A Phase Ia/Ib, Open-Label, Multi-center, First in Human and Expansion Study to Assess the Safety, Tolerance, and Pharmacokinetics of the Novel Antitumor Agent CBP-1008 in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- CBP-1008
- Conditions
- Advanced Solid Tumor
- Sponsor
- Coherent Biopharma (Suzhou) Co., Ltd.
- Enrollment
- 143
- Locations
- 3
- Primary Endpoint
- To determine the maximum tolerated dose (MTD)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The primary objective of this phase I study is to evaluate the safety and potential efficacy and to determine the recommended phase 2 dose (RP2D) of CBP-1008, a bi-specific ligand conjugated drugs in patients with advanced solid tumors.
Detailed Description
This phase Ia/Ib, open-label, multicenter study has two stages. The Ia stage is a dose-escalation study that will focus on safety, tolerability, pharmacokinetics, MTD and RP2D. Patients with advanced solid tumor who failed from previous standard treatment or without standard therapy exists will be enrolled in the phase Ia study. DLT observation period is 28 days. Patients in phase Ib part will be recruited into certain tumor cohorts and receive RP2D CBP-1008 iv infusion every two weeks. Primary efficacy of ORR, DCR, PFS, etc., will be evaluated. The correlation between tumor response and the receptors will be explored. Safety information will be collected in phase Ib stage.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ranged 18-70 years (including the boundaries) when signed informed consent form (ICF)
- •Has a life expectancy of ≥ 3 months
- •Phase Ia: patients with advanced malignant solid tumor who:
- •have progressed on or are intolerant to standard therapy, or
- •no standard therapy exists
- •Phase Ib disease specific Cohorts:
- •Cohort 1: Platinum-resistant advanced high-grade serous ovarian cancer, fallopian tube cancer or primary peritoneal cancer.Platinum resistance was defined as progression or recurrence within 6 months after the last dose of platinum. Patients with primary platinum refractory disease are excluded
- •Cohort 2: Metastatic triple-negative breast cancer
- •Based on most recently analyzed biopsy or other pathological specimens, TNBC was confirmed histologically or cytologically
- •Patients have received at least 2 previous systemic chemotherapy regimens for local advanced/metastasis disease. If the patients in the early phase develop into unresectable locally advanced or metastatic disease within 12 months after adjuvant or neoadjuvant chemotherapy, the regimens will be regarded as one of the previous systemic chemotherapy regimens
Exclusion Criteria
- •History of allergic reactions to any component of the CBP-1008
- •Concurrent malignancy(ies) within 3 years prior to screening other than adequately treated cervical carcinoma-in-situ, skin cancer of basal cell or squamous cell carcinoma, local prostate cancer after radical operation, ductal carcinoma in situ after radical operation
- •History of epilepsy
- •Active or symptomatic central nervous system metastasis and / or cancerous meningitis with the exception of, asymptomatic or stable brain metastases
- •History of congestive heart failure of the New York Heart Association Functional Classification III/IV, unstable angina pectoris, persistent atrial fibrillation, ventricular arrhythmia or conduction block; with risk factors for, or are receiving medications known to prolong QT interval, refractory hypertension (except hypertension patients whose blood pressure is controlled below 140 / 90mmHg by drugs)
- •Significant surgical interventions within 21 days prior to the first dose of CBP-1008 or with ongoing post-operative complications
- •Radiotherapy administrated within 21 days prior to the first dose of CBP-1008
- •Interstitial lung disease, non-infectious pneumonia or a history of poorly controlled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, etc
- •Active infections requiring systemic treatment, active viral hepatitis or active tuberculosis
- •Pericardial effusion with important clinical significance
Arms & Interventions
Ia stage - CBP-1008 Dose escalation/ Ib stage - CBP-1008 monotherapy
Ia:Patients will receive CBP-1008 IV infusion every 2 weeks until disease progression, intolerability, informed consent withdraw, or other reasons leading to treatment discontinue. Ib:Patients will receive CBP-1008 RP2D IV infusion every two weeks until disease progression, intolerability, informed consent withdraw, or other reasons leading to treatment discontinue.
Intervention: CBP-1008
Outcomes
Primary Outcomes
To determine the maximum tolerated dose (MTD)
Time Frame: Up to 28 days after the first dose of CBP-1008
Dose limiting toxicity (DLT) will be assessed by NCI CTCAE v4.03. MTD is defined as the previous dose level at which 2 out of 3 participants or 2 out of 6 participants experienced DLT.
Incidence and severity of Adverse Events (AEs)
Time Frame: up to 12 months
Assessed by number of patients with AE, Treatment-Emergent Adverse Event (TEAE), serious adverse event (SAE), and discontinuation of study drug due to AE.
Secondary Outcomes
- Clearance (CL) in the serum of CBP-1008 per unit of time(up to 12 months)
- Recommended Phase II Dose (RP2D)(up to 12 months)
- Duration of Response (DOR)(up to 12 months)
- Maximum serum concentration (Cmax) of CBP-1008(up to 12 months)
- Time to maximum serum concentration (Tmax) of CBP-1008(up to 12 months)
- Elimination half-life (T1/2) of CBP-1008(up to 12 months)
- Objective Response Rate (ORR)(up to 12 months)
- Overall survival rate (OS)(up to 12 months)
- AUC0-t of CBP-1008(up to 12 months)
- 6. The percentage of participants with anti-drug antibody (ADA) positive after dosing CBP-1008(up to 12 months)
- Clinical benefit rate (CBR)(up to 12 months)
- Progression-free survival rate (PFS)(up to 12 months)