Solid Tumor
Conditions
Brief summary
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
DRUGIBI3005
Bispecific Monoclonal Antibody-Camptothecin Derivative Conjugate for Injection (R \& D code: IBI3005)
DRUGSintilimab
Anti-PD-1 Monoclonal Antibody
Recombinant humanized anti-VEGF monoclonal antibody
DRUGLimertinib
Third-generation EGFR-TKI
DRUGOsimertinib
Third-generation EGFR-TKI
DRUGCarboplatin
Second-generation platinum-based chemotherapy drugs
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has signed a written informed consent form (ICF) and is able to comply with the scheduled study visits and related procedures. 2. Age ≥ 18 years, irrespective of gender. 3. Confirmed diagnosis of locally advanced unresectable or metastatic solid tumor. 4. Expected survival ≥ 12 weeks. 5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1. 6. Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days prior to the first study drug administration. 7. Adequate bone marrow and organ function. Additional Inclusion Criteria for Cohort 1: 1. Histologically or cytologically confirmed unresectable locally advanced or metastatic NSCLC. 2. Tumor harboring EGFR-sensitive mutations (Ex19del or L858R, with or without other EGFR mutations) confirmed via histology or cytology specimens. 3. In the safety run-in phase, NSCLC participants who have received prior standard therapy. 4. 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: 1. Histologically or cytologically confirmed unresectable locally advanced or metastatic non-squamous NSCLC. 2. In the safety run-in phase, participants should have received prior standard therapy. In the cohort expansion phase: 3. 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. 4. 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 1. Histologically or cytologically confirmed unresectable locally advanced or metastatic NSCLC. 2. Tumor harboring EGFR-sensitive mutations (Ex19del or L858R, with or without other EGFR mutations) confirmed via histology or cytology specimens. 3. In the safety run-in phase, participants should have experienced disease progression after prior EGFR-TKI therapy. 4. 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
1. 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. 2. Prior treatment with antibody-drug conjugate (ADC) drugs bearing a camptothecin or its derivative (topoisomerase I inhibitor) small-molecule payload. 3. 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). 4. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with adverse events | Up to 3 years | defined as any untoward medical occurrence, whether or not thereis a causal relationship with the study drug, in a clinical study subject from the time informed consent form is signed |
| Number of subjects with treatment emergent adverse events | Up to 3 weeks | defined as any untoward medical occurrence, whether or not thereis a causal relationship with the study drug, in a clinical study subject from the time informed consent form is signed |
| Number of subjects with adverse events of special interest | Up to 3 years | defined as any untoward medical occurrence, whether or not thereis a causal relationship with the study drug, in a clinical study subject from the time informed consent form is signed |
| Number of subjects with serious adverse events | Up to 3 years | defined as any untoward medical occurrence, whether or not thereis a causal relationship with the study drug, in a clinical study subject from the time informed consent form is signed |
| Dose limiting toxicities (DLTs) | Up to 3 weeks | Dose limiting toxicities (DLTs) to establish MTD and/or RP2D. |
| Number of subjects with clinically significant changes in laboratory tests results | Up to 3 years | Clinically significant abnormal laboratory tests results reported by the investigator. |
| Number of subjects with clinically significant changes in physical examination results | Up to 3 years | Clinically significant abnormal physical examination findings reported by the investigator. |
| Number of subjects with clinically significant changes in vital signs | Up to 3 years | Vital signs including body temperature, pulse, respiratory rate, SpO2 and blood pressure |
| Objective Response Rate, (ORR） | Up to 3 years | as evaluated per the RECIST v1.1 criteria. |
| duration of response (DCR) | Up to 3 years | as evaluated per the RECIST v1.1 criteria. |
| time to response (TTR) | Up to 3 years | as evaluated per the RECIST v1.1 criteria. |
| duration of response (DoR) | Up to 3 years | as evaluated per the RECIST v1.1 criteria. |
| progression free survival (PFS) | Up to 3 years | as evaluated per the RECIST v1.1 criteria. |
| overall survival (OS) | Up to 3 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| area under the curve (AUC) | Up to 3 years | area under the curve (AUC) of single and multiple doses of IBI3005 |
| maximum concentration (Cmax) | Up to 3 years | maximum concentration (Cmax) of single and multiple doses of IBI3005 |
| time to maximum concentration (Tmax) | Up to 3 years | time to maximum concentration (Tmax) of single and multiple doses of IBI3005 |
| clearance (CL) | Up to 3 years | clearance (CL) of single and multiple doses of IBI3005 |
| apparent volume of distribution (V) | Up to 3 years | apparent volume of distribution (V) of single and multiple doses of IBI3005 |
| half-life (t1/2) | Up to 3 years | half-life (t1/2) of IBI3005 to the last administration of IBI3005 |
| anti-drug antibody (ADA) | Up to 3 years | Incidence and characterization of anti-drug antibody (ADA). |
Countries
China
Contacts
CONTACTYang Luo
CONTACTYulong Zhang
Outcome results
None listed