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

FBD Biologics

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Solid Cancer

Treatments: Drug: Trastuzumab deruxtecan; Drug: Trastuzumab; Drug: Carboplatin (AUC 5); Drug: Leucovorin; Drug: Capecitabine; Drug: Oxaliplatin; Drug: Pembrolizumab; Drug: Cetuximab; Drug: 5-FU; Drug: Ramucirumab; Drug: Paclitaxel; Drug: Irinotecan; Drug: Pertuzumab; Drug: Toripalimab; Drug: Etoposide; Drug: Atezolizumab; Drug: Albumin-bound paclitaxel; Drug: HCB101; Drug: Bevacizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06771622

HCB101-201

Details and patient eligibility

About

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).

Enrollment: 500 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

500 participants in 14 patient groups

Cohort 1: HCB101+Trastuzumab+Pertuzumab+CAPEOX

Experimental group

Description:

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;

Treatment:

Drug: HCB101

Drug: Pertuzumab

Drug: Capecitabine

Drug: Oxaliplatin

Drug: Trastuzumab

Cohort 2: HCB101+Ramucirumab+Paclitaxel

Experimental group

Description:

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;

Treatment:

Drug: HCB101

Drug: Paclitaxel

Drug: Ramucirumab

Cohort 3a: HCB101 + Bevacizumab + FOLFIRI/ mFOLFOX6

Experimental group

Description:

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

Treatment:

Drug: Bevacizumab

Drug: HCB101

Drug: Irinotecan

Drug: 5-FU

Drug: Pembrolizumab

Drug: Oxaliplatin

Drug: Leucovorin

Cohort 3b: HCB101 + Cetuximab + FOLFIRI/ mFOLFOX6

Experimental group

Description:

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

Treatment:

Drug: HCB101

Drug: Irinotecan

Drug: 5-FU

Drug: Cetuximab

Drug: Oxaliplatin

Drug: Leucovorin

Cohort 3c: HCB101 + Ramucirumab + FOLFIRI

Experimental group

Description:

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

Treatment:

Drug: HCB101

Drug: Irinotecan

Drug: Ramucirumab

Drug: 5-FU

Drug: Leucovorin

Cohort 3d: HCB101 + mFOLFOX6

Experimental group

Description:

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

Treatment:

Drug: HCB101

Drug: 5-FU

Drug: Oxaliplatin

Drug: Leucovorin

Cohort 4: HCB101 + Pembrolizumab/Toripalimab + albumin-bound paclitaxel

Experimental group

Description:

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

Treatment:

Drug: HCB101

Drug: Albumin-bound paclitaxel

Drug: Toripalimab

Drug: Pembrolizumab

Cohort 5: HCB101 + Pembrolizumab + CAPEOX

Experimental group

Description:

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

Treatment:

Drug: HCB101

Drug: Pembrolizumab

Drug: Capecitabine

Drug: Oxaliplatin

Cohort 6a: HCB101 + Pembrolizumab

Experimental group

Description:

HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W

Treatment:

Drug: HCB101

Drug: Pembrolizumab

Cohort 6b: HCB101 + Pembrolizumab + Cetuximab

Experimental group

Description:

HCB101, QW Pembrolizumab 200 mg IV on D1, Q3W Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, QW

Treatment:

Drug: HCB101

Drug: Cetuximab

Drug: Pembrolizumab

Cohort 6c: HCB101 + Cetuximab

Experimental group

Description:

HCB101, QW Cetuximab 400 mg/m2 IV on D1, then 250 mg/m2, QW

Treatment:

Drug: HCB101

Drug: Cetuximab

Cohort 7: HCB101 + Trastuzumab Deruxtecan

Experimental group

Description:

HCB101, QW Trastuzumab Deruxtecan 5.4 mg/kg IV on D1, Q3W

Treatment:

Drug: HCB101

Drug: Trastuzumab deruxtecan

Cohort 8: HCB101 + Atezolizumab/Toripalimab + Bevacizumab

Experimental group

Description:

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

Treatment:

Drug: Bevacizumab

Drug: HCB101

Drug: Atezolizumab

Drug: Toripalimab

Cohort 9: HCB101 + Atezolizumab/Toripalimab + carboplatin + etoposide.

Experimental group

Description:

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

Treatment:

Drug: HCB101

Drug: Atezolizumab

Drug: Etoposide

Drug: Toripalimab

Drug: Carboplatin (AUC 5)