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Patients will be assigned to dose regimens in the order of enrollment and receive their assigned fixed dose of HB0045 via intravenous infusion, Q3W.

HB0045 Drug Product

Nashat Gabrail

Park Haeseong

Siqing Fu

Yongmin Yang

This is a phase I/II, open-label, multicenter study . During the study, subjects will be evaluated for safety, toxicity, tolerability, PK/PD, immunogenicity, biomarkers, and antitumor activity of HB0045. The phase I study will enroll up to 54 subjects with advanced solid tumors who have progressed on or after standard of care therapy and for whom there is no further treatment available that in the judgement of the patient's physician would be beneficial. One cycle is defined as 21 days.

During the phase I study, the safety and tolerability of HB0045 will be evaluated in patients with advanced solid tumors including understanding of the preliminary efficacy. During this phase of the study, DLTs, MTD and MTD range will be observed which will inform RP2D. Phase I:Approximately 54 patients will receive HB0045 as a monotherapy at escalating doses.One cycle is defined as 3 weeks (21 days).

In the phase II study, the safety and preliminary efficacy of HB0045 at the RP2D will be evaluated in cohorts of patients with pancreatic, colorectal, ovarian cancer and/or other solid tumors.Phase II:During the dose escalation process, expansion cohorts will be conducted based on the preliminary RP2D.A Simon 2-stage design will be utilized with a stopping rule to allow for early termination of a particular cohort at the end of Stage 1 if patients have insufficient responses to HB0045. During Stage 1, 9 evaluable patients will be enrolled in each cohort; if no responses are observed within the cohort, then the cohort will be discontinued. If at least 1 response is observed, 8 additional evaluable patients will be enrolled in the cohort (Stage 2), for a maximum of 17 evaluable patients per cohort.

Phase I: Dose escalation with a conventional 3+3 design, including 1.5、5、15、30 and 40mg/kg dose group Phase II：Dose expansion phase. During the dose escalation process, expansion cohorts will be conducted based on the preliminary RP2D. A Simon 2-stage design will be utilized with a stopping rule to allow for early termination of a particular cohort at the end of Stage 1 if patients have insufficient responses to HB0045.

A Study of HB0045 Injection in Patients With Advanced Solid Tumors

A Phase I/II, Open-label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of HB0045 in Patients With Advanced Solid Tumors

DLTs will be assessed during the dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle (3 weeks) of treatment.A Bayesian Logistic Regression Model (BLRM) based approach will be used to identify the set of HB0045 doses where the incidence of DLTs is no larger than 33%.

Maximum Tolerated Dose is defined as the highest dose in which the number of cases of DLT is less than 1/3 of the total patients in the first treatment cycle (DLT evaluation period) of the dose escalation phase.

During the dose escalation phase of the study, if ≥33% DLTs occurred at a certain dose level, the maximum tolerated dose would be the dose level below that level, and if no ≥33% DLTs occurred after escalation to the highest dose, the highest dose will be considered MTD.

ORR defined as the number of patients were confirmed complete response(CR) and/or partial response(PR) according to RECIST 1.1 divided by the patients with at least one tumour evaluation

Incidence of positive anti-drug antibodies(ADA).

* Cmax refers to The maximum blood concentration of HB0045 after administration.
* Sample concentration analysis method adopts ELISA .
* parameters will be calculated by Phoenix WinNonlin version 8.3 using non-compartmental analysis.

* t1/2 refers to the time of a half reduction of total drug concentration in the body.
* parameters will be calculated by Phoenix WinNonlin version 8.3 using non-compartmental analysis.

* Cmax, ss refers to The maximum blood concentration of HB0045 after four cycles administration.
* Sample concentration analysis method adopts ELISA .
* parameters will be calculated by Phoenix WinNonlin version 8.3 using non-compartmental analysis.

* t1/2, ss refers to the time of a half reduction of total drug concentration in the body after four cycles of administration of HB0045.
* parameters will be calculated by Phoenix WinNonlin version 8.3 using non-compartmental analysis.

Peak time after HB0045 administration. The parameters will be calculated by Phoenix WinNonlin version 8.3 using non-compartmental analysis

AUC0-t refers to Area under the curve (AUC) from zero up to definite time t with extrapolation of the terminal phase.

Parameters will be calculated by Phoenix WinNonlin version 8.3 using noncompartmental analysis.

Area under the concentration-time curve from zero up to ∞ with extrapolation of the terminal phase.

Parameters will be calculated by Phoenix WinNonlin version 8.3 using noncompartmental analysis.

DCR defined as the number of patients were confirmed CR and/or PR and/or stable disease(SD) according to RECIST 1.1 divided by the patients with at least one tumour evaluation

DOR defined as time from the first record of CR or PR to the first record of disease. DOR as evaluated by investigators according to RECIST v1.1.

PFS is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first)

Overall survival is defined as the time from the start of treatment with HB0045 until death due to any cause. OS as evaluated by investigators according to RECIST v1.1.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of HB0045 Injection in Patients With Advanced Solid Tumors	NCT06056323	Solid Tumor, Ad...	HB0045 Drug Pro...	18 Years -	Shanghai Huaota Biopharmaceutical Co., Ltd.
A Study of HB0045 Injection in Patients With Advanced Solid Tumors	NCT06056323	Solid Tumor, Ad...	HB0045 Drug Pro...	18 Years -	Shanghai Huaota Biopharmaceutical Co., Ltd.

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