Overview
The goal of this clinical trial is to define a safe and effective dose of CRB-701 for participants with solid tumors that are expressing a protein called nectin-4.
The main questions it aims to answer are:
What is the the safe and effective dose of CRB-701 when used alone? What cancers can be treated effectively with CRB-701?
Participants will be asked to attend clinic and be given a intravenous infusion of CRB-701 on its own. They will have blood tests and other assessments to measure whether CRB-701 will have CT or MRI scans to measure the effect on tumors.
Description
This is a three-part open-label, Phase 1/2 clinical trial designed to evaluate the safety, PK, and efficacy of CRB-701 in participants with advanced solid tumors expressing nectin-4.
Part A will include solid tumor types known to express nectin-4. Dose escalation will be guided by the Bayesian optimal interval (BOIN) design to determine the MTD of CRB-701. Four (4) dose groups are pre-determined. Dose escalation/de-escalation decisions are made based on the occurrence of DLT.
Part B will determine the RP2D of CRB-701 by evaluating two dose levels of CRB-701 alone and in combination with anti-PD-1 by using a time-to-event Bayesian optimal Phase 2 (TOP) study design to optimize the dose of CRB-701 in one or more separate cohorts of participants with nectin-4-positive tumors.
During Part C, the RP2D dose of CRB-701 alone or combined with anti-PD-1 will be evaluated in five planned expansion cohorts using Simon's optimal two-stage design.
Eligibility
Inclusion Criteria:
- Confirmed diagnosis of select advanced or metastatic nectin-4 expressing solid tumors that have progressed following at least one line of therapy or have no other standard therapy with proven clinical benefit.
Exclusion Criteria:
- Active of uncontrolled CNS metastases
- History of solid tumors other than the diseases under study
- History of and/or current cardiovascular events or conditions in the previous 6 months
- Pre-existing >/= Grade 2 neuropathy
- Hemoglobin A1C (HbA1C) >/= 8%, uncontrolled diabetes mellitus or know diabetic neuropathy
- Active ocular disease at baseline
- Chronic severe liver disease or live cirrhosis
- Interstitial lung disease or pneumonitis within 6 months on initiating treatment on study
- Other significant cormorbidities.