GB268 Monotherapy or Combination Therapy for Locally Advanced/Metastatic Breast Cancer (Phase Ib/Ⅱ)

NCT07738341 | Not Yet Recruiting Phase 1

• 1 other identifier: GB268-201
• Study Type: interventional
• Target: 270
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase Ib/II, open-label, multi-cohort, multi-center study to evaluate the safety, tolerability, and preliminary anti-tumor activity of GB268, a biological product, as monotherapy or in combination with other therapies in patients with locally advanced unresectable or metastatic breast cancer.

Conditions

Breast Cancer (Locally Advanced or Metastatic)

Keywords

GB268; Immunotherapy; PD-1; CTLA-4; VEGF

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicities [DLTs] (Phase Ib)

  Incidence of Dose-Limiting Toxicities \[DLTs\] during the first treatment cycle

  Within 21 days after first dose

• Objective Response Rate [ORR] (Phase II)

  ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on Investigator per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]

  Up to approximately 2 years

Secondary Outcomes (10)

• Number of participants with adverse events [AEs] (Phase Ib and Phase II)

  Up to approximately 2 years

• Objective Response Rate [ORR] (Phase Ib)

  Up to approximately 2 years

• Duration of Response [DOR] (Phase Ib and Phase II)

  Up to approximately 2 years

• Overall Survival [OS] (Phase Ib and Phase II)

  Up to approximately 2 years

• Disease Control Rate [DCR] (Phase Ib and Phase II)

  Up to approximately 2 years

Study Arms (5)

Cohort A (GB268 + Sacituzumab Tirumotecan)

EXPERIMENTAL

GB268 (10 or 20 mg/kg Q3W intravenously \[IV\], dose selected by Safety Review Committee \[SRC\]) + Sacituzumab Tirumotecan 5 mg/kg once every 2 weeks \[Q2W\] IV. For participants with locally advanced/metastatic Triple-Negative Breast Cancer \[TNBC\] with no prior systemic therapy for advanced disease; no prior Trop-2 Antibody-Drug Conjugate \[ADC\].

Drug: GB268; Drug: Sacituzumab Tirumotecan

Cohort B (GB268 + Nab-Paclitaxel)

EXPERIMENTAL

GB268 (10 or 20 mg/kg Q3W IV) + Nab-Paclitaxel 260 mg/m² Day 1 Q3W IV. For participants with locally advanced/metastatic TNBC with no prior systemic therapy for advanced disease; prior adjuvant/neoadjuvant taxane allowed only if recurrence ≥12 months after last taxane dose.

Drug: GB268; Drug: Nab-Paclitaxel

Cohort E (GB268+ Datopotamab Deruxtecan)

EXPERIMENTAL

GB268 (10 or 20 mg/kg Q3W IV) + Datopotamab Deruxtecan 6 mg/kg Day 1 Q3W IV. For participants with HR+/HER2- breast cancer who have received at least 1 line of endocrine therapy, CDK4/6i, and at least 1 line of systemic chemotherapy in the advanced setting; no prior Trop-2 ADC.

Drug: GB268; Drug: Datopotamab Deruxtecan (Dato-DXd)

Cohort F (GB268 + Nab-Paclitaxel)

EXPERIMENTAL

GB268 (10 or 20 mg/kg Q3W IV) + Nab-Paclitaxel 260 mg/m² Day 1 Q3W IV. For participants with HR+/HER2- breast cancer with disease progression after ≥1 line of endocrine therapy and CDK4/6i, with primary or secondary endocrine resistance; prior adjuvant/neoadjuvant taxane allowed only if recurrence ≥12 months after last taxane dose.

Drug: GB268; Drug: Nab-Paclitaxel

Cohort G (GB268 monotherapy)

EXPERIMENTAL

GB268 monotherapy (dose not exceeding 30 mg/kg Q3W, selected by SRC) IV. For participants with HR+/HER2- breast cancer who have received prior CDK4/6i and endocrine therapy in any setting, and a TROP2 or HER2 ADC in the advanced setting.

Drug: GB268

Interventions

GB268 DRUG

GB268 is a tri-specific antibody targeting PD-1, CTLA-4, and VEGF. It is designed to block immune checkpoints (PD-1/CTLA-4) to enhance T-cell-mediated anti-tumor immune responses and simultaneously inhibit VEGF-mediated tumor angiogenesis

Cohort A (GB268 + Sacituzumab Tirumotecan); Cohort B (GB268 + Nab-Paclitaxel); Cohort E (GB268+ Datopotamab Deruxtecan); Cohort F (GB268 + Nab-Paclitaxel); Cohort G (GB268 monotherapy)

Nab-Paclitaxel DRUG

Nab-Paclitaxel is a microtubule-stabilizing agent formulated as albumin-bound nanoparticles for IV administration.

Cohort B (GB268 + Nab-Paclitaxel); Cohort F (GB268 + Nab-Paclitaxel)

Datopotamab Deruxtecan (Dato-DXd) DRUG

Datopotamab Deruxtecan is an ADC targeting Trop-2, consisting of a monoclonal antibody linked to a topoisomerase I inhibitor payload.

Cohort E (GB268+ Datopotamab Deruxtecan)

Sacituzumab Tirumotecan DRUG

A Trop-2-directed Antibody-Drug Conjugate \[ADC\] consisting of a humanized anti-Trop-2 monoclonal antibody covalently linked to a topoisomerase I inhibitor payload.

Cohort A (GB268 + Sacituzumab Tirumotecan)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years, male or female.
• Histologically confirmed locally advanced unresectable or metastatic breast cancer (Triple-Negative Breast Cancer \[TNBC\] or Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative \[HR+/HER2-\]).
• At least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\].
• No prior treatment with any immune checkpoint inhibitor (e.g., anti-Programmed Death-1 \[PD-1\], anti-Programmed Death-Ligand 1 \[PD-L1\], anti-Cytotoxic T-Lymphocyte-Associated Protein 4 \[CTLA-4\]) or Programmed Death-1/Vascular Endothelial Growth Factor \[PD-1/VEGF\] bispecific antibody, except for adjuvant therapy if relapse occurred ≥12 months after discontinuation.
• Assessed by the investigator as suitable for the assigned combination therapy.
• Eastern Cooperative Oncology Group \[ECOG\] performance status 0 or 1.
• Life expectancy ≥ 3 months.
• Adequate organ function (within 14 days before first dose, without transfusion or Granulocyte Colony-Stimulating Factor \[G-CSF\] support): Hemoglobin ≥ 9 g/dL, Absolute Neutrophil Count \[ANC\] ≥ 1.5×10\^9/L, Platelets ≥ 100×10\^9/L; Aspartate Aminotransferase \[AST\] and Alanine Aminotransferase \[ALT\] ≤ 3×Upper Limit of Normal \[ULN\] (≤5×ULN if liver metastases); Alkaline Phosphatase \[ALP\] ≤ 2.5×ULN (≤5×ULN if bone or liver metastases); Total Bilirubin ≤ 1.5×ULN (≤3×ULN for Gilbert's Syndrome); Serum Creatinine ≤ 1.5×ULN or Creatinine Clearance ≥ 50 mL/min (Cockcroft-Gault formula); Urine protein dipstick ≤ 1+ (if ≥2+, 24-hour urine protein quantification \< 1 g); Coagulation function: International Normalized Ratio \[INR\] or activated Partial Thromboplastin Time \[aPTT\] ≤ 1.5×ULN (for patients not on anticoagulation therapy).
• Provide a Formalin-Fixed Paraffin-Embedded \[FFPE\] tumor tissue sample for biomarker testing.
• Effective contraception for fertile participants.

You may not qualify if:

• Prior anti-cancer therapy within specified washout periods.
• Systemic immunosuppressive therapy within 2 weeks before first dose.
• Major surgery or significant traumatic injury within 4 weeks before first dose.
• Unresolved toxicity from prior therapy \> Grade 1 (except alopecia or Grade ≤2 hypothyroidism stable on hormone replacement).
• Prior immune-related adverse events \[irAEs\] ≥ Grade 3 leading to treatment discontinuation.
• Active Central Nervous System \[CNS\] metastases (except stable asymptomatic lesions).
• History of other malignancies within 3 years (except cured non-melanoma skin cancer or carcinoma in situ).
• Uncontrolled pleural effusion or ascites requiring repeated drainage.
• Clinically significant cardiovascular disease (e.g., myocardial infarction, unstable angina, stroke within 6 months; QTcF prolongation; New York Heart Association \[NYHA\] Class II-IV heart failure; pericarditis/myocarditis).
• History of Interstitial Lung Disease \[ILD\] or non-infectious pneumonitis requiring steroids.
• Active or history of autoimmune disease requiring systemic treatment in the past 2 years.
• History of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea).
• History of hypertensive crisis or hypertensive encephalopathy.
• Severe coagulation disorders or significant bleeding risk (e.g., severe vascular disease, hemoptysis, intracranial/spinal hemorrhage, tumor invading major vessels).
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess.

Sponsors & Collaborators

• Eddingpharm (Zhuhai) Co., Ltd.: lead

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Binghe Xu

CONTACT

86 10 67781331; xubinghe@medmail.com.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2026
• First Posted: July 31, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2030
• Last Updated: July 31, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share