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

Phase 1

Recruiting

• Conditions: Solid Cancer
• Interventions: Drug: HCB101; Drug: Trastuzumab; Drug: Ramucirumab; Drug: Toripalimab; Drug: Pertuzumab; Drug: Paclitaxel; Drug: Albumin-bound paclitaxel; Drug: Oxaliplatin; Drug: Pembrolizumab; Drug: Bevacizumab; Drug: Capecitabine; Drug: Gemcitabine; Drug: Cetuximab; Drug: Irinotecan; Drug: Leucovorin; Drug: 5-FU

• Registration Number: NCT06771622
• Lead Sponsor: FBD Biologics Limited

Brief Summary

This is a non-randomized, open-label, dose-escalation, and dose-expansion Phase Ib/IIa study to evaluate the safety, tolerability, PK profile, and preliminary efficacy of HCB101 in combination therapies in subjects with advanced solid tumors. The trial consists of four cohorts, each including a part I of the dose-escalation phase (Phase Ib) and a part II of the dose-expansion phase (Phase IIa).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-08
• Study First Submitted QC: 2025-01-08
• Study First Posted: 2025-01-13
• Study Start: 2025-03-13
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-02
• Last Update Posted: 2025-04-04
• Primary Completion: 2028-01-01
• Study Completion: 2029-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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: HER2 overexpression positive (IHC 3+ or IHC 2+ and evidence of HER2 amplification by FISH), unresectable locally advanced, recurrent, or metastatic gastric cancer, patients must be previously untreated with systemic treatment; Subject that received neoadjuvant chemotherapy with recurrence >6 months from completion of therapy are permitted.
   2. Cohort 2: Unresectable locally advanced, recurrent, or metastatic gastric cancer, progression on or after first-line standard treatment; Prior neoadjuvant or adjuvant therapy can be counted as a line of therapy if the subject progressed on or within 6 months of completing neoadjuvant or adjuvant therapy.
   3. Cohort 3: Advanced or metastatic colorectal cancer, RAS (KRAS, NRAS) gene is wild-type, and no BRAF V600E mutation has been identified, progression on or after first-line standard treatment; Prior neoadjuvant or adjuvant therapy can be counted as a line of therapy if the subject progressed on or within 6 months of completing neoadjuvant or adjuvant therapy.
   4. Cohort 4: Recurrent unresectable (local or regional) or stage IV (M1) triple-negative breast cancer TNBC, whose tumors express PD-L1 with a CPS ≥ 10, patients must be previously untreated with systemic treatment; Subject that received neoadjuvant chemotherapy with recurrence >6 months from completion of therapy are permitted.

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. Subjects who have other malignancies requiring treatment within 2 years before the first dose of study intervention will be excluded, except for radically treated locally curable basal or squamous cell skin cancer and other malignancies that have been treated with no relapse within 2 years.
3. Subjects who have undergone any investigational or approved systemic cancer therapy (including chemotherapy, immunotherapy, hormonal therapy, and herbal/alternative therapies with anti-cancer indications or targeted therapy) within 14 days or 5 half-lives, whichever is longer, before the first dose of the 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HCB101+Trastuzumab+Pertuzumab+XELOX	Trastuzumab	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;
HCB101+Trastuzumab+Pertuzumab+XELOX	Pertuzumab	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;
HCB101+Trastuzumab+Pertuzumab+XELOX	Oxaliplatin	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;
HCB101+Trastuzumab+Pertuzumab+XELOX	Capecitabine	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;
HCB101+Ramucirumab+Paclitaxel	HCB101	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;
HCB101+Ramucirumab+Paclitaxel	Ramucirumab	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;
HCB101+Ramucirumab+Paclitaxel	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;
HCB101+ Bevacizumab/Cetuximab + FOLFORI/FOLFOX/CAPEOX	Toripalimab	HCB101: QW Bevacizumab: 5 mg/kg IV on Day 1, repeat every 2 weeks; or 7.5 mg/kg IV on Day 1, repeat every 3 weeks; Cetuximab: 400 mg/m2 first infusion, followed by 250 mg/m2 IV, weekly; or 500 mg/m2 IV over 2 hours on Day 1 every 2 weeks; Irinotecan: 180 mg/m2 IV over 30-90 minutes on Day 1, repeat every 2 weeks; Leucovorin: 400 mg/m2 IV on Day 1, repeat every 2 weeks; 5-FU: 400 mg/ m2 IV bolus on Day 1, followed by 1200 mg/m2/day x 2 ;
HCB101+ Bevacizumab/Cetuximab + FOLFORI/FOLFOX/CAPEOX	Albumin-bound paclitaxel	HCB101: QW Bevacizumab: 5 mg/kg IV on Day 1, repeat every 2 weeks; or 7.5 mg/kg IV on Day 1, repeat every 3 weeks; Cetuximab: 400 mg/m2 first infusion, followed by 250 mg/m2 IV, weekly; or 500 mg/m2 IV over 2 hours on Day 1 every 2 weeks; Irinotecan: 180 mg/m2 IV over 30-90 minutes on Day 1, repeat every 2 weeks; Leucovorin: 400 mg/m2 IV on Day 1, repeat every 2 weeks; 5-FU: 400 mg/ m2 IV bolus on Day 1, followed by 1200 mg/m2/day x 2 ;
HCB101+ Bevacizumab/Cetuximab + FOLFORI/FOLFOX/CAPEOX	Pembrolizumab	HCB101: QW Bevacizumab: 5 mg/kg IV on Day 1, repeat every 2 weeks; or 7.5 mg/kg IV on Day 1, repeat every 3 weeks; Cetuximab: 400 mg/m2 first infusion, followed by 250 mg/m2 IV, weekly; or 500 mg/m2 IV over 2 hours on Day 1 every 2 weeks; Irinotecan: 180 mg/m2 IV over 30-90 minutes on Day 1, repeat every 2 weeks; Leucovorin: 400 mg/m2 IV on Day 1, repeat every 2 weeks; 5-FU: 400 mg/ m2 IV bolus on Day 1, followed by 1200 mg/m2/day x 2 ;
HCB101+ Bevacizumab/Cetuximab + FOLFORI/FOLFOX/CAPEOX	Gemcitabine	HCB101: QW Bevacizumab: 5 mg/kg IV on Day 1, repeat every 2 weeks; or 7.5 mg/kg IV on Day 1, repeat every 3 weeks; Cetuximab: 400 mg/m2 first infusion, followed by 250 mg/m2 IV, weekly; or 500 mg/m2 IV over 2 hours on Day 1 every 2 weeks; Irinotecan: 180 mg/m2 IV over 30-90 minutes on Day 1, repeat every 2 weeks; Leucovorin: 400 mg/m2 IV on Day 1, repeat every 2 weeks; 5-FU: 400 mg/ m2 IV bolus on Day 1, followed by 1200 mg/m2/day x 2 ;
HCB101+ Toripalimab/Pembrolizumab + Albumin-bound paclitaxel/chemotherapy	Capecitabine	HCB101: QW Pembrolizumab: 200 mg IV day 1; given every 21 days; Toripalimab: 240 mg/kg IV on Day 1, cycled every 21 days; Albumin-bound paclitaxel: 100 mg/m2 days 1, 8, 15; given every 28 days); or 125 mg/m2 IV on day 1 and Day 8, cycled every 21 days; Paclitaxel: 90 mg/m2 IV days 1, 8, 15; given every 28 days; Gemcitabine: 1000 mg/m2 IV days 1 and 8, given every 21 days; Carboplatin: AUC 2 IV days 1 and 8, given every 21 days;
HCB101+ Toripalimab/Pembrolizumab + Albumin-bound paclitaxel/chemotherapy	Bevacizumab	HCB101: QW Pembrolizumab: 200 mg IV day 1; given every 21 days; Toripalimab: 240 mg/kg IV on Day 1, cycled every 21 days; Albumin-bound paclitaxel: 100 mg/m2 days 1, 8, 15; given every 28 days); or 125 mg/m2 IV on day 1 and Day 8, cycled every 21 days; Paclitaxel: 90 mg/m2 IV days 1, 8, 15; given every 28 days; Gemcitabine: 1000 mg/m2 IV days 1 and 8, given every 21 days; Carboplatin: AUC 2 IV days 1 and 8, given every 21 days;
HCB101+ Toripalimab/Pembrolizumab + Albumin-bound paclitaxel/chemotherapy	Cetuximab	HCB101: QW Pembrolizumab: 200 mg IV day 1; given every 21 days; Toripalimab: 240 mg/kg IV on Day 1, cycled every 21 days; Albumin-bound paclitaxel: 100 mg/m2 days 1, 8, 15; given every 28 days); or 125 mg/m2 IV on day 1 and Day 8, cycled every 21 days; Paclitaxel: 90 mg/m2 IV days 1, 8, 15; given every 28 days; Gemcitabine: 1000 mg/m2 IV days 1 and 8, given every 21 days; Carboplatin: AUC 2 IV days 1 and 8, given every 21 days;
HCB101+ Toripalimab/Pembrolizumab + Albumin-bound paclitaxel/chemotherapy	Oxaliplatin	HCB101: QW Pembrolizumab: 200 mg IV day 1; given every 21 days; Toripalimab: 240 mg/kg IV on Day 1, cycled every 21 days; Albumin-bound paclitaxel: 100 mg/m2 days 1, 8, 15; given every 28 days); or 125 mg/m2 IV on day 1 and Day 8, cycled every 21 days; Paclitaxel: 90 mg/m2 IV days 1, 8, 15; given every 28 days; Gemcitabine: 1000 mg/m2 IV days 1 and 8, given every 21 days; Carboplatin: AUC 2 IV days 1 and 8, given every 21 days;
HCB101+ Toripalimab/Pembrolizumab + Albumin-bound paclitaxel/chemotherapy	Irinotecan	HCB101: QW Pembrolizumab: 200 mg IV day 1; given every 21 days; Toripalimab: 240 mg/kg IV on Day 1, cycled every 21 days; Albumin-bound paclitaxel: 100 mg/m2 days 1, 8, 15; given every 28 days); or 125 mg/m2 IV on day 1 and Day 8, cycled every 21 days; Paclitaxel: 90 mg/m2 IV days 1, 8, 15; given every 28 days; Gemcitabine: 1000 mg/m2 IV days 1 and 8, given every 21 days; Carboplatin: AUC 2 IV days 1 and 8, given every 21 days;
HCB101+ Toripalimab/Pembrolizumab + Albumin-bound paclitaxel/chemotherapy	Leucovorin	HCB101: QW Pembrolizumab: 200 mg IV day 1; given every 21 days; Toripalimab: 240 mg/kg IV on Day 1, cycled every 21 days; Albumin-bound paclitaxel: 100 mg/m2 days 1, 8, 15; given every 28 days); or 125 mg/m2 IV on day 1 and Day 8, cycled every 21 days; Paclitaxel: 90 mg/m2 IV days 1, 8, 15; given every 28 days; Gemcitabine: 1000 mg/m2 IV days 1 and 8, given every 21 days; Carboplatin: AUC 2 IV days 1 and 8, given every 21 days;
HCB101+ Toripalimab/Pembrolizumab + Albumin-bound paclitaxel/chemotherapy	5-FU	HCB101: QW Pembrolizumab: 200 mg IV day 1; given every 21 days; Toripalimab: 240 mg/kg IV on Day 1, cycled every 21 days; Albumin-bound paclitaxel: 100 mg/m2 days 1, 8, 15; given every 28 days); or 125 mg/m2 IV on day 1 and Day 8, cycled every 21 days; Paclitaxel: 90 mg/m2 IV days 1, 8, 15; given every 28 days; Gemcitabine: 1000 mg/m2 IV days 1 and 8, given every 21 days; Carboplatin: AUC 2 IV days 1 and 8, given every 21 days;
HCB101+Trastuzumab+Pertuzumab+XELOX	HCB101	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;
HCB101+ Toripalimab/Pembrolizumab + Albumin-bound paclitaxel/chemotherapy	HCB101	HCB101: QW Pembrolizumab: 200 mg IV day 1; given every 21 days; Toripalimab: 240 mg/kg IV on Day 1, cycled every 21 days; Albumin-bound paclitaxel: 100 mg/m2 days 1, 8, 15; given every 28 days); or 125 mg/m2 IV on day 1 and Day 8, cycled every 21 days; Paclitaxel: 90 mg/m2 IV days 1, 8, 15; given every 28 days; Gemcitabine: 1000 mg/m2 IV days 1 and 8, given every 21 days; Carboplatin: AUC 2 IV days 1 and 8, given every 21 days;
HCB101+ Bevacizumab/Cetuximab + FOLFORI/FOLFOX/CAPEOX	HCB101	HCB101: QW Bevacizumab: 5 mg/kg IV on Day 1, repeat every 2 weeks; or 7.5 mg/kg IV on Day 1, repeat every 3 weeks; Cetuximab: 400 mg/m2 first infusion, followed by 250 mg/m2 IV, weekly; or 500 mg/m2 IV over 2 hours on Day 1 every 2 weeks; Irinotecan: 180 mg/m2 IV over 30-90 minutes on Day 1, repeat every 2 weeks; Leucovorin: 400 mg/m2 IV on Day 1, repeat every 2 weeks; 5-FU: 400 mg/ m2 IV bolus on Day 1, followed by 1200 mg/m2/day x 2 ;

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Cancer Hospital of Shandong First Medical University; 🇨🇳 Jinan, Shandong, China