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; Drug: Anti-PD-1

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? 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. They will have blood tests, CT or MRI Scans, and other assessments to measure whether CRB-701 has an 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 Maximum Tolerated Dose (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 evaluate two dose levels of CRB-701 alone and in combination with anti-PD-1 by using a time-to-event Bayesian optimal Phase 2 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 recommended dose level of CRB-701 for further exploration defined in Part B will explore CRB-701 alone or combined with anti-PD-1 in up to seven separate cohorts of participants with advanced tumors known to express Nectin-4.

Enrollment: 348 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 having exhausted all appropriate lines of therapy or have no other standard therapy with proven clinical benefit. In Part C, HNSCC participants may enroll as first-line therapy.

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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348 participants in 15 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

Treatment:

Drug: CRB-701

Part C Dose Expansion - Cohort 1

Experimental group

Description:

Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins followed by infusion with anti-PD-1

Treatment:

Drug: Anti-PD-1

Drug: CRB-701

Part C Dose Expansion - Cohort 2

Experimental group

Description:

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

Treatment:

Drug: CRB-701

Part C Dose Expansion - Cohort 3

Experimental group

Description:

Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins followed by infusion with anti-PD-1

Treatment:

Drug: Anti-PD-1

Drug: CRB-701

Part C Dose Expansion - Cohort 4

Experimental group

Description:

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

Treatment:

Drug: CRB-701

Part C Dose Expansion - Cohort 5

Experimental group

Description:

Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins followed by infusion with anti-PD-1

Treatment:

Drug: Anti-PD-1

Drug: CRB-701

Part B Dose Optimization: CRB-701 high dose combined with anti-PD-1

Experimental group

Description:

Selected high dose of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1

Treatment:

Drug: Anti-PD-1

Drug: CRB-701

Part B Dose Optimization: CRB-701 low dose combined with anti-PD-1

Experimental group

Description:

Selected low dose of CRB-701, intravenous infusion over 30 mins followed by infusion with anti-PD-1

Treatment:

Drug: Anti-PD-1

Drug: CRB-701

Part C Dose Expansion - Cohort 6

Experimental group

Description:

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

Treatment:

Drug: CRB-701

Part C Dose Expansion - Cohort 7

Experimental group

Description:

Recommended CRB-701 dose and schedule, intravenous infusion over 30 mins followed by infusion with anti-PD-1

Treatment:

Drug: Anti-PD-1

Drug: CRB-701