A TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND EFFICACY OF SHR-A1904 IN SUBJECTS WITH ADVANCED SOLID TUMORS

NCT05277168 | Recruiting Phase 1 FDA Drug

• 1 other identifier: SHR-A1904-I-104
• Study Type: interventional
• Target: 83
• Locations: 4 countries
• Sites: 28

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (4)

• Dose-limiting toxicity (DLT)

  DLT is defined during the first cycle of the study treatment and assessed as certainly or at least possibly related to SHR-A1904 treatment.

  the first cycle of administration, up to 21 days

• Maximum tolerated dose (MTD)

  defined as the dose with the estimated toxicity probability which is the closest to the target toxicity probability.

  the first cycle of administration, up to 21 days

• Recommended Phase 2 Dose (RP2D)

  RP2D is the dose selected for further study based on the phase I study results.

  the first cycle of administration, up to 21 days

• Adverse events (AEs) and serious adverse events (SAEs)

  from the signing of informed consent form to the end of safety follow-up period (90 days after the last dose)

Secondary Outcomes (7)

• Objective response rate (ORR)

  evaluated until the end of study, approximately 12 months after the first dose of study drug of the last subject, currently estimated March 2026

• Duration of response (DoR)

  evaluated until the end of study, approximately 12 months after the first dose of study drug of the last subject

• Clinical benefit rate (CBR)

  evaluated until the end of study, approximately 12 months after the first dose of study drug of the last subject

• Progression-free survival (PFS)

  evaluated until the end of study, approximately 12 months after the first dose of study drug of the last subject

• Overall survival (OS)

  until the end of study, approximately 12 months after the first dose of study drug of the last subject

Study Arms (1)

Single Arm

EXPERIMENTAL

Single Arm : SHR-A1904

Drug: SHR-A1904

Interventions

SHR-A1904 DRUG

Single Arm ：It is a dose-escalation and dose-expansion study of SHR-A1904 in subjects with advanced solid tumors

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evidence of a personally signed and dated ICF indicating that the subject has been informed of all pertinent aspects of the study.
• Age \>18.
• ECOG performance status of 0-1.
• Life expectancy of ≥3 months.
• 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.
• 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.
• Has at least one measurable lesion as defined by RECIST v1.1.
• 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%.
• 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).

You may not qualify if:

• Plan to receive any other anti-tumor treatments during the treatment period of this study.
• Subjects participated in a prior investigational study or received anticancer treatment, and have not recovered from side effects of such therapy.
• Underwent major surgical operation within 4 weeks before the first dose of this IP.
• 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.
• Previously received total gastrectomy (only for subjects of the dose-escalation part.
• 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).
• Known to be allergic to any component of SHR-A1904 product (antibody conjugated toxin, antibody), or allergic to humanized monoclonal antibody products.
• 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.
• 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.
• 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.
• 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.
• Serious infections that require use of intravenous antibiotics, antiviral drugs, or antifungal drugs during the study period.
• 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
• Has a history of immunodeficiency (including positive results of HIV test in screening, and other acquired and congenital immunodeficiencies) or organ transplant.
• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (28)

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

ACTIVE NOT RECRUITING

Comprehensive Hematology Oncology

St. Petersburg, Florida, 33709, United States

TERMINATED

LSU Health Sciences Center

New Orleans, Louisiana, 70112, United States

ACTIVE NOT RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

TERMINATED

Rhode Island Hospital

Providence, Rhode Island, 02905, United States

TERMINATED

Prisma Health

Greenville, South Carolina, 29605, United States

ACTIVE NOT RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

Central Coast Local Health District

Gosford, New South Wales, 2250, Australia

COMPLETED

Sydney South West Private Hospital

Liverpool, New South Wales, Australia

RECRUITING

Scientia Clinical Research Ltd

Randwick, New South Wales, 2031, Australia

RECRUITING

Genesis Care North Shore

St Leonards, New South Wales, 2065, Australia

COMPLETED

Macquarie University

Sydney, New South Wales, 2109, Australia

RECRUITING

Westmead Hospital

Westmead, New South Wales, 2145, Australia

RECRUITING

Gold Coast Private Hospital

Southport, Queensland, 4215, Australia

NOT YET RECRUITING

Peninsula and South Eastern Haematology & Oncology Group (PASO)

Frankston, Victoria, 3199, Australia

RECRUITING

One Clinical Research (OCR)

Nedlands, Western Australia, 8000, Australia

RECRUITING

National Institute of Oncology, Arensia Research Clinic

Chisinau, MD-2000, Moldova

ACTIVE NOT RECRUITING

Dong-A University Hospital

Busan, 49201, South Korea

RECRUITING

Chungbuk National University Hospital

Cheongju-si, 28644, South Korea

RECRUITING

Ajou University Hospital

Gyeonggi-do, 16499, South Korea

RECRUITING

Seoul National University Bundang Hospital

Seongnam, KS009, South Korea

RECRUITING

CHA Bundang Medical Centre

Seongnam-si, 13496, South Korea

RECRUITING

Korea University Anam Hospital

Seoul, 02841, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, 02841, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06531, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 3080, South Korea

RECRUITING

Central Study Contacts

Bo Chao

CONTACT

+41 79 47 68 792; bo.chao@hengrui.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: SHR-A1904 in Subjects with Advanced Solid tumors

Study Record Dates

• First Submitted: March 3, 2022
• First Posted: March 14, 2022
• Study Start: May 30, 2022
• Primary Completion: March 3, 2026
• Study Completion (Estimated): May 30, 2026
• Last Updated: January 2, 2026

Record last verified: 2025-12

Locations

KR (11); AU (9); US (7); MO (1)