 months
Phase 2 (Dose Expansion): Objective Response Rate (ORR)
Objective Response is defined as Complete Response (CR) or Partial Response (PR) by investigator assessment, measured by revised Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).
Time frame: through study completion, an average of 6 months
Phase 1 (Dose Escalation): Disease Control Rate (DCR)
DCR is defined as CR, PR, or Stable Disease (SD) by investigator assessment, measured by revised RECIST 1.1.
Time frame: through study completion, an average of 6 months
Phase 1 (Dose Escalation): Objective Response Rate (ORR)
Time frame: through study completion, an average of 6 months
Phase 1 (Dose Escalation): maximum blood concentration (Cmax) after a single dose
Time frame: At the end of Cycle 1 (each cycle is 21 days)
Phase 1 (Dose Escalation): time of maximum blood concentration (Tmax) after a single dose
Time frame: At the end of Cycle 1 (each cycle is 21 days)
Phase 1 (Dose Escalation): absorption to time t (AUC0-t) after a single dose
AUC represents "area under the concentration-time curve" and measures the amount of drug that is present in the blood from the time of administration to a given time 't'
Time frame: At the end of Cycle 1 (each cycle is 21 days)
Phase 1 (Dose Escalation): absorption to end of the dosing period (AUC0-tau) after a single dose
Time frame: At the end of Cycle 1 (each cycle is 21 days)
Phase 1 (Dose Escalation): total absorption (AUC0-infinity) after a single dose
Time frame: At the end of Cycle 1 (each cycle is 21 days)
Phase 1 (Dose Escalation): drug half-life (t1/2) after a single dose
Time frame: At the end of Cycle 1 (each cycle is 21 days)
Phase 1 (Dose Escalation): minimum blood concentration (Cmin) after a single dose
Time frame: At the end of Cycle 1 (each cycle is 21 days)
Phase 1 (Dose Escalation): rate of clearance (CL) after a single dose
Time frame: At the end of Cycle 1 (each cycle is 21 days)
Phase 1 (Dose Escalation): steady-state volume of distribution (Vss) after a single dose
Time frame: At the end of Cycle 1 (each cycle is 21 days)
Phase 1 (Dose Escalation): Cmax at steady state
Time frame: through study completion, an average of 6 months
Phase 1 (Dose Escalation): Tmax at steady state
Time frame: through study completion, an average of 6 months
Phase 1 (Dose Escalation): AUC0-t at steady state
Time frame: through study completion, an average of 6 months
Phase 1 (Dose Escalation):AUC0-tau at steady state
Time frame: through study completion, an average of 6 months
Phase 1 (Dose Escalation): t1/2 at steady state
Time frame: through study completion, an average of 6 months
Phase 1 (Dose Escalation): Cmin at steady state
Time frame: through study completion, an average of 6 months
Phase 1 (Dose Escalation): accumulation ratio at steady state
Time frame: through study completion, an average of 6 months
Phase 2 (Dose Expansion): Disease Control Rate (DCR)
Time frame: through study completion, an average of 6 months
Phase 2 (Dose Expansion): Duration of Response (DoR)
A DoR event is defined as disease progression or death due to any cause in the subset of patients who achieved CR or PR on the study. DoR will be calculated from the date of first radiographic evidence of objective response by RECIST v1.1 to the date of progression, date of death, or date of last follow-up, whichever is the earliest.
Time frame: through study completion, an average of 6 months
Phase 2 (Dose Expansion): Progression-free Survival (PFS)
A PFS event is defined as disease progression or death due to any cause. PFS will be calculated from the date of treatment start to the date of progression, date of death, or date of last follow-up, whichever is the earliest.
Time frame: through study completion, an average of 6 months
Phase 2 (Dose Expansion): Frequency of treatment-emergent adverse events
Time frame: through study completion, an average of 6 months
Phase 2 (Dose Expansion): Cmax at steady state
Time frame: through study completion, an average of 6 months
Phase 2 (Dose Expansion): Cmin at steady state
Time frame: through study completion, an average of 6 months
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