A Phase 1/2 Study to Investigate CRB-701 in Solid Tumors

April 8, 2024 updated by: Corbus Pharmaceuticals Inc.

A Phase 1/2 Study to Investigate the Safety, Pharmacokinetics, and Efficacy of CRB-701, an Antibody-drug Conjugate Targeting Nectin-4, in Patients With Advanced Solid Tumors

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 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 will be evaluated in five planned expansion cohorts using Simon's optimal two-stage design.

Study Type

Interventional

Enrollment (Estimated)

420

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Spain
      • Barcelona, Spain, 08023
      • Barcelona, Spain, 08035
      • Madrid, Spain, 28040
      • Valencia, Spain, 46010
  • Turkey
      • Adana, Turkey, 83114
        • Not yet recruiting
        • Adana Numune Egitim ve Arastirma Hastanesi (Adana City Education and Research Hospital)
        • Contact:
      • Ankara, Turkey
      • Ankara, Turkey
      • Istanbul, Turkey, 34720
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
      • Cambridge, United Kingdom, CB2 0QQ
      • Cardiff, United Kingdom, CF15 7QZ
      • Leeds, United Kingdom, LS9 7LP
      • London, United Kingdom, SE1 9RT
      • London, United Kingdom, W12 0NN
      • Manchester, United Kingdom, M20 4BX
      • Southampton, United Kingdom, SO16 6YD
      • Wirral, United Kingdom, CH63 4JY
        • Not yet recruiting
        • University of Liverpool - Clatterbridge Medical Centre
        • Contact:
  • United States
    • California
      • San Diego, California, United States, 92037
      • San Francisco, California, United States, 94115
        • Not yet recruiting
        • Helen Diller Family Comprehensive Cancer Center - UCSF
        • Contact:
    • Colorado
      • Denver, Colorado, United States, 80218
    • Connecticut
      • New Haven, Connecticut, United States, 06510
    • Florida
      • Orlando, Florida, United States, 32806
    • Illinois
      • Chicago, Illinois, United States, 60637
      • Hinsdale, Illinois, United States, 60521
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Not yet recruiting
        • Dana-Faber Cancer Institute
        • Contact:
          • Rodney Carter
    • Nebraska
      • Lincoln, Nebraska, United States, 68506
    • North Carolina
      • Huntersville, North Carolina, United States, 28078
    • Texas
      • Tyler, Texas, United States, 75702
    • Virginia
      • Fairfax, Virginia, United States, 22031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A Dose Escalation - CRB-701 Dose Level 1
CRB-701 Dose level 1, intravenous infusion over 30 mins, Dose schedule 1
Drug: CRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)
Experimental: Part A Dose Escalation - CRB-701 Dose Level 2
CRB-701 Dose Level 2, intravenous infusion over 30 mins, Dose schedule 1
Drug: CRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)
Experimental: Part A Dose Escalation - CRB-701 Dose Level 3
CRB-701 Dose Level 3, intravenous infusion over 30 mins, dose schedule 1
Drug: CRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)
Experimental: Part A Dose Escalation - CRB-701 Dose Level 4
CRB-701 Dose Level 4, intravenous infusion over 30 mins, dose schedule 1
Drug: CRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)
Experimental: Part B Dose Optimization: CRB-701 High dose
Selected high dose of CRB-701, intravenous infusion over 30 mins, dose schedule 1
Drug: CRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)
Experimental: Part B Dose Optimization: CRB-701 low dose
Selected Low dose of CRB-701, intravenous infusion over 30 mins, once every three weeks
Drug: CRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)
Experimental: Part C Dose Expansion - Cohort 1
Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins
Drug: CRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)
Experimental: Part C Dose Expansion - Cohort 2
Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins
Drug: CRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)
Experimental: Part C Dose Expansion - Cohort 3
Recommended Phase 2 dose of CRB-701 and schedule, intravenous infusion over 30 mins
Drug: CRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)
Experimental: Part C Dose Expansion - Cohort 4
Recommended Phase 2 dose of CRB-701 and schedule, intravenous infusion over 30 mins
Drug: CRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)
Experimental: Part C Dose Expansion - Cohort 5
Recommended Phase 2 dose of CRB-701 and schedule, intravenous infusion over 30 mins
Drug: CRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A: To confirm the safety and tolerability and determine MTD and PADR for CRB-701
Time Frame: 21 days
Occurrence of Dose Limiting Toxicities as defined in the protocol
21 days
Part B & C : To evaluate efficacy in terms of Disease Control Rate (DCR)
Time Frame: 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
Up to 6 months
Part B & C: To evaluate efficacy in terms of Objective Response Rate (ORR)
Time Frame: Up to 6 months
ORR is the percentage of participants that achieve a response (CR + PR) using RECIST 1.1
Up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum observed plasma concentration of CRB-701 [total ADC] (Cmax)
Time Frame: Approximately 9 weeks
Maximum observed plasma concentration of total ADC after single and multiple doses
Approximately 9 weeks
Maximum observed plasma concentration of free MMAE (Cmax)
Time Frame: Approximately 9 weeks
Maximum observed plasma concentration of free MMAE after single and multiple doses
Approximately 9 weeks
Maximum observed plasma concentration of Total CRB-701 antibody [Tab] (Cmax)
Time Frame: Approximately 9 weeks
Maximum observed plasma concentration of free MMAE after single and multiple doses
Approximately 9 weeks
Time to reach Cmax of Total CRB-701 [Total ADC] (Tmax)
Time Frame: Approximately 9 weeks
The amount of time to reach Cmax after single and multiple dose administration of CRB-701 (Total ADC)
Approximately 9 weeks
Time to reach Cmax of free MMAE (Tmax)
Time Frame: Approximately 9 weeks
The amount of time to reach Cmax after single and multiple dose administration of free MMAE
Approximately 9 weeks
Time to reach Cmax of Total CRB-701 antibody [Tab] (Tmax)
Time Frame: Approximately 9 weeks
The amount of time to reach Cmax after single and multiple dose administration of Tab
Approximately 9 weeks
Time to reach Cmax of Total CRB-701 antibody [Tab] (Cmax)
Time Frame: Approximately 9 weeks
Maximum observed plasma concentration of free MMAE after single and multiple doses
Approximately 9 weeks
Total Area Under the plasma concentration-time curve of Total CRB-701 [total ADC] (AUC)
Time Frame: Approximately 9 weeks
Maximum observed plasma concentration of free MMAE after single and multiple doses
Approximately 9 weeks
Total Area Under the plasma concentration-time curve of free MMAE (AUC)
Time Frame: Approximately 9 weeks
Area under the plasma concentration versus time curve after single and multiple dose administration of free MMAE
Approximately 9 weeks
Total Area Under the plasma concentration-time curve of Total CRB-701 antibody [Tab] (AUC)
Time Frame: Approximately 9 weeks
Area under the plasma concentration versus time curve after single and multiple dose administration of Tab
Approximately 9 weeks
Parts A, B, % C: To characterize the safety profile of CRB-701
Time Frame: 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
Up to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Corbus Pharmaceuticals Inc.

Collaborators

CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.

Investigators

  • Principal Investigator: Ari Rosenberg, MD, University of Chicago
  • Principal Investigator: David Pinato, MD, Imperial College London
  • Study Director: Ian Hodgson, PhD, Corbus International Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2024

Primary Completion (Estimated)

January 16, 2027

Study Completion (Estimated)

January 27, 2027

Study Registration Dates

First Submitted

February 8, 2024

First Submitted That Met QC Criteria

February 12, 2024

First Posted (Actual)

February 20, 2024

Study Record Updates

Last Update Posted (Actual)

April 9, 2024

Last Update Submitted That Met QC Criteria

April 8, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRB-701-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Solid Tumor, Adult

Clinical Trials on CRB-701

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in South Korea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe