Evaluating SHR-A1904 for advanced solid tumors

AN OPEN-LABEL, SINGLE-ARM, MULTI-CENTER PHASE I/IIA CLINICAL STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND EFFICACY OF SHR-A1904 IN SUBJECTS WITH ADVANCED SOLID TUMORS

This study is testing a new treatment called SHR-A1904 to see if it is safe and effective for people with advanced solid tumors who have few other options.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 83 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu HengRui Medicine Co., Ltd. (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 28 sites (Miami Beach, Florida and 27 other locations)
• Trial ID: NCT05277168 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety, tolerability, pharmacokinetics, and efficacy of SHR-A1904 in patients with advanced solid tumors. It involves a dose escalation and expansion approach to determine the maximum tolerated dose and recommended phase II dose. Participants will be monitored for preliminary efficacy and immunogenicity of the treatment. The study focuses on patients with specific types of advanced tumors who have limited treatment options.

Who should consider this trial

Good fit: Ideal candidates include adults over 18 with advanced relapsed or refractory solid tumors that express Claudin 18.2 and have limited treatment options.

Not a fit: Patients with solid tumors that do not express Claudin 18.2 or those who are not intolerable to standard of care treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors who have exhausted other treatments.

How similar studies have performed: Other studies targeting Claudin 18.2 have shown promise, indicating potential for success with this approach.

Eligibility criteria

Inclusion Criteria:

1. Evidence of a personally signed and dated ICF indicating that the subject has been informed of all pertinent aspects of the study.
2. Age \>18.
3. ECOG performance status of 0-1.
4. Life expectancy of ≥3 months.
5. Subjects with pathologically diagnosed advanced relapsed or refractory solid tumors, either gastric and gastroesophageal junction (GEJ) cancer, or pancreatic cancer, who are intolerable to SoC, have progressed through all available treatment options, or for whom there is no efficacious treatment available. Subjects must have pathological classification (e.g., adenocarcinoma etc.) documented.
6. Positive expression of Claudin 18.2 (\>=50% of cells with 2+ or 3+ expression, either from fresh or archival tissue) is required prior to enrollment and participation in this study. Positivity for Claudin 18.2 is defined as tumor cells showing partial or complete membrane staining. The percentage of tumor cells at four different staining intensities will be estimated: 0 (no staining), 1+ (weak), 2+ (moderate), and 3+ (strong). The sum of all 4 percentages should equal 100%. The H-score is determined according to the H-Score formula: \[1 x Percentage of tumor cells stained at 1+\] + \[2 x Percentage of tumor cells stained at 2+\] + \[3 x Percentage of tumor cells stained at 3+\] = H-Score (range 0 or 1-300). Actual figure of Claudin 18.2 expression tested by IHC should be documented. Subjects must have pathological classification (e.g., adenocarcinoma) documented.
7. Has at least one measurable lesion as defined by RECIST v1.1.
8. Has adequate organ and bone marrow function within 7 days prior to administration of study treatment defined below: with no blood transfusion or hematopoietic growth factor support within 2 weeks prior to screening): • Absolute neutrophil count (ANC) ≥1.5 × 109 /L • Platelet count (PLT) ≥100 × 109 /L • Hemoglobin (Hb) ≥90 g/L • TBIL ≤1.5 × ULN • ALT and AST ≤3 × ULN (≤5 × ULN for liver metastasis) • Creatinine clearance ≥60 mL/min/1.73 m2 based on Cockcroft-Gault equation (Appendix 5) • Activated partial thromboplastin time (APTT) and prothrombin time (PT) ≤1.5 × ULN. • Fridericia-corrected QT interval (QTcF) ≤450 msec. If ECG demonstrates QTc \>450 msec at screening, an ECG re-examination is allowed, and subjects will be eligible if it demonstrates QTc ≤ 450 msec. • LVEF ≥50%.
9. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 3 days before the first dose. WOCBP and male subjects whose partners are WOCBP must agree to use effective contraception method during the study period and within 5 half-lives of SHR-A1904 + 6 months after the last dose of SHR-A1904. (see Appendix 2 for details).

Exclusion Criteria:

1. Plan to receive any other anti-tumor treatments during the treatment period of this study.
2. Subjects participated in a prior investigational study or received anticancer treatment, and have not recovered from side effects of such therapy.
3. Underwent major surgical operation within 4 weeks before the first dose of this IP.
4. Received treatments with strong CYP3A4, CYP2D6, P-gp, or BCRP inhibitors or inducers within \< 5 half-lives of the drug before the first dose of the study.
5. Previously received total gastrectomy (only for subjects of the dose-escalation part.
6. Adverse events caused by previous anti-tumor treatments have not recovered to Grade ≤1 according to NCI-CTCAE 5.0 (except for alopecia; some tolerable chronic Grade 2 toxicities may also be excluded as judged by the investigator after consultation with the sponsor).
7. Known to be allergic to any component of SHR-A1904 product (antibody conjugated toxin, antibody), or allergic to humanized monoclonal antibody products.
8. Subjects with known brain metastases, unless the participant is \> 1 month from definitive therapy (surgery or radiotherapy), has no evidence of tumor growth on an imaging study and is clinically stable with respect to the tumor at the start of study intervention.
9. Subjects with a second primary cancer, except adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, and other solid tumors curatively treated with no evidence of disease for ≥3 years prior to the first dose of the study.
10. Class III-IV cardiac insufficiency as per the New York Heart Association (NYHA) criteria; arrhythmia requiring long-term drug control; unstable angina or acute myocardial infarction within 6 months before the first dose of the study.
11. Subjects with a history of clinically significant lung diseases (e.g., interstitial pneumonia, radiation pneumonia, and pulmonary fibrosis) or who are suspected to have these diseases by chest imaging at screening period.
12. Serious infections that require use of intravenous antibiotics, antiviral drugs, or antifungal drugs during the study period.
13. Hepatitis B (HBV, chronic or acute; defined as having a known positive hepatitis B surface antigen \[HbsAg\] test at the time of screening) or hepatitis C (HCV) infection requiring treatment
14. Has a history of immunodeficiency (including positive results of HIV test in screening, and other acquired and congenital immunodeficiencies) or organ transplant.
15. Presence of accompanying diseases (such as poorly controlled hypertension, serious diabetes mellitus, thyroid disorder, psychosis, etc.) that may pose serious risks to the safety of the subject or may affect the subject's ability to complete the study, or any other situation as judged by the investigator.

Where this trial is running

Miami Beach, Florida and 27 other locations

• Mount Sinai Comprehensive Cancer Center — Miami Beach, Florida, United States (Active_not_recruiting)
• Comprehensive Hematology Oncology — St. Petersburg, Florida, United States (Terminated)
• LSU Health Sciences Center — New Orleans, Louisiana, United States (Active_not_recruiting)
• University Hospitals Cleveland Medical Center — Cleveland, Ohio, United States (Terminated)
• Rhode Island Hospital — Providence, Rhode Island, United States (Terminated)
• Prisma Health — Greenville, South Carolina, United States (Active_not_recruiting)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Active_not_recruiting)
• Central Coast Local Health District — Gosford, New South Wales, Australia (Completed)
• Sydney South West Private Hospital — Liverpool, New South Wales, Australia (Recruiting)
• Scientia Clinical Research Ltd — Randwick, New South Wales, Australia (Recruiting)
• Genesis Care North Shore — St Leonards, New South Wales, Australia (Completed)
• Macquarie University — Sydney, New South Wales, Australia (Recruiting)
• Westmead Hospital — Westmead, New South Wales, Australia (Recruiting)
• Gold Coast Private Hospital — Southport, Queensland, Australia (Not_yet_recruiting)
• Peninsula and South Eastern Haematology & Oncology Group (PASO) — Frankston, Victoria, Australia (Recruiting)
• One Clinical Research (OCR) — Nedlands, Western Australia, Australia (Recruiting)
• National Institute of Oncology, Arensia Research Clinic — Chisinau, Moldova (Active_not_recruiting)
• Dong-A University Hospital — Busan, South Korea (Recruiting)
• Chungbuk National University Hospital — Cheongju-si, South Korea (Recruiting)
• Ajou University Hospital — Gyeonggi-do, South Korea (Recruiting)
• Seoul National University Bundang Hospital — Seongnam, South Korea (Recruiting)
• CHA Bundang Medical Centre — Seongnam-si, South Korea (Recruiting)
• Korea University Anam Hospital — Seoul, South Korea (Recruiting)
• Korea University Guro Hospital — Seoul, South Korea (Recruiting)
• Severance Hospital, Yonsei University Health System — Seoul, South Korea (Recruiting)
• Asan Medical Center — Seoul, South Korea (Recruiting)
• Samsung Medical Center — Seoul, South Korea (Recruiting)
• Seoul National University Hospital — Seoul, South Korea (Recruiting)

Study contacts

• Study coordinator: Bo Chao

Conditions Advanced Solid Tumors