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

Phase 1

Recruiting

• Conditions: Solid Tumor, Adult
• Interventions: Drug: CRB-701

• 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 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 Timeline

• Study First Submitted: 2024-02-08
• Study First Submitted QC: 2024-02-12
• Study First Posted: 2024-02-20
• Study Start: 2024-04-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-23
• Last Update Posted: 2024-12-27
• Primary Completion: 2027-01-16
• Study Completion: 2027-01-27

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 420

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.

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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.

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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, once every three weeks
Part C Dose Expansion - Cohort 1	CRB-701	Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins
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 of CRB-701 and schedule, intravenous infusion over 30 mins
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 of CRB-701 and schedule, intravenous infusion over 30 mins

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 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
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
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 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 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 [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 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

Nebraska Hematology Oncology; 🇺🇸 Lincoln, Nebraska, United States

Carolina BioOncology Institute; 🇺🇸 Huntersville, North Carolina, United States

Texas Oncology; 🇺🇸 Tyler, Texas, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

Fred Hutchinson Cancer Center at University of Washington; 🇺🇸 Seattle, Washington, United States

ICM-Val d'Aurelle; 🇫🇷 Montpellier, France

CHU de Poitiers; 🇫🇷 Poitiers, France

Institut de Cancerologie de l'Ouest; 🇫🇷 St. Herblain, France

Gustave Roussy; 🇫🇷 Villejuif, France

Careggi University Hospital; 🇮🇹 Florence, Italy

European Institute of Oncology IRCCS; 🇮🇹 Milan, Italy

Fondazione Policlinico Gemelli, IRCCS; 🇮🇹 Rome, Italy

Centro Richerche Cliniche di Verona; 🇮🇹 Verona, Italy

Aresnsia Research Clinic Bucharest; 🇷🇴 Bucharest, Romania

Aresnsia Research Clinic Cluj-Napoca; 🇷🇴 Cluj-Napoca, Romania

Centrul de Oncologie Sf. Nectarie; 🇷🇴 Lasi, Romania

Centrul de Oncologie Euroclinic; 🇷🇴 Lasi, Romania

Barcelona IOB Hospital Quironsalud (NEXT); 🇪🇸 Barcelona, Spain

Vall d-Hebron Institut d'Oncologia; 🇪🇸 Barcelona, Spain

Fundacion Jimenez Diaz (START); 🇪🇸 Madrid, Spain

Hospital Clinico Universitario de Valencia; 🇪🇸 Valencia, Spain

Adana Numune Egitim ve Arastirma Hastanesi (Adana City Education and Research Hospital); 🇹🇷 Adana, Turkey

Ankara University; 🇹🇷 Ankara, Turkey

Ankara Etlik City Hospital; 🇹🇷 Ankara, Turkey

Istanbul Medeniyet University; 🇹🇷 Istanbul, Turkey

University of Birmingham NHS Foundation Trust; 🇬🇧 Birmingham, United Kingdom

University of Cambridge NHS Foundation Trust; 🇬🇧 Cambridge, United Kingdom

Velindre Cancer Centre; 🇬🇧 Cardiff, United Kingdom

Leeds University Hospitals NHS Trust; 🇬🇧 Leeds, United Kingdom

Guy's and St Thomas' Clinical Research Facility; 🇬🇧 London, United Kingdom

Imperial Experimental Cancer Medicine Centre; 🇬🇧 London, United Kingdom

The Christie Hospital; 🇬🇧 Manchester, United Kingdom

University of Southampton; 🇬🇧 Southampton, United Kingdom

University of Liverpool - Clatterbridge Medical Centre; 🇬🇧 Wirral, United Kingdom