A Study of CBP-1018 in Patients With Advanced Solid Tumors

NCT04928612 | Recruiting Phase 1

• 1 other identifier: CBP-1018-101
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open-label, non-randomized, multi-center, phase I study of bi-ligand-drug conjugate CBP-1018 in patients with advanced solid tumors. This study will be conducted in 2 parts: Part A (Dose Escalation) and Part B (Dose Expansion). Both parts include screening period, treatment period, end of treatment (EOT)/withdrawal, safety follow-up (SFU) and long-term-follow-up (LTFU). CBP-1018 will be administrated on eligible subjects until disease progression, unacceptable toxicity, withdrawal of consent or Sponsor's decision to stop the study, etc.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (4)

• Incidence and severity of Adverse Events (AEs) in Part A

  Incidence of dose limiting toxicity (DLTs), treatment-emergent adverse events (TEAE), treatment-related adverse events, serious adverse events (SAEs) and clinically significant changes in vital signs, physical examinations, electrocardiogram (ECGs), and clinical laboratory tests per the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE 5.0).

  12 months

• MTD of CBP-1018 in Part A

  maximum tolerated dose（MTD）

  12 months

• Recommended Phase 2 dose (RP2D) of CBP-1018 in Part A

  The recommended Phase 2 dose (RP2D) is defined as the dose level chosen by the sponsor (in consultation with the investigators) based on safety,tolerability, efficacy, PK data collected during the dose escalation study of CBP-1018.

  12 months

• ORR in Part B

  ORR（Objective response rate） per RECIST 1.1 ,PCWG3 (only for bone lesions of prostate cancer)

  enrollment to end of treatment up to 3 years

Secondary Outcomes (10)

• Maximum serum concentration (Cmax)

  12 months

• Time to maximum serum concentration (Tmax) of CBP-1018

  12 months

• Elimination half-life (T1/2) of CBP-1018

  12 months

• AUC0-t of CBP-1018

  12 months

• Clearance (CL) in the serum of CBP-1018 per unit of time

  12 months

Other Outcomes (4)

• Neuroendocrine or small cell transformation-associated markers of mCRPC

  12 months

• Potential metabolites of CBP-1018

  12 months

• Biomarkers

  12 months

Study Arms (1)

Part A -CBP-1018 Dose escalation/Part B- CBP-1018 monotherapy

EXPERIMENTAL

Part A: CBP-1018 administrated iv Q 2 W (4 weeks/cycle), utilizing accelerated titration at lower doses (0.03 mg/kg and 0.06 mg/kg) and an i 3+3 design at following doses (0.08 mg/kg,0.10 mg/kg,0.12 mg/kg and 0.14 mg/kg, etc.), respectively. Part B：Further evaluate the efficacy and safety profile of CBP-1018 in 4 tumor-specific cohorts.Cohort 1 (Metastatic castration resistant prostate cancer, mCRPC)；(Advanced renal cell cancer, RCC); Cohort 3 (Advanced lung cancer, LC); Cohort 4 (Other advanced solid tumors).

Drug: CBP-1018

Interventions

CBP-1018 DRUG

CBP-1018 for injection, IV infusion

Part A -CBP-1018 Dose escalation/Part B- CBP-1018 monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent (ICF) prior to any study-specific procedures.
• Men or women ≥ 18 years old when signed ICF.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Life expectancy of ≥ 3 months, in the opinion of the Investigator.
• Pathologically documented, advanced solid tumor including metastatic castration resistant prostate cancer (mCRPC), advanced renal cell cancer (RCC), advanced lung squamous cell cancer (LSCC), etc.
• Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.
• At least one non-irradiated measurable lesion per RECIST 1.1 or bone lesion per PCWG3 (only for mCRPC), optional for low dose level (≤ 0.08 mg/kg) of Part A.
• Available archived or fresh tumor tissue samples, optional for low dose level (≤ 0.08 mg/kg) of Part A.
• Adequate bone marrow and organ function, defined as:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, not requiring growth factor support for at least 28 days prior to the first dose of CBP-1018.
• Hemoglobin (Hb) ≥ 100 g/L, not requiring transfusion support for at least 14 days or growth factor support for at least 28 days prior to the first dose of CBP-1018.
• Platelet count ≥ 100 × 109/L, not requiring transfusion support for at least 7 days prior to the first dose of CBP-1018.
• Total bilirubin (TBIL) ≤ 1.5 × ULN, alkaline phosphatase (ALP) ≤ 1.5 × ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0× ULN if no demonstrable liver metastases.
• TBIL≤ 1.5 × ULN, ALT and AST ≤ 5.0 × ULN in the presence of liver metastases.
• TBIL \< 2.0 × ULN for subjects with documented Gilbert's syndrome or \< 3.0 × ULN for subjects for whom the indirect bilirubin level suggests an extrahepatic source of elevation.

You may not qualify if:

• Known prior or suspected hypersensitivity to study drugs or any component in their formulations.
• Concurrent malignancy within 5 years prior to the first dose of CBP-1018, other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer not requiring treatment, ductal carcinoma in situ of the breast, or \< T1 urothelial carcinoma.
• Active central nervous system (CNS) metastases. Previously diagnosed CNS metastases are eligible if have been treated and recovered from the acute effects of radiation therapy or surgery prior to the first dose of CBP-1018, have discontinued corticosteroid treatment for CNS metastases for at least 4 weeks and are neurologically stable.
• Major surgery, systemic anticancer therapy (chemotherapy, targeted therapy, immunotherapy, endocrine therapy, biotherapy) or participation in other therapeutic studies within 4 weeks prior to the first dose of CBP-1018.
• Radiotherapy administrated within 21 days prior to the first dose of CBP-1018, or localized palliative radiotherapy administered within 7 days prior to the first dose of CBP-1018.
• Any toxicities attributed to prior anti-cancer therapy, other than alopecia and fatigue, that have not resolved to Grade 1 (NCI CTCAE 5.0) or baseline prior to the first dose of CBP-1018.
• Poorly controlled concurrent diseases as diabetes, hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \> 100 mmHg), etc.
• History of any of the following cardiovascular conditions within 12 months of enrollment: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, class III or IV congestive heart failure, as defined by the New York Heart Association.
• History of clinically significant lung diseases as interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis, or suspected to have these diseases by imaging at screening period.
• Active bleeding disorder or other history of grade ≥ 3 hemorrhage within 4 weeks prior to the first dose of CBP-1018.
• Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access device or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed.
• History of deep vein thrombosis or pulmonary embolism within 6 months prior to the first dose of CBP-1018.
• Active infection requiring intravenous (IV) antibiotics within 1 weeks prior to the first dose of CBP-1018.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Positive Hepatitis B Surface Antigen (HepBsAg) (indicative of chronic Hepatitis B), positive Hepatitis total core antibody with negative HepBsAg (suggestive of occult hepatitis B) or detectable Hepatitis C virus Ribonucleic acid (RNA) by PCR (Hepatitis C Antibody test for screening, followed by PCR for Hepatitis C virus RNA if HepCAb is positive).

Sponsors & Collaborators

• Coherent Biopharma (Suzhou) Co., Ltd.: lead

Study Sites (2)

Sun Yat-Sen memorial hospital, Sun Yat-Sen University

Guangzhou, Guangdong, 510288, China

NOT YET RECRUITING

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

Study Officials

• Hai Huang, Ph D

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiangang Yu, Ph D

CONTACT

0512-85550899; jiangang.yu@coherentbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2021
• First Posted: June 16, 2021
• Study Start: November 4, 2021
• Primary Completion: October 1, 2024
• Study Completion: December 1, 2024
• Last Updated: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)