Clinical trial NCT06265727: A Phase 1/2 Study to Investigate CRB-701 in Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor, Adult
Keywords: nectin-4
Lead sponsor: Corbus Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
First posted: 2024-02-20
Enrollment: 348
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: A three part study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part A: To confirm the safety and tolerability and determine MTD and PADR for CRB-701
timeFrame: 21 days
measure: Part B & C: To evaluate efficacy in terms of Objective Response Rate (ORR)
timeFrame: Up to 6 months
Secondary outcomes:
measure: Parts A, B, & C: To characterize the safety profile of CRB-701
timeFrame: Up to 6 months
measure: Maximum observed plasma concentration of CRB-701 [total ADC] (Cmax)
timeFrame: Approximately 9 weeks
measure: Maximum observed plasma concentration of free MMAE (Cmax)
timeFrame: Approximately 9 weeks
measure: Part B & C : To evaluate efficacy in terms of Disease Control Rate (DCR)
timeFrame: Up to 6 months
measure: Maximum observed plasma concentration of Total CRB-701 antibody [Tab] (Cmax)
timeFrame: Approximately 9 weeks
measure: Time to reach Cmax of Total CRB-701 [Total ADC] (Tmax)
timeFrame: Approximately 9 weeks
measure: Time to reach Cmax of free MMAE (Tmax)
timeFrame: Approximately 9 weeks
measure: Time to reach Cmax of Total CRB-701 antibody [Tab] (Tmax)
timeFrame: Approximately 9 weeks
measure: Time to reach Cmax of Total CRB-701 antibody [Tab] (Cmax)
timeFrame: Approximately 9 weeks
measure: Total Area Under the plasma concentration-time curve of Total CRB-701 [total ADC] (AUC)
timeFrame: Approximately 9 weeks
measure: Total Area Under the plasma concentration-time curve of free MMAE (AUC)
timeFrame: Approximately 9 weeks
measure: Total Area Under the plasma concentration-time curve of Total CRB-701 antibody [Tab] (AUC)
timeFrame: Approximately 9 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: O'Neal Comprehensive Cancer Center at University of Alabama-Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: San Diego
country: United States
facility: Moores Cancer Centre at UC San Diego Health
state: California
city: San Francisco
country: United States
facility: Helen Diller Family Comprehensive Cancer Center - UCSF
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centres
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Orlando
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Hinsdale
country: United States
facility: Hope and Healing Cancer Center
state: Illinois
city: Boston
country: United States
facility: Dana-Faber Cancer Institute
state: Massachusetts
city: Lincoln
country: United States
facility: Nebraska Hematology Oncology
state: Nebraska
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Tyler
country: United States
facility: Texas Oncology
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center at University of Washington
state: Washington
city: Montpellier
country: France
facility: ICM-Val d'Aurelle
city: Poitiers
country: France
facility: CHU de Poitiers
city: St. Herblain
country: France
facility: Institut de Cancerologie de l'Ouest
city: Villejuif
country: France
facility: Gustave Roussy
city: Florence
country: Italy
facility: Careggi University Hospital
city: Milan
country: Italy
facility: European Institute of Oncology IRCCS
city: Rome
country: Italy
facility: Fondazione Policlinico Gemelli, IRCCS
city: Verona
country: Italy
facility: Centro Richerche Cliniche di Verona
city: Bucharest
country: Romania
facility: Aresnsia Research Clinic Bucharest
city: Cluj-Napoca
country: Romania
facility: Aresnsia Research Clinic Cluj-Napoca
city: Iaşi
country: Romania
facility: Centrul de Oncologie Sf. Nectarie
city: Iaşi
country: Romania
facility: Centrul de Oncologie Euroclinic
city: Barcelona
country: Spain
facility: Barcelona IOB Hospital Quironsalud (NEXT)
city: Barcelona
country: Spain
facility: Vall d-Hebron Institut d'Oncologia
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz (START)
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Adana
country: Turkey
facility: Adana Numune Egitim ve Arastirma Hastanesi (Adana City Education and Research Hospital)
city: Ankara
country: Turkey
facility: Ankara University
city: Ankara
country: Turkey
facility: Ankara Etlik City Hospital
city: Istanbul
country: Turkey
facility: Istanbul Medeniyet University
city: Birmingham
country: United Kingdom
facility: University of Birmingham NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: University of Cambridge NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Leeds
country: United Kingdom
facility: Leeds University Hospitals NHS Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' Clinical Research Facility
city: London
country: United Kingdom
facility: Imperial Experimental Cancer Medicine Centre
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Southampton
country: United Kingdom
facility: University of Southampton
city: Wirral
country: United Kingdom
facility: University of Liverpool - Clatterbridge Medical Centre
Study officials:
affiliation: Imperial College London
name: David Pinato, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Corbus International Ltd
name: Ian Hodgson, PhD
role: STUDY_DIRECTOR
affiliation: University of Chicago
name: Ari Rosenberg, MD
role: PRINCIPAL_INVESTIGATOR
References: