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

Corbus Pharmaceuticals

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Solid Tumor, Adult

Treatments: Drug: CRB-701

Study type: Interventional

Funder types: Industry

Identifiers

NCT06265727

CRB-701-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 420 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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420 participants in 11 patient groups

Part A Dose Escalation - CRB-701 Dose Level 1

Experimental group

Description:

CRB-701 Dose level 1, intravenous infusion over 30 mins, Dose schedule 1

Treatment:

Drug: CRB-701

Part A Dose Escalation - CRB-701 Dose Level 2

Experimental group

Description:

CRB-701 Dose Level 2, intravenous infusion over 30 mins, Dose schedule 1

Treatment:

Drug: CRB-701

Part A Dose Escalation - CRB-701 Dose Level 3

Experimental group

Description:

CRB-701 Dose Level 3, intravenous infusion over 30 mins, dose schedule 1

Treatment:

Drug: CRB-701

Part A Dose Escalation - CRB-701 Dose Level 4

Experimental group

Description:

CRB-701 Dose Level 4, intravenous infusion over 30 mins, dose schedule 1

Treatment:

Drug: CRB-701

Part B Dose Optimization: CRB-701 High dose

Experimental group

Description:

Selected high dose of CRB-701, intravenous infusion over 30 mins, dose schedule 1

Treatment:

Drug: CRB-701

Part B Dose Optimization: CRB-701 low dose

Experimental group

Description:

Selected Low dose of CRB-701, intravenous infusion over 30 mins, once every three weeks

Treatment:

Drug: CRB-701

Part C Dose Expansion - Cohort 1

Experimental group

Description:

Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins

Treatment:

Drug: CRB-701

Part C Dose Expansion - Cohort 2

Experimental group

Description:

Recommended Phase 2 dose and schedule of CRB-701, intravenous infusion over 30 mins

Treatment:

Drug: CRB-701

Part C Dose Expansion - Cohort 3

Experimental group

Description:

Recommended Phase 2 dose of CRB-701 and schedule, intravenous infusion over 30 mins

Treatment:

Drug: CRB-701

Part C Dose Expansion - Cohort 4

Experimental group

Description:

Recommended Phase 2 dose of CRB-701 and schedule, intravenous infusion over 30 mins

Treatment:

Drug: CRB-701

Part C Dose Expansion - Cohort 5

Experimental group

Description:

Recommended Phase 2 dose of CRB-701 and schedule, intravenous infusion over 30 mins

Treatment:

Drug: CRB-701