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

Solid Tumor, Adult Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06265727
• Other study ID #: CRB-701-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 1, 2024
• Est. completion date: January 27, 2027

Study information

• Verified date: May 2024
• Source: Corbus Pharmaceuticals Inc.
• Contact: Ian Hodgson, PhD
• Phone: +1 (617) 963-0105
• Email: Clinical[@]Corbuspharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: January 27, 2027
• Est. primary completion date: January 16, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor, Adult

Intervention

Drug:
• CRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)

Locations

Country	Name	City	State
Spain	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
Turkey	Adana Numune Egitim ve Arastirma Hastanesi (Adana City Education and Research Hospital)	Adana
Turkey	Ankara Etlik City Hospital	Ankara
Turkey	Ankara University	Ankara
Turkey	Istanbul Medeniyet University	Istanbul
United Kingdom	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 States	Dana-Faber Cancer Institute	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Rocky Mountain Cancer Centres	Denver	Colorado
United States	City of Hope Cancer Center	Duarte	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Hope and Healing Cancer Center	Hinsdale	Illinois
United States	Carolina BioOncology Institute	Huntersville	North Carolina
United States	Nebraska Hematology Oncology	Lincoln	Nebraska
United States	Yale Cancer Center	New Haven	Connecticut
United States	Florida Cancer Specialists	Orlando	Florida
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	Texas Oncology	Tyler	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Corbus Pharmaceuticals Inc.	CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.

Countries where clinical trial is conducted

United States,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: To confirm the safety and tolerability and determine MTD and PADR for CRB-701	Occurrence of Dose Limiting Toxicities as defined in the protocol	21 days
Primary	Part B & C : To evaluate efficacy in terms of Disease Control Rate (DCR)	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
Primary	Part B & C: To evaluate efficacy in terms of Objective Response Rate (ORR)	ORR is the percentage of participants that achieve a response (CR + PR) using RECIST 1.1	Up to 6 months
Secondary	Parts A, B, % C: To characterize the safety profile of CRB-701	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
Secondary	Maximum observed plasma concentration of CRB-701 [total ADC] (Cmax)	Maximum observed plasma concentration of total ADC after single and multiple doses	Approximately 9 weeks
Secondary	Maximum observed plasma concentration of free MMAE (Cmax)	Maximum observed plasma concentration of free MMAE after single and multiple doses	Approximately 9 weeks
Secondary	Maximum observed plasma concentration of Total CRB-701 antibody [Tab] (Cmax)	Maximum observed plasma concentration of free MMAE after single and multiple doses	Approximately 9 weeks
Secondary	Time to reach Cmax of Total CRB-701 [Total ADC] (Tmax)	The amount of time to reach Cmax after single and multiple dose administration of CRB-701 (Total ADC)	Approximately 9 weeks
Secondary	Time to reach Cmax of free MMAE (Tmax)	The amount of time to reach Cmax after single and multiple dose administration of free MMAE	Approximately 9 weeks
Secondary	Time to reach Cmax of Total CRB-701 antibody [Tab] (Tmax)	The amount of time to reach Cmax after single and multiple dose administration of Tab	Approximately 9 weeks
Secondary	Time to reach Cmax of Total CRB-701 antibody [Tab] (Cmax)	Maximum observed plasma concentration of free MMAE after single and multiple doses	Approximately 9 weeks
Secondary	Total Area Under the plasma concentration-time curve of Total CRB-701 [total ADC] (AUC)	Maximum observed plasma concentration of free MMAE after single and multiple doses	Approximately 9 weeks
Secondary	Total Area Under the plasma concentration-time curve of free MMAE (AUC)	Area under the plasma concentration versus time curve after single and multiple dose administration of free MMAE	Approximately 9 weeks
Secondary	Total Area Under the plasma concentration-time curve of Total CRB-701 antibody [Tab] (AUC)	Area under the plasma concentration versus time curve after single and multiple dose administration of Tab	Approximately 9 weeks