Solid Cancer
Conditions
Brief summary
This is a non-randomized, open-label, dose-escalation, and dose-expansion Phase Ib/IIa study to evaluate the safety, tolerability, PK, PD, and preliminary antitumor activity of HCB101 administered in combination with standard or approved anticancer therapies in subjects with advanced solid tumors. The trial includes a Part-I (Phase Ib) of the dose-escalation phase and a Part-II (Phase IIa) of the dose-expansion phase. Part-I: Dose-escalation phase (Phase Ib): Part I uses a standard 3+3 dose-escalation design to characterize safety and tolerability and to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of HCB101 when administered in combination regimens. The study includes 14 planned cohorts (Cohorts 1-9, including sub-cohorts 3a-3d and 6a-6c). Part-II: Dose-expansion phase (Phase IIa) Based on safety, tolerability, PK/PD, and emerging antitumor activity observed in Part-I (Phase Ib), selected dose levels, tumor types, and combination regimens will be further investigated in Part-II (Phase IIa).
Interventions
DRUGHCB101
QW
DRUGTrastuzumab
8 mg/kg IV loading dose on Day 1 of cycle 1, then 6 mg/kg IV every 21 days;
DRUGPertuzumab
840 mg IV on Day 1, cycled every 21 days;
DRUGOxaliplatin
130 mg/m2 IV on Day 1, cycled every 21 days
DRUGCapecitabine
1000 mg/m2 PO BID on Days 1-14, Cycled every 21 days
DRUGRamucirumab
8 mg/kg IV on Days 1 and 15, Cycled every 28 days
DRUGPaclitaxel
80 mg/m2 IV on Days 1, 8, and 15, Cycled every 28 days
DRUGBevacizumab
5 mg/kg IV on Day 1, Repeat every 2 weeks;
DRUGCetuximab
400 mg/m2 first infusion, followed by 250 mg/m2 IV weekly;
DRUGIrinotecan
180 mg/m2 IV over 30-90 minutes on Day 1 every 2 weeks
DRUGLeucovorin
400 mg/m2 IV on Day 1 every 2 weeks
DRUG5-FU
400 mg/ m2 IV bolus on Day 1, followed by 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion Repeat every 2 weeks
DRUGToripalimab
240 mg/kg IV on Day 1 Cycled every 21 days
DRUGAlbumin-bound paclitaxel
125 mg/m2 IV on day 1 and Day 8 Cycled every 21 days
DRUGPembrolizumab
200 mg IV day 1; given every 21 days
AUC=5, IV on D1, Q3W for 4\~6 cycles
DRUGEtoposide
100mg/m2, IV on D1, 2, 3, Q3W for 4\~6 cycles
DRUGAtezolizumab
1200 mg IV on D1, Q3W
DRUGTrastuzumab deruxtecan
5.4 mg/kg IV on D1, Q3W
Sponsors
FBD Biologics Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects are able to understand and willing to provide signed informed consent. 2. Male and female subjects of ≥18 years of age, inclusive, at the time of signing the informed consent. 3. With histologically/cytologically confirmed diagnosis of advanced solid tumors as described below: 1\) Cohort 1- Gastric Cancer, HER-Positive (First-Line): 2) Cohort 2 - Gastric Cancer (Second-Line): 3) Cohort 3 - Colorectal Cancer (Second-Line): 4) Cohort 4 - Triple-Negative Breast Cancer (First-Line): 5) Cohort 5 - Gastric Cancer, HER2 Medium/Low/Negative (First-Line): 6) Cohort 6 - Head and Neck Squamous Cell Carcinoma: 7) Cohort 7 - Ovarian Cancer: 8) Cohort 8 - Hepatocellular Carcinoma: 9) Cohort 9 - Extensive-Stage Small Cell Lung Cancer: 4. Have adequate organ function, as indicated by the following laboratory parameters below (had not received a blood transfusion, apheresis infusion, erythropoietin, granulocyte colony-stimulating factor, and other relevant medical support within 14 days before the administration of the first dose of study intervention).
Exclusion criteria
1. With a known history of hypersensitivity to any components of the study intervention. 2. Prior/Concomitant Therapy/Treatment: 1. Subjects who have undergone major surgery or radical radiotherapy within 28 days before the first dose of study intervention. 2. Subjects who have received systemic antitumor therapies within the following washout periods prior to the first dose of study intervention: * 28 days for curative radiotherapy, immunotherapy, or targeted therapy, etc. * 14 days for chemotherapy, palliative radiotherapy, endocrine therapy, or herbal medicine or traditional therapies with known or claimed antitumor activity. 3. Subjects who have used a radioactive drug (Strontium, Samarium, etc.) within 56 days before the first dose of the study intervention. 4. Subjects who are active using of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on a case-by-case basis. Daily low dose of aspirin use (≤ 100 mg QD in Mainland China; ≤ 81 mg QD in the United States) is allowed. 5. Subjects who have received any treatment targeting the CD47 or SIRPα pathway. 6. Subjects who have received or plan to receive live virus or bacterial vaccine within 28 days before the first dose of study intervention while the subject receives the study intervention. 3. Participation in another clinical study with an investigational product administered or investigational device used in the last 28 days (If half-life is not clear) or 5 half-lives (If half-life is clear, the longer time one prevails) before receiving the first dose of study intervention. 4. Subjects who have received any treatment targeting the CD47 or SIRPα pathway. 5. An uncontrolled acute infection. 6. Known to have a history of alcoholism or drug abuse. 7. Any other medical (e.g., Child-Pugh class B or C, pulmonary, metabolic, congenital, endocrinal or CNS disease, etc.), psychiatric, or social condition deemed by the Investigator to be likely to interfere with a subject's rights, safety, welfare or ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number/incidence and percentage of subjects with adverse events. | 12 months | To evaluate the safety and tolerability of HCB101 |
| Number of subjects with Maximal tolerance dose (MTD) of HCB101 | 12 months | To evaluate the tolerability of HCB101 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Rate Response (ORR) | 12 months | ORR is defined as the proportion of participants who have a partial response (PR) or critical response (CR) |
| Duration of Response (DoR) | 12 months | DOR is defined as time from date of initial documentation of a response (PR or CR) to date of first documented evidence of progressive disease (PD) |
| Disease Control Rate (DCR) | 12 months | DCR is defined as the proportion of participants who have a partial response (PR), critical response (CR), or disease stable (SD) |
| Progression-Free Survival (PFS) | 12 months | Defined as the duration from the start of treatment until tumor progression or death of any cause. |
| Peak Plasma Concentration (Cmax) of HCB101 | 12 months | Peak Plasma Concentration (Cmax) of HCB101 following single and repeated IV doses of HCB101 at different dose levels. |
| Area under the plasma concentration versus time curve (AUC) of HCB101 | 12 months | Area under the plasma concentration versus time curve (AUC) of HCB101 |
| Time to maximum drug concentration in plasma (Tmax) of HCB101 | 12 months | Time to maximum drug concentration in plasma (Tmax) of HCB101 following single and repeated IV doses of HCB101 at different dose levels. |
| Terminal elimination half-life (t1/2) of HCB101 | 12 months | Terminal elimination half-life (t1/2) of HCB101 following single and repeated IV doses of HCB101 at different dose levels. |
Countries
China
Outcome results
None listed