Study of IBI3028 in Participants With Locally Advanced, Unresectable, or Metastatic Solid Tumors

A Phase 1, Multi-Center, Open-Label Study Evaluating IBI3028 Treatment in Participants With Locally Advanced, Unresectable, or Metastatic Solid Tumors

This is a phase 1 multi-center, open-label study evaluating IBI3028 Treatment in participants with locally advanced, unresectable, or metastatic solid tumors

Inclusion Criteria

1. Be able to understand and sign written informed consent to participate in this study, including all assessments and procedures specified in this protocol;

2. Male or female participants aged 18 years or older;

3. Have histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumors;

4. Have at least one evaluable lesion (dose escalation) or measurable lesion (dose expansion) as per RECIST v1.1 within 28 days prior to the first dose of IBI3028;

5. ECOG PS（Eastern Cooperative Oncology Group Performance Status）score of 0-1;

6. Anticipated life expectancy of ≥ 12 weeks;

7. Adequate bone marrow and organ function as evidenced by :

   1. Hematological function: ANC(Absolute neutrophil count) ≥ 1.5 × 10 9 /L; platelet count (PLT) ≥ 90 × 10 9 /L; hemoglobin ≥ 9.0 g/dL, and without receiving granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), thrombopoietin (TPO), interleukin-11, or other leukocyte/platelet stimulating growth factors (including red blood cell and platelet transfusions) within at least 7 days before the first dose of the study drug;
   2. Hepatic function: total bilirubin ≤ 1.5 × ULN (Upper Limit of Normal) (≤ 3 × ULN for participants with Gilbert's syndrome); AST(Aspartate Aminotransferase) and ALT (Alanine Aminotransferase)≤ 2.5 × ULN in the absence of liver metastases (≤ 5 × ULN if liver metastases are present); albumin ≥ 2.8 g/dL;
   3. Renal function: creatinine clearance ≥ 30 mL/min (using Cockcroft-Gault formula); urine protein < 2+ or 24-h total urine protein < 1 g;
   4. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%, no clinically significant pericardial effusion as determined by ECHO or MUGA(Multigated Acquisition), and no clinically significant ECG result;
   5. Coagulation function: International normalized ratio (INR) ≤ 1.5; activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (participants receiving anticoagulant therapy with coagulation function within the range above are allowed);
   6. Pulmonary function: With at least the lowest level of pulmonary reserve, defined as Grade ≤ 1 dyspnea and blood oxygen saturation ≥ 95% in non-oxygen breathing state;

8. Participants (both male and female participants) who will be not of childbearing potential or who agree to use at least 1 highly effective method of contraception during the study (from start of screening or within 2 weeks prior to first dose, whichever occurs first, and continue until 7 months for females and 4 months for males after the last dose of study drug).

Exclusion Criteria

1. Participation in any other interventional clinical study other than an observational (non-interventional) study or during the follow-up period of an interventional study;

2. Prior anti-tumor therapy:

   Participants who have received cytotoxic therapy within 3 weeks or 5 half-lives (whichever is shorter) prior to the first administration of study intervention ; Participants who have received PD-1/PD-L1 therapy within 4 weeks prior to the first administration of study drug; Participants who have received treatment with small molecule targeted therapy within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of the study drug; Palliative radiation therapy within 2 weeks or radical radiation therapy within 4 weeks prior to the first dose of study drug; Participants who had received adoptive cell therapy within 8 weeks prior to the first administration of study intervention.

3. Have received live vaccines within 4 weeks or tumor vaccines within 3 months prior to the first administration of the study drug, or plan to receive any live vaccines during the study;

4. Use of strong cytochrome P450 3A4 (CYP3A4) enzyme inhibitors within 2 weeks or 5 half-lives (whichever is shorter) prior to the first dose of study drug;

5. Adverse reactions caused by previous anti-tumor treatments that have not resolved to Grade 0 or 1 or baseline level according to NCI CTCAE v5.0 before the first dose of the study drug (except for alopecia, fatigue, pigmentation, and other conditions with no safety implications per the Investigator's clinical judgement);

6. Known allergies, hypersensitivity, or intolerance to IBI3028 or its excipients (refer to the Investigator's Brochure);

7. Have undergone major surgery (craniotomy, thoracotomy, or laparotomy, and other surgeries according to Investigators' opinion, excluding needle biopsy) within 4 weeks prior to the first dose of the investigational product, or are expected to undergo major surgery during the study, or have severe unhealed wounds, ulcers, etc.;

8. Known symptomatic central nervous system (CNS) metastases. Participants with asymptomatic CNS metastases (ie, no neurologic syndrome and metastases ≤1.5 cm in diameter) or stable disease after treatment as judged by the investigator may be considered if: they have no metastases in the midbrain, pons, cerebellum, meninges, medulla oblongata, or spinal cord; stable status for at least 4 weeks prior to the first dose of study drug (≤1.5 mg/day dexamethasone or equivalent and baseline anticonvulsants are allowed), and have no new or enlarging CNS metastases as clearly demonstrated by clinical evidence; Note : CNS lesions are not considered target lesions.

9. Uncontrolled disease or condition, including:

   1. Uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals prior to the first dose of the study drug;
   2. With known human immunodeficiency virus (HIV) infection, or HIV positive (HIV 1/2 Ab positive), for participants outside mainland China, participants with positive HIV antibody test at screening are eligible to participate in the study under the premise of undetectable viral load, or well-controlled under antiretroviral therapy (defined as CD4+ T cell count ≥ 350 cells/μL and no history of AIDS-defining opportunistic infection within 12 months before the first dose);
   3. Acute or chronic active hepatitis B (HBsAg positive and/or HBcAb positive, and HBV DNA titer ≥ 10 4 copies/mL or ≥ 2000 IU/mL) or hepatitis C (HCV Ab positive, and HCV RNA > 10 3 copies/mL or above the lower limit of detection);
   4. Active tuberculosis infection, or still receiving anti-tuberculosis treatment, or receiving anti-tuberculosis treatment within 1 year before the first dose of the study drug;
   5. Uncontrolled myocarditis or symptomatic congestive heart failure Class II-IV (New York Heart Association ,NYHA), symptomatic or uncontrolled arrhythmia, QTc interval > 480 ms, or personal or family history of congenital long/short QT syndrome;
   6. Uncontrolled hypertension with SBP ≥ 160 mmHg or DBP ≥ 100 mmHg measured on 2 follow-up visits despite adequate standard treatment;
   7. Current gastrointestinal tract (muscle-derived tube from the oral cavity to the anus, including oral cavity, pharynx, esophagus, stomach, duodenum, jejunum, ileum, cecum, appendix, colon, rectum, and anus) or endotracheal stent implantation;
   8. Significant malnutrition, such as malnutrition requiring parenteral nutrition;
   9. Spinal cord compression that has not been radically cured by surgery and/or radiotherapy;
   10. Ascites, pleural effusion, or pericardial effusion that is symptomatic and requires intervention prior to the first dose of study intervention (participants who do not require treatment or who recover steadily without intervention are eligible).

10. With a history of pneumonia requiring corticosteroid treatment, or a history of clinically significant lung diseases (such as interstitial lung disease, non-infectious pneumonitis, or uncontrolled lung diseases such as pulmonary fibrosis, severe radiation pneumonitis, and acute lung injury), or suspected of having these diseases by imaging during the screening period;

11. Any history of arterial thromboembolic events within 6 months prior to the first dose of the study drug, including myocardial infarction, unstable angina, cerebrovascular stroke, or transient ischemic attack;

12. Esophageal or gastric varices requiring immediate intervention (e.g., ligature or sclerotherapy) or at high risk of bleeding according to the opinion of the investigator or a gastroenterologist or hepatologist. Participants with evidence of portal hypertension (including imaging findings of hypersplenism) or a history of esophageal and gastric variceal bleeding must undergo endoscopic evaluation within 3 months prior to the first dose of the study drug;

13. Any history of life-threatening hemorrhage or hemorrhage requiring blood transfusion, endoscopy, or surgery within 3 months prior to the first dose of the investigational product ;

14. Unhealed gastrointestinal obstruction, perforation, or fistula. At risk of gastrointestinal obstruction or perforation (including but not limited to: acute diverticulitis, abdominal abscess, etc.), history of extensive bowel resection (segmental colectomy or extensive bowel resection accompanied with chronic diarrhea), active inflammatory bowel disease, or Grade ≥ 2 chronic diarrhea;

15. History of immunodeficiency diseases, including congenital or acquired immunodeficiency diseases;

16. History of allogeneic organ transplantation or allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation within 3 months prior to the first dose of the investigational drug, except for corneal transplantation;

17. History of other malignancy within 2 years before the first dose of study drug(s), with the following exceptions:

    1. Malignancy (other than in situ) treated with curative therapy with no known active disease present for ≥ 2 years prior to the first dose of study drug and at low risk of recurrence according to the physician's opinion;
    2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of residual or recurrent disease;
    3. Adequately treated carcinoma in situ without evidence of residual or recurrent disease;
    4. Prostate intraepithelial neoplasia without evidence of prostate cancer;
    5. Adequately treated urothelial papillary non-invasive carcinoma.

18. Presence of any indwelling tubes or drains (such as percutaneous nephrostomy tubes, indwelling Foley catheters, biliary drainage tubes, or peritoneal/pericardial catheters); Note: Thoracic catheters or dedicated central venous access catheters such as Port-A-Cath or Hickman catheters are allowed.

19. Other acute or chronic diseases or laboratory abnormalities, which may increase the risk of participating in the study or receiving the investigational product, interfere with the interpretation of study results, and make the participant unsuitable for participating in the study based on the investigator's judgment;

20. Neurological, mental, or social conditions that affect the compliance with trial requirements, significantly increase the risk of AEs, or affect the participants' signing of written informed consent (IC);

21. Females who are pregnant, have a positive pregnancy test result, or are breastfeeding;

22. Not fit to participate in this study at the discretion of the Investigator.