A Phase I/II, Open-label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of HB0045 in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- HB0045 Drug Product
- Conditions
- Solid Tumor, Adult
- Sponsor
- Shanghai Huaota Biopharmaceutical Co., Ltd.
- Enrollment
- 71
- Locations
- 3
- Primary Endpoint
- Phase II: Objective response rate (ORR)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, aged ≥ 18 years.
- •The subject can understand and willing to sign the ICF and is willing and able to comply with all study procedures.
- •Phase I: Patients with histologically or cytologically confirmed locally advanced, recurrent, or metastatic solid tumors (or clinically diagnosed hepatocellular carcinoma) that failed (progressed on or are intolerant of) all standard therapies known to provide clinical benefit; \[These solid tumors include but not limited to: pancreatic, colorectal, ovarian, breast, lung, head and neck, prostate, renal cancer, and sarcoma, etc.\]
- •Phase II: Patients who have had at least one systemic therapy and has progressed, and might benefit from the study drug in the Investigator's judgment, and have the following histological types (The types of tumors and the number of treatment lines may be adjusted based on phase I results and /or SRC discussions):
- •a) Pancreatic cancer cohort: i. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma. ii. Unresectable, locally advanced recurrent or metastatic. b) CRC cohort: i. Histologically or cytologically confirmed colorectal cancer. ii. Molecular typing: non-dMMR/ non-MSI-H colorectal cancer. c) Ovarian cancer cohort: i. Histologically or cytologically confirmed unresectable metastatic ovarian, fallopian tube or peritoneal cancer ii. Epithelial type including high-grade serous cell carcinoma, endometrioid carcinoma or clear cell carcinoma.
- •iii. No history of ileus (including signs or symptoms of ileus) within 3 months prior to screening.
- •iv. Patients who had not received enterostomy within 3 months prior to screening.
- •v. Have failed (progressed on or are intolerant of) all standard therapies known to provide clinical benefit; including but not limited to treatment with platinum-based chemotherapy if platinum-sensitive disease, and treatment with chemotherapy + bevacizumab if platinum-resistant and have not received prior bevacizumab.
- •d) Other advanced cancer cohort(s): Tumor specific type that demonstrated partial response to HB0045 in dose escalation phase.
- •At least one measurable lesion as per RECIST v. 1.1 defined as non-nodal lesions having at least one dimension with a minimum size of 10 mm in the longest diameter by CT or MRI scan or ≥15 mm in short axis for nodal lesions. Radiographic disease assessment at baseline can be performed up to 21 days prior to the first dose.
Exclusion Criteria
- •Concurrent malignancy \< 5 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, localized prostate cancer, ductal carcinoma in situ of the breast, or \< T1 urothelial carcinoma. Patients with prostate cancer that is under active surveillance are eligible.
- •Have clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain or meningeal metastases may participate and be eligible for treatment provided they are stable and asymptomatic. Patients with asymptomatic brain or meningeal metastasis or patients who are symptomatically stable after treatment and are on≤ 10 mg/d prednisone or equivalent are eligible.
- •Cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, or New York Heart Association (NYHA) class III or IV heart failure occurred within 6 months before study admission; QT-interval corrected according to Fridericia's formula (QTcB) \> 480 milliseconds (ms) obtained from three consecutive ECGs; uncontrolled arrhythmia \< 3 months of study entry (judged by the Investigator). Patients with rate-controlled arrhythmias may be eligible for study entry at discretion of the Investigator.
- •Active autoimmune disease or history of autoimmune disease requiring systemic therapy \< 2 years prior to screening except hypothyroidism, vitiligo, Grave's disease, Hashimoto's disease, or Type I diabetes. Patients with childhood asthma or atopy that has not been active in the 2 years prior to study screening are eligible.
- •Patients who have previously received allogeneic stem cell or solid organ transplantation.
- •History of severe allergic reactions, grade 3-4 allergic reactions to treatment with another monoclonal antibody or known to be allergic to protein drugs or recombinant proteins or excipients in HB0045 drug formulation.
- •History of Grade 3-4 immune-related adverse events (irAEs) or irAEs requiring discontinuation of prior therapies, (except for Grade 3 endocrinopathy that is managed with hormone replacement therapy).
- •Use of systemic corticosteroids in a dose equivalent to ≥10 mg/day of prednisone or other immunosuppressive agents \< 2 weeks prior to screening; the use of topical, intraocular, intraarticular, intranasal, or inhaled corticosteroids and systemic steroids to prevent (e.g., allergy to contrast agents) or treat non-autoimmune condition (e.g., delayed hypersensitivity caused by exposure to allergens), or short course (\< 5 days) will be allowed.
- •Have received antibiotics lasting over 1 week within 28 days prior to first dose.
- •Have received or will receive a live vaccine within 4 weeks prior to the first dose.
Arms & Interventions
HB0045
HB0045 IV every 3 weeks (q3w)
Intervention: HB0045 Drug Product
Outcomes
Primary Outcomes
Phase II: Objective response rate (ORR)
Time Frame: Up to 24 Months
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
Phase I: The incidence of Dose-Limiting Toxicities (DLTs) in patients receiving HB0045
Time Frame: Up to 21 Days
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%.
Phase I: Maximum Tolerated Dose(MTD)
Time Frame: Up to 36 Moths
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.
Secondary Outcomes
- Anti-drug antibodies (ADA)(Up to 24 Moths)
- Phase I＆II：Maximum serum concentration(Cmax)(within 48 hours after single HB0045 administered)
- Phase I＆II：Half-life (t1/2)(within 3 months after first dose of HB0045 administered)
- Phase I＆II：time of maximum concentration(Tmax)(within 3 months after first dose of HB0045 administered)
- Phase I＆II：Maximum serum concentration(Cmax,ss)(within 3 months after first dose of HB0045 administered)
- Phase I＆II：Half-life (t1/2, ss)(within 3 months after first dose of HB0045 administered)
- Phase I＆II：time of maximum concentration(Tmax, ss)(within 3 months after first dose of HB0045 administered)
- Phase I＆II：Area under the curve (AUC0-t）(Up to 24 Months)
- Phase I＆II：Area under the curve (AUC0-∞）(Up to 24 Months)
- Disease control rate (DCR)(Up to 24 Months)
- Duration of response (DOR)(Up to approximately 2 years)
- Progression-free survival (PFS)(Up to approximately 2 years)
- Up to approximately 2 years(up to 2 years)