A Phase I/II, Open-Label, Multicenter Study of ALE.P02 (Claudin-1 Targeted Antibody-Drug Conjugate) as a Monotherapy in Adult Patients With Selected Advanced or Metastatic CLDN1+Squamous Solid Tumors
Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, preliminary anti-tumor activity, and to determine the recommended Phase II dose (RP2D) of the ALE.P02 monotherapy in adult patients with selected squamous solid tumors.
Detailed description
This Study has a Phase I ALE.P02 monotherapy dose escalation and recommended dose for expansion (RDE) study and a Phase II study of ALE.P02 as monotherapy at RP2D in adult patients with selected advanced or metastatic Claudin-1 positive (CLDN1+) cancers.
Arms & interventions
- DrugALE.P02
ALE.P02, will be administered by IV infusion according to the assigned arms.
Outcome measures
Primary
Number of Patients with Dose Limiting Toxicities (DLTs)
DLTs as defines in the protocol will be assessed to evaluate safety and tolerability of ALE.P02 (Phase I Dose Escalation), and to establish RP2D for ALE.P02 (Phase I RDE).
Time frame: Up to 28 days
Number of Patients with Adverse Events
Adverse events will be assessed to evaluate safety and tolerability of ALE.P02 (Phase I Dose Escalation), and to establish RP2D for ALE.P02 (Phase I RDE).
Time frame: Screening (day -28 to day -1) up to Safety follow-up (30 ± 5 days post last dose [Up to 3.5 years])
Overall Response Rate (ORR) (Phase I)
The ORR is the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1.) This is assessed to establish RP2D for ALE.P02 (Phase I RDE)
Time frame: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)
Duration of Response (DoR) (Phase I)
The DoR is defined for patients achieving a confirmed CR or PR as the time from the initial response of CR or PR per Investigator review according to RECIST 1.1 to disease progression or death of any cause, whichever occurs earlier. This is assessed to establish RP2D for ALE.P02 (Phase I RDE).
Time frame: From ALE.P02 treatment initiation until disease progression or study completion (Up to 3.5 years)
Overall Response Rate (ORR) (Phase II)
The ORR is assessed to assess anti-tumor activity of ALE.P02 (Phase II).
Time frame: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)
Duration of Response (DoR) (Phase II)
The DoR is assessed to assess anti-tumor activity of ALE.P02 (Phase II).
Time frame: From ALE.P02 treatment initiation until disease progression or study completion (Up to 3.5 years)
Secondary
Disease control rate (DCR) (Phase I and II)
Time frame: From ALE.P02 treatment initiation until at or prior to initiation of the use of new anti-cancer therapy (Up to 3.5 years)
Median Progression-Free Survival (PFS) at 6 and 12 Months (Phase I and II)
Time frame: At 6 and 12 months after initiation of ALE.P02 treatment
Median Overall Survival (OS) at 6, 12, and 24 Months (Phase I and II)
Time frame: At 6, 12, and 24 months after initiation of ALE.P02 treatment
Blood Concentration of ALE.P02 Antibody-drug Conjugate (ADC)
Time frame: Phase I and II: Cycle 1 Day 1 until at end of treatment visit (EoT) (Up to 3.5 years)
Blood Concentration of Total Antibody
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Blood Concentrations of Payload
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Area under the concentration-time curve over the dosing interval (AUCtau)
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Area under the concentration-time curve from pre-dose (time 0) to the time of the last quantifiable concentration (AUClast)
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time (AUCinf)
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Maximum Concentration (Cmax)
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Minimum concentration (Cmin)
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Concentration at the end of a Dosing Interval (Ctrough)
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
The terminal elimination rate constant (KeL)
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Terminal elimination half-life (t½)
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Time of Maximum Concentration (tmax)
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Average Concentration (Cavg)
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Number of Patients with Presence of anti-ALE.P02 Antibodies
Time frame: Phase I and II: Cycle 1 Day 1 until at EoT (Up to 3.5 years)
Eligibility criteria
Study locations (8)
Mayo Foundation for Medical Education and Research - Mayo Cl
Scottsdale, Arizona, 85259
Providence Medical Foundation
Fullerton, California, 92835
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Yale Comprehensive Cancer Center
New Haven, Connecticut, 06510
The University of Chicago Medical Center - Oncology
Chicago, Illinois, 60637
Norton Cancer Institue Downtown
Louisville, Kentucky, 40202
Hackensack University Medical Center
Hackensack, New Jersey, 07601
NEXT Oncology Virginia
Fairfax, Virginia, 22031