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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: IBI3005; Drug: Sintilimab; Drug: Bevacizumab biosimilar; Drug: Carboplatin; Drug: Limertinib; Drug: Osimertinib

• Study Type: Interventional
• Enrollment (Estimated): 282
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yang Luo; Phone Number: +86 21 3183 7200; Email: yang.luo@innoventbio.com
• Study Contact Backup: Name: Yulong Zhang; Phone Number: +86 21 3183 7200; Email: yulong.zhang@innoventbio.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • SunYat-sen University Cancer Center
      • Contact: Li Zhang; Phone Number: 020-87343458; Email: zhangli@sysucc.org.cn
      • Contact: Wenfeng Fang; Phone Number: 020-87343458; Email: fangwenfeng@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Exclusion Criteria for Cohort 1:

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.
2. History of significant toxicity associated with immune checkpoint inhibitor administration that required permanent discontinuation of such therapy.

Additional Exclusion Criteria for Cohort 2:

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.
2. History of significant toxicity associated with immune checkpoint inhibitor administration that required permanent discontinuation of such therapy.
3. 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."

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1：IBI3005+Sintilimab+ Carboplatin+IBI305	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: Carboplatin; Second-generation platinum-based chemotherapy drugs
Experimental: Cohort 2：IBI3005+Sintilimab+ Carboplatin	Drug: IBI3005; Bispecific Monoclonal Antibody-Camptothecin Derivative Conjugate for Injection (R & D code: IBI3005); Drug: Sintilimab; Anti-PD-1 Monoclonal Antibody; Drug: Carboplatin; Second-generation platinum-based chemotherapy drugs
Experimental: Cohort 3：IBI3005+Limertinib/Osimertinib	Drug: IBI3005; Bispecific Monoclonal Antibody-Camptothecin Derivative Conjugate for Injection (R & D code: IBI3005); Drug: Limertinib; Third-generation EGFR-TKI; Drug: Osimertinib; Third-generation EGFR-TKI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS)		Up to 3 years
Number of subjects with clinically significant changes in physical examination results	Clinically significant abnormal physical examination findings reported by the investigator.	Up to 3 years
Number of subjects with clinically significant changes in vital signs	Vital signs including body temperature, pulse, respiratory rate, SpO2 and blood pressure	Up to 3 years
progression free survival (PFS)	as evaluated per the RECIST v1.1 criteria.	Up to 3 years
Number of subjects with adverse events	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	Up to 3 years
Number of subjects with treatment emergent adverse events	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	Up to 3 weeks
Number of subjects with adverse events of special interest	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	Up to 3 years
Number of subjects with serious adverse events	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	Up to 3 years
Dose limiting toxicities (DLTs)	Dose limiting toxicities (DLTs) to establish MTD and/or RP2D.	Up to 3 weeks
Number of subjects with clinically significant changes in laboratory tests results	Clinically significant abnormal laboratory tests results reported by the investigator.	Up to 3 years
Objective Response Rate, (ORR）	as evaluated per the RECIST v1.1 criteria.	Up to 3 years
duration of response (DCR)	as evaluated per the RECIST v1.1 criteria.	Up to 3 years
time to response (TTR)	as evaluated per the RECIST v1.1 criteria.	Up to 3 years
duration of response (DoR)	as evaluated per the RECIST v1.1 criteria.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
anti-drug antibody (ADA)	Incidence and characterization of anti-drug antibody (ADA).	Up to 3 years
area under the curve (AUC)	area under the curve (AUC) of single and multiple doses of IBI3005	Up to 3 years
maximum concentration (Cmax)	maximum concentration (Cmax) of single and multiple doses of IBI3005	Up to 3 years
time to maximum concentration (Tmax)	time to maximum concentration (Tmax) of single and multiple doses of IBI3005	Up to 3 years
clearance (CL)	clearance (CL) of single and multiple doses of IBI3005	Up to 3 years
apparent volume of distribution (V)	apparent volume of distribution (V) of single and multiple doses of IBI3005	Up to 3 years
half-life (t1/2)	half-life (t1/2) of IBI3005 to the last administration of IBI3005	Up to 3 years

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: May 21, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Coordination Complexes; Carboplatin; osimertinib; sintilimab
• Other Study ID Numbers: CIBI3005A102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No