Active, not recruiting
Phase 1/2
Safety and Efficacy of HCB101 in Combination With Multiple Agents in Patients With Advanced Solid Tumors
Condition(s) studied
Solid Cancer
Investigational drug(s) / intervention(s)
HCB101TrastuzumabPertuzumabOxaliplatinCapecitabineRamucirumabPaclitaxelBevacizumabCetuximabIrinotecanLeucovorin5-FUToripalimabAlbumin-bound paclitaxelPembrolizumabCarboplatin (AUC 5)EtoposideAtezolizumabTrastuzumab deruxtecan
HCB101: QW
Trastuzumab: 8 mg/kg IV loading dose on Day 1 of cycle 1, then 6 mg/kg IV every 21 days;
Pertuzumab: 840 mg IV on Day 1, cycled every 21 days;
Oxaliplatin: 130 mg/m2 IV on Day 1, cycled every 21 days
Capecitabine: 1000 mg/m2 PO BID on Days 1-14, Cycled every 21 days
Ramucirumab: 8 mg/kg IV on Days 1 and 15, Cycled every 28 days
Paclitaxel: 80 mg/m2 IV on Days 1, 8, and 15, Cycled every 28 days
Bevacizumab: 5 mg/kg IV on Day 1, Repeat every 2 weeks;
Cetuximab: 400 mg/m2 first infusion, followed by 250 mg/m2 IV weekly;
Irinotecan: 180 mg/m2 IV over 30-90 minutes on Day 1 every 2 weeks
Leucovorin: 400 mg/m2 IV on Day 1 every 2 weeks
5-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
Toripalimab: 240 mg/kg IV on Day 1 Cycled every 21 days
Albumin-bound paclitaxel: 125 mg/m2 IV on day 1 and Day 8 Cycled every 21 days
Pembrolizumab: 200 mg IV day 1; given every 21 days
Carboplatin (AUC 5): AUC=5, IV on D1, Q3W for 4\~6 cycles
Etoposide: 100mg/m2, IV on D1, 2, 3, Q3W for 4\~6 cycles
Atezolizumab: 1200 mg IV on D1, Q3W
Trastuzumab deruxtecan: 5.4 mg/kg IV on D1, Q3W
Study 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).
Eligibility
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.
Primary outcome measure(s)
- 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
Trial sites (1)
| Facility | City | Region | Status |
| Cancer Hospital of Shandong First Medical University |
Jinan |
Shandong |
|
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