Clinical trial NCT05277168: A TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND EFFICACY OF SHR-A1904 IN SUBJECTS WITH ADVANCED SOLID TUMORS
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-03-14
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: SHR-A1904 in Subjects with Advanced Solid tumors
Primary purpose: TREATMENT

Brief summary: The study (dose escalation/expansion) is being conducted to assess the safety and tolerability of SHR-A1904 in subjects with advanced solid tumors, and to determine maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D), to assess preliminary efficacy of SHR-A1904, pharmacokinetic (PK) profile and immunogenicity of SHR-A1904 in subjects with advanced solid tumors.


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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: the first cycle of administration, up to 21 days
measure: Maximum tolerated dose (MTD)
timeFrame: the first cycle of administration, up to 21 days
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: the first cycle of administration, up to 21 days
measure: Adverse events (AEs) and serious adverse events (SAEs)
timeFrame: from the signing of informed consent form to the end of safety follow-up period (90 days after the last dose)
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: evaluated until the end of study, approximately 12 months after the first dose of study drug of the last subject, currently estimated March 2026
measure: Duration of response (DoR)
timeFrame: evaluated until the end of study, approximately 12 months after the first dose of study drug of the last subject
measure: Clinical benefit rate (CBR)
timeFrame: evaluated until the end of study, approximately 12 months after the first dose of study drug of the last subject
measure: Progression-free survival (PFS)
timeFrame: evaluated until the end of study, approximately 12 months after the first dose of study drug of the last subject
measure: Overall survival (OS)
timeFrame: until the end of study, approximately 12 months after the first dose of study drug of the last subject
measure: Time to maximum concentration (Tmax)
timeFrame: up to 30 days after the last dose
measure: Maximum concentration (Cmax)
timeFrame: up to 30 days after the last dose
Other outcomes:
Locations:
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Saint Petersburg
country: United States
facility: Comprehensive Hematology Oncology
state: Florida
city: New Orleans
country: United States
facility: LSU Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: LSU-LCMC Cancer Center Louisiana State University (LSU) Health Sciences Center
state: Louisiana
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Gosford
country: Australia
facility: Central Coast Local Health District
state: New South Wales
city: Liverpool
country: Australia
facility: Sydney South West Private Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Scientia Clinical Research Ltd
state: New South Wales
city: St Leonards
country: Australia
facility: Genesis Care North Shore
state: New South Wales
city: Sydney
country: Australia
facility: Macquarie University
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Southport
country: Australia
facility: Gold Coast Private Hospital
state: Queensland
city: Frankston
country: Australia
facility: Peninsula and South Eastern Haematology & Oncology Group (PASO)
state: Victoria
city: Nedlands
country: Australia
facility: One Clinical Research (OCR)
state: Western Australia
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Centre
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Chișinău
country: Moldova, Republic of
facility: National Institute of Oncology, Arensia Research Clinic
Study officials:
References: