Clinical trial NCT06468098: A Study of IBI363 in Subjects With Advanced Malignancies
Official title: Phase Ib Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of IBI363 Combination Therapy in Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Malignancies
Lead sponsor: Innovent Biologics (Suzhou) Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2024-06-21
Enrollment: 556
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Adverse Enent (AE)
timeFrame: Up to 90 days after the last administration
measure: Treatment-Emergent AE (TEAE)
timeFrame: Up to 90 days after the last administration
measure: Adverse Event of Special Interest (AESI)
timeFrame: Up to 90 days after the last administration
measure: Serious Adverse Event (SAE)
timeFrame: Up to 90 days after the last administration
measure: Objective response rate (ORR)
timeFrame: Through out the study (up to 2 years)
measure: disease control rate (DCR)
timeFrame: Through out the study (up to 2 years)
measure: time to response (TTR)
timeFrame: Through out the study (up to 2 years)
measure: duration of response (DoR)
timeFrame: Through out the study (up to 2 years)
measure: progression-free survival (PFS)
timeFrame: Through out the study (up to 2 years)
measure: Overall survival (OS)
timeFrame: Through out the study (an average of 2 years)
Secondary outcomes:
measure: Plasma concentration (Cmax) of IBI363
timeFrame: Up to 2 years
measure: Area under the curve (AUC) of IBI363
timeFrame: Up to 2 years
measure: Half-life (T1/2) of IBI363
timeFrame: Up to 2 years
measure: Clearance (CL) of IBI363
timeFrame: Up to 2 years
measure: Volume of distribution (V) of IBI363
timeFrame: Up to 2 years
measure: Immunogenicity of IBI363
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Chest Hospita
state: Shanghai
Study officials:
affiliation: The First Affiliated Hospital ZJ University
name: tingbo Liang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital ZJ University
name: xueli Bai, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese PLA General Hospital
name: jianming Xu, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Chest Hospita
name: shun Lu, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Wuhan Union Hospital, China
name: tao Zhang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: