A Study of IBI363 in Subjects With Advanced Malignancies

Phase Ib Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of IBI363 Combination Therapy in Subjects With Advanced Malignancies

This is an open-label, multicenter Phase Ib study to evaluate the safety, tolerability, and efficacy of IBI363 in advanced malignancies patients

Study Overview

• Status: Recruiting
• Conditions: Advanced Malignancies
• Intervention / Treatment: Drug: IBI363 + chemotherapy; Drug: IBI363 + Investigator's Choice SOC

• Study Type: Interventional
• Enrollment (Estimated): 556
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: binbin Min; Phone Number: 0512-69566088; Email: bingo.min@innoventbio.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 20030
      • Recruiting
      • Shanghai Chest Hospita
      • Principal Investigator: Dingzhi Huang, M.D.
      • Principal Investigator: yuping Sun, M.D.
      • Principal Investigator: jianwei Yang, M.D.
      • Principal Investigator: Guiying Wang, M.D.
      • Principal Investigator: yongchang Zhang, M.D.
      • Contact: shun Lu; Phone Number: 021-22200000; Email: shunlu_shchest@sina.com
      • Principal Investigator: hongxia Lu, M.D.
      • Principal Investigator: yifu He, M.D.
      • Principal Investigator: lifeng Wang, M.D.
      • Principal Investigator: xiaobing Chen, M.D.
      • Principal Investigator: yong Li, M.D.
      • Principal Investigator: zhiwei Li, M.D.
      • Principal Investigator: haibo Zhu, M.D.
      • Principal Investigator: haijun Zhong, M.D.
      • Principal Investigator: zuoxing Niu, M.D.
      • Principal Investigator: Runxiang Yang, M.D.
      • Principal Investigator: qiming Wang, M.D.
      • Principal Investigator: haohui Fang, M.D.
      • Principal Investigator: leilei Yuan, M.D.
      • Principal Investigator: zhentian Liu, M.D.
      • Principal Investigator: yifen Wu, M.D.
      • Principal Investigator: Ruinian Zheng, M.D.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Sign written informed consent and be able to comply with the program's visit schedule and related procedures.
2. Male or female subjects, age 18~75 years.
3. Histologically or cytologically confirmed advanced malignancy.
4. Subjects who have progressed on standard therapy, who are unsuitable for standard therapy, who do not have standard therapy, or who have refused standard therapy. For particular cohort, subjects who have not received prior systemic therapy for advanced disease.
5. At least one measurable lesion (target lesion) per RECIST v1.1.
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
7. Life expectancy of 3 months or more.
8. Female subjects of childbearing age or male subjects whose partners are female subjects of childbearing age agree to strictly adopt effective contraceptive measures throughout the entire treatment period and 6 months after the treatment period.

Exclusion Criteria:

1. Women who are pregnant or lactating, or intending to become pregnant before, during, or within 6 months after the last dose of study drug.
2. Active or untreated CNS metastases confirmed by imaging evaluation during screening or previous imaging evaluation. Patients with asymptomatic brain metastases may participate in this study.
3. History of active thrombosis or deep vein thrombosis or pulmonary embolism within 4 weeks prior to the first dose of study drug.
4. Clinically significant cardiovascular or cerebrovascular disease.
5. Interstitial pneumonia, pulmonary fibrosis, pneumoconiosis, drug-associated pneumonia, and radiation pneumonitis requiring steroid hormone or other therapy, as well as history of severe abnormal lung function or other forms of restrictive lung disease.
6. History of allergies, asthma, atopic dermatitis.
7. Concomitant pleural or pericardial effusion requiring repeated drainage or with significant symptoms.
8. Active autoimmune disease requiring systemic therapy within 2 years prior to first dose.
9. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
10. Subjects with known or suspected hypersensitivity to the study drug and any excipients.
11. Subject has a prior history of significant toxicity associated with immune checkpoint inhibitor administration that requires permanent discontinuation.
12. Subjects with unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy, with the exception of persistent Grade 2 alopecia, peripheral neuropathy, hypomagnesemia, and toxicities that are not expected to be reversible but are stably controlled by medications (e.g., hypothyroidism stably controlled by substitution therapy, hypertension stably controlled by antihypertensive medications with a BP of less than 160/100 mmHg).
13. Inadequate recovery from previous surgery or any major surgery within 4 weeks prior to the first dose of study drug.
14. Active uncontrolled bleeding or known bleeding tendency.
15. Subject has a current or recent (within 6 months) major gastrointestinal disease or condition.
16. Subjects with uncontrolled tumor-related pain or symptomatic hypercalcemia.
17. Known positive HIV test, active hepatitis B, hepatitis C (HCV), tuberculosis.
18. Severe/active/uncontrolled infection, infection requiring systemic intravenous antibiotic therapy, or unexplained fever within 2 weeks prior to the first dose of study drug.
19. Diagnosis of another malignancy within 5 years prior to the first dose, exceptions include radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radically resected carcinoma in situ, as well as post-radical localized prostate cancer, and papillary thyroid cancer.
20. Exclusion of contraindications to combination medications including, but not limited to: known contraindications to irinotecan therapy for the combination irinotecan or liposomal irinotecan cohort including, but not limited to: having the UGTA1*6/*6, UGT1A1*28/*28, or UGT1A1*6/*28 genotypes; history of prior pelvic and abdominal radiotherapy.
21. Presence of any disease, treatment or laboratory test abnormality, or history or current evidence of substance abuse that, in the judgment of the investigator, may compromise the safety of the subject, interfere with obtaining informed consent, affect subject compliance, or compromise the safety evaluation of the study drug.
22. Mental illness, presence of altered mental status, or substance abuse that prevents understanding of the informed consent process and/or completion of necessary study-related evaluations.
23. For known or foreseeable reasons, the Investigator believes that the subject is unable to fulfill the requirements of the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; IBI363 combined with chemotherapy in patients with advanced NSCLC who have failed at least one prior line of standard therapy (which needs to include immunotherapy)	Drug: IBI363 + chemotherapy; In this group, patients will receive IBI363 and chemotherapy
Experimental: Cohort 2A; IBI363 combined with chemotherapy as first-line in patients with advanced colorectal cancer, including a safety run-in phase and a randomized controlled phase	Drug: IBI363 + chemotherapy; In this group, patients will receive IBI363 and chemotherapy
Experimental: Cohort 2B; IBI363 combined with chemotherapy as first-line in patients with advanced colorectal cancer, including a safety run-in phase and a randomized controlled phase	Drug: IBI363 + chemotherapy; In this group, patients will receive IBI363 and chemotherapy
Experimental: Cohort 3; IBI363 combined with chemotherapy in patients with advanced biliary tract tumors that have failed or are intolerant to first-line standard therapy	Drug: IBI363 + chemotherapy; In this group, patients will receive IBI363 and chemotherapy
Experimental: Cohort 4; IBI363 combined with chemotherapy in second-line in patients with Advanced Esophageal Squamous Cell Carcinoma	Drug: IBI363 + chemotherapy; In this group, patients will receive IBI363 and chemotherapy
Experimental: Cohort 5; IBI363 combined with chemotherapy in second-line in patients with Advanced Gastric Cancer	Drug: IBI363 + chemotherapy; In this group, patients will receive IBI363 and chemotherapy
Experimental: Cohort 6; IBI363 combined with chemotherapy in patients with Advanced Triple-Negative Breast Cancer	Drug: IBI363 + chemotherapy; In this group, patients will receive IBI363 and chemotherapy
Experimental: Cohort 7; IBI363 combined with chemotherapy in patients with platinum-resistant ovarian cancer that has failed or is intolerant to standard therapy	Drug: IBI363 + chemotherapy; In this group, patients will receive IBI363 and chemotherapy
Experimental: Cohort 8; IBI363 Combined with Investigator's Choice Standard of Care(SOC) in Patients with Advanced Solid Tumors	Drug: IBI363 + Investigator's Choice SOC; In this group, patients will receive IBI363 and Investigator's Choice SOC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Enent (AE)	Adverse events will be assessed by investigator(s) according to NCI-CTCAE v5.0	Up to 90 days after the last administration
Treatment-Emergent AE (TEAE)	Adverse events will be assessed by investigator(s) according to NCI-CTCAE v5.0	Up to 90 days after the last administration
Adverse Event of Special Interest (AESI)	Adverse events will be assessed by investigator(s) according to NCI-CTCAE v5.0	Up to 90 days after the last administration
Serious Adverse Event (SAE)	Adverse events will be assessed by investigator(s) according to NCI-CTCAE v5.0	Up to 90 days after the last administration
Objective response rate (ORR)	ORR is defined as the proportion of participants with a complete response (CR) or partial response (PR).	Through out the study (up to 2 years)
disease control rate (DCR)	DCR is defined as the proportion of participants with a complete response (CR) or partial response (PR) or stable disease(SD)	Through out the study (up to 2 years)
time to response (TTR)	TTR is defined as the time from the date of first dose of study drug to the date of first documented tumor response (CR/PR)	Through out the study (up to 2 years)
duration of response (DoR)	DoR is defined as the time from the date of first documented tumor response (CR/PR) until PD/death	Through out the study (up to 2 years)
progression-free survival (PFS)	PFS is defined as the time from the date of first dose of study drug to the date of the first documented progression or death due to any cause, whichever occurs first	Through out the study (up to 2 years)
Overall survival (OS)	OS is defined as the time from the date of first dose of study drug until the date of death from any cause.	Through out the study (an average of 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration (Cmax) of IBI363	PK parameters maximum concentration (Cmax) of IBI363	Up to 2 years
Area under the curve (AUC) of IBI363	PK parameters area under the curve (AUC)?of IBI363	Up to 2 years
Half-life (T1/2) of IBI363	PK parameters half-life (t1/2)?of IBI363	Up to 2 years
Clearance (CL) of IBI363	PK parameters clearance rate of IBI363	Up to 2 years
Volume of distribution (V) of IBI363	PK parameters apparent volume of distribution(V)?of IBI363	Up to 2 years
Immunogenicity of IBI363	Incidence of anti-drug (IBI363) antibody	Up to 2 years

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• Investigators: Principal Investigator: jianming Xu, M.D., Chinese PLA General Hospital; Principal Investigator: tingbo Liang, M.D., The First Affiliated Hospital ZJ University; Principal Investigator: xueli Bai, M.D., The First Affiliated Hospital ZJ University; Principal Investigator: shun Lu, M.D., Shanghai Chest Hospita; Principal Investigator: tao Zhang, M.D., Wuhan Union Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: June 18, 2024
• First Posted (Actual): June 21, 2024

Study Record Updates

• Last Update Posted (Actual): July 18, 2024
• Last Update Submitted That Met QC Criteria: July 16, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CIBI363A103

Drug and device information, study documents

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