Safety and Efficacy of HCB101 in Combination With Multiple Agents in Patients With Advanced Solid Tumors

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Cancer
• Intervention / Treatment: Drug: HCB101; Drug: Trastuzumab; Drug: Pertuzumab; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Ramucirumab; Drug: Paclitaxel; Drug: Toripalimab; Drug: Albumin-bound paclitaxel; Drug: Pembrolizumab; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-FU; Drug: Bevacizumab; Drug: Cetuximab; Drug: Trastuzumab deruxtecan; Drug: Atezolizumab; Drug: Carboplatin (AUC 5); Drug: Etoposide

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China
      • Cancer Hospital of Shandong First Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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;	Drug: HCB101; QW; Drug: Trastuzumab; 8 mg/kg IV loading dose on Day 1 of cycle 1, then 6 mg/kg IV every 21 days; Drug: Pertuzumab; 840 mg IV on Day 1, cycled every 21 days; Drug: Oxaliplatin; 130 mg/m2 IV on Day 1, cycled every 21 days; Drug: Capecitabine; 1000 mg/m2 PO BID on Days 1-14, Cycled every 21 days
Experimental: 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;	Drug: HCB101; QW; Drug: Ramucirumab; 8 mg/kg IV on Days 1 and 15, Cycled every 28 days; Drug: Paclitaxel; 80 mg/m2 IV on Days 1, 8, and 15, Cycled every 28 days
Experimental: 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	Drug: HCB101; QW; Drug: Oxaliplatin; 130 mg/m2 IV on Day 1, cycled every 21 days; Drug: Pembrolizumab; 200 mg IV day 1; given every 21 days; Drug: Irinotecan; 180 mg/m2 IV over 30-90 minutes on Day 1 every 2 weeks; Drug: Leucovorin; 400 mg/m2 IV on Day 1 every 2 weeks; Drug: 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; Drug: Bevacizumab; 5 mg/kg IV on Day 1, Repeat every 2 weeks;
Experimental: 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	Drug: HCB101; QW; Drug: Oxaliplatin; 130 mg/m2 IV on Day 1, cycled every 21 days; Drug: Irinotecan; 180 mg/m2 IV over 30-90 minutes on Day 1 every 2 weeks; Drug: Leucovorin; 400 mg/m2 IV on Day 1 every 2 weeks; Drug: 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; Drug: Cetuximab; 400 mg/m2 first infusion, followed by 250 mg/m2 IV weekly;
Experimental: 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	Drug: HCB101; QW; Drug: Ramucirumab; 8 mg/kg IV on Days 1 and 15, Cycled every 28 days; Drug: Irinotecan; 180 mg/m2 IV over 30-90 minutes on Day 1 every 2 weeks; Drug: Leucovorin; 400 mg/m2 IV on Day 1 every 2 weeks; Drug: 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
Experimental: 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	Drug: HCB101; QW; Drug: Oxaliplatin; 130 mg/m2 IV on Day 1, cycled every 21 days; Drug: Leucovorin; 400 mg/m2 IV on Day 1 every 2 weeks; Drug: 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
Experimental: 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	Drug: HCB101; QW; Drug: Toripalimab; 240 mg/kg IV on Day 1 Cycled every 21 days; Drug: Albumin-bound paclitaxel; 125 mg/m2 IV on day 1 and Day 8 Cycled every 21 days; Drug: Pembrolizumab; 200 mg IV day 1; given every 21 days
Experimental: 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	Drug: HCB101; QW; Drug: Oxaliplatin; 130 mg/m2 IV on Day 1, cycled every 21 days; Drug: Capecitabine; 1000 mg/m2 PO BID on Days 1-14, Cycled every 21 days; Drug: Pembrolizumab; 200 mg IV day 1; given every 21 days
Experimental: Cohort 6a: HCB101 + Pembrolizumab; HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W	Drug: HCB101; QW; Drug: Pembrolizumab; 200 mg IV day 1; given every 21 days
Experimental: 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	Drug: HCB101; QW; Drug: Pembrolizumab; 200 mg IV day 1; given every 21 days; Drug: Cetuximab; 400 mg/m2 first infusion, followed by 250 mg/m2 IV weekly;
Experimental: Cohort 6c: HCB101 + Cetuximab; HCB101, QW Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, QW	Drug: HCB101; QW; Drug: Cetuximab; 400 mg/m2 first infusion, followed by 250 mg/m2 IV weekly;
Experimental: Cohort 7: HCB101 + Trastuzumab Deruxtecan; HCB101, QW Trastuzumab Deruxtecan 5.4 mg/kg IV on D1, Q3W	Drug: HCB101; QW; Drug: Trastuzumab deruxtecan; 5.4 mg/kg IV on D1, Q3W
Experimental: 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	Drug: HCB101; QW; Drug: Toripalimab; 240 mg/kg IV on Day 1 Cycled every 21 days; Drug: Bevacizumab; 5 mg/kg IV on Day 1, Repeat every 2 weeks; Drug: Atezolizumab; 1200 mg IV on D1, Q3W
Experimental: 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	Drug: HCB101; QW; Drug: Toripalimab; 240 mg/kg IV on Day 1 Cycled every 21 days; Drug: Atezolizumab; 1200 mg IV on D1, Q3W; Drug: Carboplatin (AUC 5); AUC=5, IV on D1, Q3W for 4~6 cycles; Drug: Etoposide; 100mg/m2, IV on D1, 2, 3, Q3W for 4~6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number/incidence and percentage of subjects with adverse events.	To evaluate the safety and tolerability of HCB101	12 months
Number of subjects with Maximal tolerance dose (MTD) of HCB101	To evaluate the tolerability of HCB101	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Rate Response (ORR)	ORR is defined as the proportion of participants who have a partial response (PR) or critical response (CR)	12 months
Duration of Response (DoR)	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)	12 months
Disease Control Rate (DCR)	DCR is defined as the proportion of participants who have a partial response (PR), critical response (CR), or disease stable (SD)	12 months
Progression-Free Survival (PFS)	Defined as the duration from the start of treatment until tumor progression or death of any cause.	12 months
Peak Plasma Concentration (Cmax) of HCB101	Peak Plasma Concentration (Cmax) of HCB101 following single and repeated IV doses of HCB101 at different dose levels.	12 months
Time to maximum drug concentration in plasma (Tmax) of HCB101	Time to maximum drug concentration in plasma (Tmax) of HCB101 following single and repeated IV doses of HCB101 at different dose levels.	12 months
Terminal elimination half-life (t1/2) of HCB101	Terminal elimination half-life (t1/2) of HCB101 following single and repeated IV doses of HCB101 at different dose levels.	12 months
Area under the plasma concentration versus time curve (AUC) of HCB101	Area under the plasma concentration versus time curve (AUC) of HCB101	12 months

Collaborators and Investigators

• Sponsor: FBD Biologics Limited

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: January 8, 2025
• First Submitted That Met QC Criteria: January 8, 2025
• First Posted (Actual): January 13, 2025

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Carbohydrates; Camptothecin; Alkaloids; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Deoxyribonucleosides; Albumins; Trastuzumab; Capecitabine; Oxaliplatin; Bevacizumab; Irinotecan; Albumin-Bound Paclitaxel; Cetuximab; Ramucirumab; Fluorouracil; Etoposide; Carboplatin; Leucovorin; Paclitaxel; toripalimab; pertuzumab; pembrolizumab; atezolizumab; trastuzumab deruxtecan
• Other Study ID Numbers: HCB101-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No