Advanced Solid Tumor
Conditions
Brief summary
The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), Immunogenicity and preliminary antitumor activity of HC006 in subjects with advanced solid tumor malignancies. This study is a first-in-human (FIH) study of HC006 in subjects with advanced solid tumors.
Detailed description
HC006, a novel therapeutic monoclonal antibody that specifically binds to human C-C motif chemokine receptor 8 (CCR8) and is designed to selectively deplete tumor-infiltrating T regulatory cells (Tregs) with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). In mouse tumor models, HC006 has demonstrated excellent antitumor activity and safety profile. This first-in-human (FIH) study will be conducted in two parts. In the Dose-Escalation part, testing will be done on up to 31 subjects to determine the maximum tolerated dose (MTD) and the recommended dose (RD). In the Dose-expansion part, we will evaluate the safety and efficacy of the recommended dose of HC006 in the treatment of advanced solid tumor subjects without standard therapy.
Interventions
DRUGHC006
Specified dose on specified days
Sponsors
HC Biopharma Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have histologically confirmed and documented diagnosis of locally advanced unresectable or metastatic advanced solid tumor that is refractory to standard treatment, or intolerant to standard treatment, or for which no standard treatment exists. * At least one measurable disease for expansion cohorts per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1(dose escalation only requires at least one assessable lesion) * Agree to provide archived or fresh tumor tissue samples of primary or metastatic lesions for expansion cohorts. * Life expectancy ≥12 weeks * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Have adequate organ function as described in the protocol. * Agree to adopt effective contraceptive measures.
Exclusion criteria
* Prior exposure to CCR8 inhibitor or hypersensitivity to any ingredient of the study drug. * Treatment with any systemic anti-cancer treatment within 4 weeks before first dose of study drug. * Use of any live attenuated vaccines within 28 days. * With primary central nervous system (CNS) tumors or unstable CNS metastases. * Have active or history of autoimmune disease or immunodeficiency disease. * With active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy. * With any mental or cognitive impairment that may limit their understanding, implementation. * Major surgery within 4 weeks of study drug administration. * Have uncontrolled or severe illness, including but not limited to severe cardiovascular disease, interstitial lung disease or non-infectious pneumonia, or uncontrollable clinical third luminal effusion. * Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0. * History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma. * Women who are pregnant or breastfeeding. * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Dose Limiting Toxicities(DLTs)as assessed by protocol | up to 24 months | Incidence of Dose Limiting Toxicities(DLTs) |
| Number of participants with adverse events(AEs) as assessed by CTCAE v5.0 | up to 24 months | Incidence of adverse events(AEs) |
| Number of participants with Serious adverse events(SAEs)as assessed by CTCAE v5.0 | up to 24 months | Incidence of Serious adverse events(SAEs) |
| Percentage of Participants Experiencing Laboratory and ECG Abnormalities According to the NCI CTCAE v5.0 | up to 24 months | Percentage of Participants Experiencing Laboratory and ECG Abnormalities According to the NCI CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter:Area Under the Concentration-time Curve (AUC) | up to 24 months | Area Under the Concentration-time Curve (AUC) |
| Immunogenicity | up to 24 months | Incidence of anti-drug antibodies (ADAs) to HC006 |
| Overall Survival (OS) | up to 24 months | Time from first dose of the investigational drug to death from any cause. |
| Objective Response Rate (ORR) per RECIST 1.1 | up to 24 months | The sum of the proportions of subjects who achieved CR or PR in imaging evaluation as assessed by the investigator based on RECIST1.1 criteria. |
| Duration of response (DOR) per RECIST 1.1 | up to 24 months | Time from the first evaluated CR or PR until PD or death from any cause. |
| Time to progression (TTP) per RECIST 1.1 | up to 24 months | Time from first dose of the investigational drug to the tumor evaluation of PD. |
| Time To Response (TTR) per RECIST 1.1 | up to 24 months | Time from first dose of the investigational drug to the first tumor evaluation of CR or PR. |
| Disease Control Rate (DCR) per RECIST 1.1 | up to 24 months | The sum of proportions of subjects who achieved CR, PR, and SD in imaging evaluation. |
| Pharmacokinetic (PK) Parameter:Maximum serum concentration (Cmax) | up to 24 months | Maximum serum concentration (Cmax) |
| progression-Free Survival (PFS) per RECIST 1.1 | up to 24 months | Time from first dose of the investigational drug to PD or death from any cause. |
| PK Parameter:Time to reach Cmax (Tmax) | up to 24 months | Time to reach Cmax (Tmax) |
Countries
China
Contacts
Primary Contactlangxi Zhang, PhD
Outcome results
None listed