Phase Ib/IIa, Open-label, Multicenter, Dose Escalation, and Dose Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of HCB101 in Combination With Multiple Agents in Subjects With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- HCB101
- Conditions
- Solid Cancer
- Sponsor
- FBD Biologics Limited
- Enrollment
- 500
- Locations
- 1
- Primary Endpoint
- Number/incidence and percentage of subjects with adverse events.
- Status
- Active, not recruiting
- Last Updated
- 2 months ago
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects are able to understand and willing to provide signed informed consent.
- •Male and female subjects of ≥18 years of age, inclusive, at the time of signing the informed consent.
- •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:
- •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
- •With a known history of hypersensitivity to any components of the study intervention.
- •Prior/Concomitant Therapy/Treatment:
- •Subjects who have undergone major surgery or radical radiotherapy within 28 days before the first dose of study intervention.
- •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.
- •Subjects who have used a radioactive drug (Strontium, Samarium, etc.) within 56 days before the first dose of the study intervention.
- •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.
- •Subjects who have received any treatment targeting the CD47 or SIRPα pathway.
- •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.
Arms & Interventions
Cohort 1: HCB101+Trastuzumab+Pertuzumab+CAPEOX
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;
Intervention: HCB101
Cohort 6b: HCB101 + Pembrolizumab + Cetuximab
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, QW
Intervention: HCB101
Cohort 1: HCB101+Trastuzumab+Pertuzumab+CAPEOX
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;
Intervention: Trastuzumab
Cohort 1: HCB101+Trastuzumab+Pertuzumab+CAPEOX
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;
Intervention: Pertuzumab
Cohort 1: HCB101+Trastuzumab+Pertuzumab+CAPEOX
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;
Intervention: Oxaliplatin
Cohort 1: HCB101+Trastuzumab+Pertuzumab+CAPEOX
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;
Intervention: Capecitabine
Cohort 2: HCB101+Ramucirumab+Paclitaxel
HCB101: QW 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;
Intervention: HCB101
Cohort 2: HCB101+Ramucirumab+Paclitaxel
HCB101: QW 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;
Intervention: Ramucirumab
Cohort 2: HCB101+Ramucirumab+Paclitaxel
HCB101: QW 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;
Intervention: Paclitaxel
Cohort 3a: HCB101 + Bevacizumab + FOLFIRI/ mFOLFOX6
HCB101: QW Bevacizumab 5 mg/kg IV on D1, Q2W FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: HCB101
Cohort 3a: HCB101 + Bevacizumab + FOLFIRI/ mFOLFOX6
HCB101: QW Bevacizumab 5 mg/kg IV on D1, Q2W FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Oxaliplatin
Cohort 3a: HCB101 + Bevacizumab + FOLFIRI/ mFOLFOX6
HCB101: QW Bevacizumab 5 mg/kg IV on D1, Q2W FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Bevacizumab
Cohort 3a: HCB101 + Bevacizumab + FOLFIRI/ mFOLFOX6
HCB101: QW Bevacizumab 5 mg/kg IV on D1, Q2W FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Irinotecan
Cohort 3a: HCB101 + Bevacizumab + FOLFIRI/ mFOLFOX6
HCB101: QW Bevacizumab 5 mg/kg IV on D1, Q2W FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Leucovorin
Cohort 6b: HCB101 + Pembrolizumab + Cetuximab
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, QW
Intervention: Cetuximab
Cohort 3a: HCB101 + Bevacizumab + FOLFIRI/ mFOLFOX6
HCB101: QW Bevacizumab 5 mg/kg IV on D1, Q2W FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: 5-FU
Cohort 3a: HCB101 + Bevacizumab + FOLFIRI/ mFOLFOX6
HCB101: QW Bevacizumab 5 mg/kg IV on D1, Q2W FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Pembrolizumab
Cohort 3b: HCB101 + Cetuximab + FOLFIRI/ mFOLFOX6
HCB101: QW Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, weekly FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: HCB101
Cohort 3b: HCB101 + Cetuximab + FOLFIRI/ mFOLFOX6
HCB101: QW Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, weekly FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Oxaliplatin
Cohort 3b: HCB101 + Cetuximab + FOLFIRI/ mFOLFOX6
HCB101: QW Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, weekly FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Cetuximab
Cohort 3b: HCB101 + Cetuximab + FOLFIRI/ mFOLFOX6
HCB101: QW Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, weekly FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Irinotecan
Cohort 3b: HCB101 + Cetuximab + FOLFIRI/ mFOLFOX6
HCB101: QW Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, weekly FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Leucovorin
Cohort 3b: HCB101 + Cetuximab + FOLFIRI/ mFOLFOX6
HCB101: QW Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, weekly FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: 5-FU
Cohort 3c: HCB101 + Ramucirumab + FOLFIRI
HCB101: QW Ramucirumab 8 mg/kg IV on D1 and 15, Q4W FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: HCB101
Cohort 3c: HCB101 + Ramucirumab + FOLFIRI
HCB101: QW Ramucirumab 8 mg/kg IV on D1 and 15, Q4W FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Ramucirumab
Cohort 3c: HCB101 + Ramucirumab + FOLFIRI
HCB101: QW Ramucirumab 8 mg/kg IV on D1 and 15, Q4W FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Irinotecan
Cohort 3c: HCB101 + Ramucirumab + FOLFIRI
HCB101: QW Ramucirumab 8 mg/kg IV on D1 and 15, Q4W FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Leucovorin
Cohort 3c: HCB101 + Ramucirumab + FOLFIRI
HCB101: QW Ramucirumab 8 mg/kg IV on D1 and 15, Q4W FOLFIRI: Irinotecan 180 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: 5-FU
Cohort 3d: HCB101 + mFOLFOX6
HCB101: QW mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: HCB101
Cohort 3d: HCB101 + mFOLFOX6
HCB101: QW mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Oxaliplatin
Cohort 3d: HCB101 + mFOLFOX6
HCB101: QW mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: Leucovorin
Cohort 3d: HCB101 + mFOLFOX6
HCB101: QW mFOLFOX6: Oxaliplatin 85 mg/m2 IV on D1, Q2W Leucovorin 400 mg/m2 IV on D1, Q2W 5-FU 400 mg/m2 IV on D1, then 1200 mg/m2/day on D2 and D3 (total 2400 mg/m2), Q2W
Intervention: 5-FU
Cohort 4: HCB101 + Pembrolizumab/Toripalimab + albumin-bound paclitaxel
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Albumin-bound paclitaxel 100 mg/m2 on D1, 8, 15, Q4W or 125 mg/m2 IV on D1, D8, Q3W
Intervention: HCB101
Cohort 4: HCB101 + Pembrolizumab/Toripalimab + albumin-bound paclitaxel
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Albumin-bound paclitaxel 100 mg/m2 on D1, 8, 15, Q4W or 125 mg/m2 IV on D1, D8, Q3W
Intervention: Toripalimab
Cohort 4: HCB101 + Pembrolizumab/Toripalimab + albumin-bound paclitaxel
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Albumin-bound paclitaxel 100 mg/m2 on D1, 8, 15, Q4W or 125 mg/m2 IV on D1, D8, Q3W
Intervention: Albumin-bound paclitaxel
Cohort 4: HCB101 + Pembrolizumab/Toripalimab + albumin-bound paclitaxel
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Albumin-bound paclitaxel 100 mg/m2 on D1, 8, 15, Q4W or 125 mg/m2 IV on D1, D8, Q3W
Intervention: Pembrolizumab
Cohort 5: HCB101 + Pembrolizumab + CAPEOX
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W Oxaliplatin 130 mg/m2 IV on D1, Q3W Capecitabine 1000 mg/m2 PO BID on D1-14, Q3W
Intervention: HCB101
Cohort 5: HCB101 + Pembrolizumab + CAPEOX
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W Oxaliplatin 130 mg/m2 IV on D1, Q3W Capecitabine 1000 mg/m2 PO BID on D1-14, Q3W
Intervention: Oxaliplatin
Cohort 5: HCB101 + Pembrolizumab + CAPEOX
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W Oxaliplatin 130 mg/m2 IV on D1, Q3W Capecitabine 1000 mg/m2 PO BID on D1-14, Q3W
Intervention: Capecitabine
Cohort 5: HCB101 + Pembrolizumab + CAPEOX
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W Oxaliplatin 130 mg/m2 IV on D1, Q3W Capecitabine 1000 mg/m2 PO BID on D1-14, Q3W
Intervention: Pembrolizumab
Cohort 6a: HCB101 + Pembrolizumab
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W
Intervention: HCB101
Cohort 6a: HCB101 + Pembrolizumab
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W
Intervention: Pembrolizumab
Cohort 6b: HCB101 + Pembrolizumab + Cetuximab
HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, QW
Intervention: Pembrolizumab
Cohort 6c: HCB101 + Cetuximab
HCB101, QW Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, QW
Intervention: HCB101
Cohort 6c: HCB101 + Cetuximab
HCB101, QW Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, QW
Intervention: Cetuximab
Cohort 7: HCB101 + Trastuzumab Deruxtecan
HCB101, QW Trastuzumab Deruxtecan 5.4 mg/kg IV on D1, Q3W
Intervention: HCB101
Cohort 7: HCB101 + Trastuzumab Deruxtecan
HCB101, QW Trastuzumab Deruxtecan 5.4 mg/kg IV on D1, Q3W
Intervention: Trastuzumab deruxtecan
Cohort 8: HCB101 + Atezolizumab/Toripalimab + Bevacizumab
HCB101, QW Atezolizumab 1200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Bevacizumab 15 mg/kg IV on D1, Q3W
Intervention: HCB101
Cohort 8: HCB101 + Atezolizumab/Toripalimab + Bevacizumab
HCB101, QW Atezolizumab 1200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Bevacizumab 15 mg/kg IV on D1, Q3W
Intervention: Bevacizumab
Cohort 8: HCB101 + Atezolizumab/Toripalimab + Bevacizumab
HCB101, QW Atezolizumab 1200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Bevacizumab 15 mg/kg IV on D1, Q3W
Intervention: Toripalimab
Cohort 8: HCB101 + Atezolizumab/Toripalimab + Bevacizumab
HCB101, QW Atezolizumab 1200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Bevacizumab 15 mg/kg IV on D1, Q3W
Intervention: Atezolizumab
Cohort 9: HCB101 + Atezolizumab/Toripalimab + carboplatin + etoposide.
HCB101, QW Atezolizumab 1200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Carboplatin AUC=5, IV on D1, Q3W for 4 cycles Etoposide 100mg/m2, IV on D1, 2, 3, Q3W for 4 cycles
Intervention: HCB101
Cohort 9: HCB101 + Atezolizumab/Toripalimab + carboplatin + etoposide.
HCB101, QW Atezolizumab 1200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Carboplatin AUC=5, IV on D1, Q3W for 4 cycles Etoposide 100mg/m2, IV on D1, 2, 3, Q3W for 4 cycles
Intervention: Toripalimab
Cohort 9: HCB101 + Atezolizumab/Toripalimab + carboplatin + etoposide.
HCB101, QW Atezolizumab 1200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Carboplatin AUC=5, IV on D1, Q3W for 4 cycles Etoposide 100mg/m2, IV on D1, 2, 3, Q3W for 4 cycles
Intervention: Carboplatin (AUC 5)
Cohort 9: HCB101 + Atezolizumab/Toripalimab + carboplatin + etoposide.
HCB101, QW Atezolizumab 1200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Carboplatin AUC=5, IV on D1, Q3W for 4 cycles Etoposide 100mg/m2, IV on D1, 2, 3, Q3W for 4 cycles
Intervention: Etoposide
Cohort 9: HCB101 + Atezolizumab/Toripalimab + carboplatin + etoposide.
HCB101, QW Atezolizumab 1200 mg IV on D1, Q3W or Toripalimab 240 mg IV on D1, Q3W Carboplatin AUC=5, IV on D1, Q3W for 4 cycles Etoposide 100mg/m2, IV on D1, 2, 3, Q3W for 4 cycles
Intervention: Atezolizumab
Outcomes
Primary Outcomes
Number/incidence and percentage of subjects with adverse events.
Time Frame: 12 months
To evaluate the safety and tolerability of HCB101
Number of subjects with Maximal tolerance dose (MTD) of HCB101
Time Frame: 12 months
To evaluate the tolerability of HCB101
Secondary Outcomes
- Overall Rate Response (ORR)(12 months)
- Duration of Response (DoR)(12 months)
- Disease Control Rate (DCR)(12 months)
- Progression-Free Survival (PFS)(12 months)
- Peak Plasma Concentration (Cmax) of HCB101(12 months)
- Area under the plasma concentration versus time curve (AUC) of HCB101(12 months)
- Time to maximum drug concentration in plasma (Tmax) of HCB101(12 months)
- Terminal elimination half-life (t1/2) of HCB101(12 months)