Study of IBI3005 Combination Therapy in Participants With Unresectable, Locally Advanced or Metastatic Solid Tumors

Official title

A Phase Ib/II Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of IBI3005 Combination Therapy in Participants With Advanced Solid Tumors

Overview

To evaluate the safety and tolerability of IBI3005 combination therapy in participants with advanced solid tumors; to evaluate the antitumor activity of IBI3005 combination therapy in participants with advanced solid tumors.

Interventions

• Drug IBI3005
  Bispecific Monoclonal Antibody-Camptothecin Derivative Conjugate for Injection (R \& D code: IBI3005)
• Drug Sintilimab
  Anti-PD-1 Monoclonal Antibody
• Drug Bevacizumab biosimilar
  Recombinant humanized anti-VEGF monoclonal antibody
• Drug Limertinib
  Third-generation EGFR-TKI
• Drug Osimertinib
  Third-generation EGFR-TKI
• Drug Carboplatin
  Second-generation platinum-based chemotherapy drugs

Primary outcome measures

• Number of subjects with adverse events [Time frame: Up to 3 years]
• Number of subjects with treatment emergent adverse events [Time frame: Up to 3 weeks]
• Number of subjects with adverse events of special interest [Time frame: Up to 3 years]
• Number of subjects with serious adverse events [Time frame: Up to 3 years]
• Dose limiting toxicities (DLTs) [Time frame: Up to 3 weeks]
• Number of subjects with clinically significant changes in laboratory tests results [Time frame: Up to 3 years]
• Number of subjects with clinically significant changes in physical examination results [Time frame: Up to 3 years]
• Number of subjects with clinically significant changes in vital signs [Time frame: Up to 3 years]
• Objective Response Rate, (ORR） [Time frame: Up to 3 years]
• duration of response (DCR) [Time frame: Up to 3 years]

Secondary outcome measures (7)

• area under the curve (AUC) [Time frame: Up to 3 years]
• maximum concentration (Cmax) [Time frame: Up to 3 years]
• time to maximum concentration (Tmax) [Time frame: Up to 3 years]
• clearance (CL) [Time frame: Up to 3 years]
• apparent volume of distribution (V) [Time frame: Up to 3 years]
• half-life (t1/2) [Time frame: Up to 3 years]
• anti-drug antibody (ADA) [Time frame: Up to 3 years]

Eligibility criteria

Inclusion criteria

• Has signed a written informed consent form (ICF) and is able to comply with the scheduled study visits and related procedures.
• Age ≥ 18 years, irrespective of gender.
• Confirmed diagnosis of locally advanced unresectable or metastatic solid tumor.
• Expected survival ≥ 12 weeks.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1.
• Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days prior to the first study drug administration.
• Adequate bone marrow and organ function.

Additional Inclusion Criteria for Cohort 1:

• Histologically or cytologically confirmed unresectable locally advanced or metastatic NSCLC.
• Tumor harboring EGFR-sensitive mutations (Ex19del or L858R, with or without other EGFR mutations) confirmed via histology or cytology specimens.
• In the safety run-in phase, NSCLC participants who have received prior standard therapy.
• In the cohort expansion phase, participants without driver gene mutations who have not received prior systemic anti-tumor therapy for unresectable locally advanced or metastatic disease.

Additional Inclusion Criteria for Cohort 2:

• Histologically or cytologically confirmed unresectable locally advanced or metastatic non-squamous NSCLC.
• In the safety run-in phase, participants should have received prior standard therapy.

In the cohort expansion phase:

• Cohort 2A: NSCLC participants without driver gene mutations (including at least EGFR, ALK, and ROS1, with written documentation) who have not received prior systemic anti-tumor therapy for unresectable locally advanced or metastatic disease. Participants who received neoadjuvant/adjuvant therapy are eligible if disease recurrence or progression occurred >6 months after the last neoadjuvant/adjuvant therapy.
• Cohort 2B: NSCLC participants with tumor harboring EGFR-sensitive mutations (Ex19del or L858R, with or without other EGFR mutations) confirmed via histology or cytology specimens, who have experienced disease progression after prior EGFR-TKI therapy.

Additional Inclusion Criteria for Cohort 3

• Histologically or cytologically confirmed unresectable locally advanced or metastatic NSCLC.
• Tumor harboring EGFR-sensitive mutations (Ex19del or L858R, with or without other EGFR mutations) confirmed via histology or cytology specimens.
• In the safety run-in phase, participants should have experienced disease progression after prior EGFR-TKI therapy.
• In the cohort expansion phase, NSCLC participants who have not received prior systemic anti-tumor therapy for unresectable locally advanced or metastatic disease. Participants who received neoadjuvant/adjuvant therapy are eligible if disease recurrence or progression occurred >6 months after the last neoadjuvant/adjuvant therapy.

Exclusion criteria

• Participation in any other interventional clinical study, except for observational (non-interventional) studies or the follow-up period after the end of study treatment in an interventional study.
• Prior treatment with antibody-drug conjugate (ADC) drugs bearing a camptothecin or its derivative (topoisomerase I inhibitor) small-molecule payload.
• Prior to the first dose of study drug: a) Within 4 weeks: Received intravenous chemotherapy, macromolecular targeted therapy, antibody-drug conjugates, immunotherapy, endocrine therapy, cell therapy, intraperitoneal perfusion chemotherapy, tumor embolization, or interventional chemotherapy. b) Within 2 weeks or 5 half-lives (whichever is shorter): Received oral chemotherapy, small-molecule targeted therapy, or traditional Chinese herbal medicines indicated for anti-tumor treatment. c) Within 4 weeks: Received radical radiotherapy; within 2 weeks: Received palliative radiotherapy. d) Within 2 weeks or 5 half-lives (whichever is shorter): Received strong inhibitors or strong inducers of cytochrome P450 3A4 (CYP3A4). e) Within 4 weeks: Underwent major surgery (craniotomy, thoracotomy, laparotomy, or other surgeries deemed ""major"" by the investigator, excluding puncture biopsy), or has severe unhealed wounds, trauma, or ulcers; within 2 weeks: Underwent laparoscopic exploratory surgery. f) Within 4 weeks: Received live vaccine (mRNA and non-replicating adenovirus vaccines are not considered live vaccines).
• Presence of adverse events from prior anti-tumor therapy that have not resolved to Grade 0 or 1 per NCI-CTCAE v5.0 \[excluding Grade 2 alopecia, fatigue, pigmentation, insomnia, peripheral neuropathy, hypomagnesemia, and toxicities stably controlled by medication (e.g., hypothyroidism stably controlled by replacement therapy, hypertension with blood pressure stably controlled below 160/100 mmHg by antihypertensive medication)\].

Additional Exclusion Criteria for Cohort 1:

• History of active autoimmune disease requiring systemic therapy (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic therapy.
• History of significant toxicity associated with immune checkpoint inhibitor administration that required permanent discontinuation of such therapy.

Additional Exclusion Criteria for Cohort 2:

• History of active autoimmune disease requiring systemic therapy (e.g., disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic therapy.
• History of significant toxicity associated with immune checkpoint inhibitor administration that required permanent discontinuation of such therapy.
• History of hemoptysis within 3 months prior to the first dose (blood volume >2.5 mL per cough or cumulative daily hemoptysis >10 mL), or current active bleeding.

Continuous use of aspirin (>325 mg/day) or other non-steroidal anti-inflammatory drugs known to inhibit platelet function within 2 weeks prior to the first dose."

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• SunYat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT07612137 · CIBI3005A102

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗