Solid Tumor, Adult
Conditions
Keywords
nectin-4
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? 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.
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 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.
Interventions
DRUGCRB-701
Nectin-4 targeted Antibody Drug Conjugate (ADC)
DRUGAnti-PD-1
checkpoint inhibitor
Sponsors
CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
Corbus Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A three part study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 [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 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 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 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 |
Countries
France, Italy, Moldova, Romania, Spain, United Kingdom, United States
Contacts
Primary ContactIan Hodgson, PhD
Backup ContactRodney Carter, BSc
Outcome results
None listed