A Phase 1/2 Study to Investigate CRB-701 in Solid Tumors
- Registration Number
- NCT06265727
- Lead Sponsor
- Corbus Pharmaceuticals Inc.
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 348
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A Dose Escalation - CRB-701 Dose Level 1 CRB-701 CRB-701 Dose level 1, intravenous infusion over 30 mins, Dose schedule 1 Part A Dose Escalation - CRB-701 Dose Level 2 CRB-701 CRB-701 Dose Level 2, intravenous infusion over 30 mins, Dose schedule 1 Part A Dose Escalation - CRB-701 Dose Level 3 CRB-701 CRB-701 Dose Level 3, intravenous infusion over 30 mins, dose schedule 1 Part A Dose Escalation - CRB-701 Dose Level 4 CRB-701 CRB-701 Dose Level 4, intravenous infusion over 30 mins, dose schedule 1 Part B Dose Optimization: CRB-701 High dose CRB-701 Selected high dose of CRB-701, intravenous infusion over 30 mins, dose schedule 1 Part B Dose Optimization: CRB-701 low dose CRB-701 Selected Low dose of CRB-701, intravenous infusion over 30 mins Part C Dose Expansion - Cohort 1 CRB-701 Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1 Part C Dose Expansion - Cohort 1 Anti-PD-1 Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1 Part C Dose Expansion - Cohort 2 CRB-701 Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins Part C Dose Expansion - Cohort 3 CRB-701 Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1 Part C Dose Expansion - Cohort 3 Anti-PD-1 Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1 Part C Dose Expansion - Cohort 4 CRB-701 Recommended Phase 2 dose of CRB-701 and schedule, intravenous infusion over 30 mins Part C Dose Expansion - Cohort 5 CRB-701 Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1 Part C Dose Expansion - Cohort 5 Anti-PD-1 Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1 Part B Dose Optimization: CRB-701 high dose combined with anti-PD-1 CRB-701 Selected high dose of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1 Part B Dose Optimization: CRB-701 high dose combined with anti-PD-1 Anti-PD-1 Selected high dose of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1 Part B Dose Optimization: CRB-701 low dose combined with anti-PD-1 CRB-701 Selected low dose of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1 Part B Dose Optimization: CRB-701 low dose combined with anti-PD-1 Anti-PD-1 Selected low dose of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1 Part C Dose Expansion - Cohort 6 CRB-701 Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins Part C Dose Expansion - Cohort 7 CRB-701 Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1 Part C Dose Expansion - Cohort 7 Anti-PD-1 Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1
- Primary Outcome Measures
Name Time Method Part A: To confirm the safety and tolerability and determine MTD and PADR for CRB-701 21 days Occurrence of Dose Limiting Toxicities as defined in the protocol
Part B & C: To evaluate efficacy in terms of Objective Response Rate (ORR) Up to 6 months ORR is the percentage of participants that achieve a response (CR + PR) using RECIST 1.1
- Secondary Outcome Measures
Name Time Method Parts A, B, & C: To characterize the safety profile of CRB-701 Up to 6 months Numbers of treatment emergent adverse events with severity determined using NCI CTCAE v5.0 after single or multiple doses of CRB-701 or single and multiple doses of CRB-701 and an anti-PD-(L)1 therapy
Maximum observed plasma concentration of CRB-701 [total ADC] (Cmax) Approximately 9 weeks Maximum observed plasma concentration of total ADC after single and multiple doses
Maximum observed plasma concentration of free MMAE (Cmax) Approximately 9 weeks Maximum observed plasma concentration of free MMAE after single and multiple doses
Part B & C : To evaluate efficacy in terms of Disease Control Rate (DCR) Up to 6 months DCR is the sum of percentage of participants meeting the definition of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for at least 4 months using RECIST 1.1
Maximum observed plasma concentration of Total CRB-701 antibody [Tab] (Cmax) Approximately 9 weeks Maximum observed plasma concentration of free MMAE after single and multiple doses
Time to reach Cmax of Total CRB-701 [Total ADC] (Tmax) Approximately 9 weeks The amount of time to reach Cmax after single and multiple dose administration of CRB-701 (Total ADC)
Time to reach Cmax of free MMAE (Tmax) Approximately 9 weeks The amount of time to reach Cmax after single and multiple dose administration of free MMAE
Time to reach Cmax of Total CRB-701 antibody [Tab] (Tmax) Approximately 9 weeks The amount of time to reach Cmax after single and multiple dose administration of Tab
Time to reach Cmax of Total CRB-701 antibody [Tab] (Cmax) Approximately 9 weeks Maximum observed plasma concentration of free MMAE after single and multiple doses
Total Area Under the plasma concentration-time curve of Total CRB-701 [total ADC] (AUC) Approximately 9 weeks Maximum observed plasma concentration of free MMAE after single and multiple doses
Total Area Under the plasma concentration-time curve of free MMAE (AUC) Approximately 9 weeks Area under the plasma concentration versus time curve after single and multiple dose administration of free MMAE
Total Area Under the plasma concentration-time curve of Total CRB-701 antibody [Tab] (AUC) Approximately 9 weeks Area under the plasma concentration versus time curve after single and multiple dose administration of Tab
Trial Locations
- Locations (44)
O'Neal Comprehensive Cancer Center at University of Alabama-Birmingham
🇺🇸Birmingham, Alabama, United States
City of Hope Cancer Center
🇺🇸Duarte, California, United States
Moores Cancer Centre at UC San Diego Health
🇺🇸San Diego, California, United States
Helen Diller Family Comprehensive Cancer Center - UCSF
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Centres
🇺🇸Denver, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Florida Cancer Specialists
🇺🇸Orlando, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Hope and Healing Cancer Center
🇺🇸Hinsdale, Illinois, United States
Dana-Faber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Scroll for more (34 remaining)O'Neal Comprehensive Cancer Center at University of Alabama-Birmingham🇺🇸Birmingham, Alabama, United StatesRodney CarterContactclinical@corbuspharma.com