Brief Title
A Study of RC48-ADC in Patients With HER2-Expressing Locally Advanced or Metastatic Urothelial Carcinoma
Official Title
A Phase 2 Single-Arm, Open-Label, Multi-Center Clinical Study Evaluating the Efficacy and Safety of Disitamab Vedotin for Injection (RC48-ADC) in Patients With HER2-Expressing Locally Advanced or Metastatic Urothelial Carcinoma
Brief Summary
This is a phase 2 single-arm, open-label, multi-center clinical study evaluating the efficacy
and safety of disitamab vedotin for injection (RC48-ADC) in the second-line treatment of HER2
expressing locally advanced or metastatic urothelial carcinoma who have previously received a
platinum-containing chemotherapy regimen.
Detailed Description
This study plans to enroll subjects with HER2-expressing locally advanced or metastatic
urothelial carcinoma who have progressed on or after a platinum-containing regimen.
HER2-expressing is defined as HER2 protein overexpression of primary or metastatic lesions
with an immunohistochemistry (IHC) score of 2+ or 3+.
Upon enrollment, eligible subjects will receive intravenous infusions of RC48 ADC at a dose
of 2.0 mg/kg once every 2 weeks (maximum dose 200 mg). Subjects will keep receiving the drug
until disease progression, intolerable toxicity, subject withdrawal, death, or termination of
the study by the sponsor.
During the study, the evaluation of tumor lesions will be based on Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1. An independent review committee (IRC) is
established to review all tumor evaluation results.
Traditional pharmacokinetic analysis will be conducted via Non-compartmental analysis (NCA)
in a subgroup of approximately 20 subjects to assess the PK profiles of total antibody,
RC48-ADC and free MMAE following single-dose and repeat doses of RC48-ADC.
Sparse pharmacokinetic sampling will be collected in the other subjects for the purpose of
population pharmacokinetic analysis and exposure-response analyses in the overall study
population.
After treatment, each subject will receive a survival follow-up visit every 3 months until
death, loss to follow-up, withdrawal of informed consent, or termination of the study as
decided by the sponsor.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
objective response rate (ORR) based on RECIST version 1.1 assessed by independent radiology review
Secondary Outcome
ORR by Investigator
Condition
Urothelial Carcinoma
Intervention
Disitamab Vedotin for Injection
Study Arms / Comparison Groups
Disitamab Vedotin for Injection (RC48-ADC)
Description: Upon enrollment, eligible subjects will receive intravenous infusions of RC48 ADC at a dose of 2.0 mg/kg once every 2 weeks (maximum dose 200 mg). Subjects will keep receiving the drug until disease progression, intolerable toxicity, subject withdrawal, death, or termination of the study by the sponsor.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
59
Start Date
September 2021
Completion Date
October 2022
Primary Completion Date
January 2022
Eligibility Criteria
Inclusion Criteria:
1. Voluntary participation and informed consent
2. Male or female, ≥ 18 years of age
3. Expected survival ≥ 12 weeks
4. Locally advanced or metastatic but unresectable urothelial carcinoma with
histopathological confirmation (including urothelial carcinoma originating from renal
pelvis, ureters, bladder, or urethra)
5. Subjects diagnosed with unresectable, locally advanced or metastatic disease who
develop disease progression on or after receiving a platinum containing regimen
6. At least one measurable lesion based on RECIST version 1.1 (≥ 20 mm as measured by
conventional CT, ≥ 10 mm as measured by Spiral CT, and have not undergone radiotherapy
for the measurable lesion). Tumor lesions previously treated with radiotherapy are
considered measurable if progression is demonstrated at the time of enrollment
7. HER2-expressing status confirmed by the central laboratory: IHC 2+ or 3+; Subject is
able to provide specimens from primary or metastatic lesions for HER2 tests
8. ECOG performance status score: 0 or 1
9. Adequate cardiac, bone marrow, hepatic and renal functions (based on normal reference
ranges of the clinical trial site):
- Left ventricular ejection fraction (LVEF) ≥ 50%
- QTcF < 470 ms
- Hemoglobin ≥ 9.0 g/dL without transfusion
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelets count ≥ 100 x 109/L
- Total serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Without liver metastasis: ALT and AST ≤ 2.5 x ULN; With liver metastasis: ALT and
AST ≤ 5 x ULN
- Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 50 mL/min as
calculated by the Cockcroft-Gault equation
10. Willingness to avoid pregnancy or fathering children based on the criteria below:
1. Women of non-childbearing potential (i.e., surgically sterile with a hysterectomy
and/or bilateral oophorectomy OR chemically sterile OR ≥ 12 months of amenorrhea
in the absence of chemotherapy, anti-estrogens, or ovarian suppression). Women of
non-childbearing potential need not undergo pregnancy testing
2. Women of childbearing potential who have a negative urine or serum pregnancy test
at Screening and before the first dose of study drug on Cycle 1, Day 1, and who
agree to take appropriate precautions to avoid pregnancy (with approximately 99%
certainty) from Screening through 6 months after the last dose of study drug
3. Men who agree to take appropriate precautions to avoid fathering children (with
at least 99% certainty) from Screening through 6 months after the last dose of
study drug
11. Subject must be willing and able to comply with the trial procedure and the follow-up
schedule.
Exclusion Criteria:
1. Known hypersensitivity to disitamab vedotin for injection or any of its components
2. Received anti-tumor treatment (including chemotherapy, radiotherapy, targeted therapy,
immunotherapy etc.) or participated in another clinical study within 4 weeks prior to
the start of the study, or toxicity from a previous treatment that has not returned to
Grade 0-1 (except for Grade 2 alopecia)
3. Received treatment with other antibody-drug conjugates (such as enfortumab vedotin,
trastuzumab emtansine, etc.)
4. Major surgery that has not fully recovered within 4 weeks prior to dose administration
5. Received live vaccines (except for vaccines for COVID-19 )within 4 weeks prior to dose
administration or plan on receiving any vaccine (except for vaccines for COVID-19 )
during the course of the study
6. Other serious, uncontrolled concomitant diseases that may affect protocol compliance
or interpretation of outcomes, including active opportunistic infections or advanced
(severe) infections, uncontrolled diabetes, cardiovascular diseases (NYHA Class III-IV
heart failure, Grade II or more severe heart block, myocardial infarction, unstable
arrhythmia or unstable angina within the past 12 months, cerebral infarction within
the past 6 months, etc.) or pulmonary diseases (interstitial pneumonia, obstructive
pulmonary disease, or history of symptomatic bronchospasm), and deep vein thrombosis
or pulmonary embolism within the past 6 months
7. History of other malignant tumors within 5 years prior to dose administration, except
for:
- Localized, low-risk prostate cancer (subjects with stage ≤ T2b, Gleason score ≤
7, and prostate-specific antigen (PSA) ≤ 20 ng/mL (if measured) at diagnosis, who
have undergone radical treatment and have no PSA recurrence may participate in
this study);
- Malignancies that can be cured after treatment (including but not limited to
adequately treated thyroid cancer, cervical carcinoma in situ, basal or squamous
cell skin cancer, or radical treatment of ductal carcinoma in situ of the breast)
8. Central nervous system metastasis and/or carcinomatous meningitis. Subjects who have
undergone treatment for brain metastasis may be eligible, provided that: the subject
has been in stable condition for at least 6 months; no radiographic evidence of
disease progression within 4 weeks prior to the first dose; all neurological symptoms
have returned to baseline levels; no new or growth of brain metastasis; and the
subject has discontinued radiation, surgery or steroid therapy at least 28 days prior
to the first dose. This does not include subjects with carcinomatous meningitis, who
are not eligible even if clinically stable
9. Active autoimmune diseases that require systemic therapy (such as the use of
disease-modifying drugs [e.g., methotrexate, sulfasalazine, leflunomide,
hydroxychloroquine], corticosteroids, or immunosuppressives) over the past 2 years.
Replacement therapies (such as thyroxine, insulin, or physiological replacement of
glucocorticoids due to renal or pituitary deficiency) are allowed
10. Received allogeneic hematopoietic stem cell transplantation or solid organ
transplantation
11. Pleural effusion or ascites with symptoms or requiring symptomatic treatment
12. Pregnant or breastfeeding women
13. Positive HIV test, with a lower CD4+ count (<350 cells/μL)
14. Subjects with uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or
diastolic blood pressure >100 mmHg)
15. Subjects with active Hepatitis B and/or Hepatitis C:
- For subjects with positive HBsAg, only those whose HBV DNA < 500 IU/mL are
eligible.
- As for subjects with positive anti-HCV, only those who have a negative HCV RNA
PCR test are eligible
16. Active tuberculosis
17. Any other disease, metabolic disorder, or abnormal finding upon physical examination
or laboratory examination that makes the subject unsuitable for receiving the
investigational drug, affects the interpretation of study outcomes, or poses risks to
subject safety, as determined by the investigator
18. A positive real-time reverse transcriptase polymerase chain reaction (RT-PCR) test for
SARS CoV-2.
19. Clinical signs and symptoms consistent with SARS-CoV-2 infection (e.g., fever, dry
cough, dyspnea, sore throat, fatigue) or positive SARS-CoV-2 test result within 2
weeks prior to screening.
20. Severe course of COVID-19 (e.g., extracorporeal membrane oxygenation, mechanically
ventilated).
21. Subject compliance is questionable
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 1-301-284-1015, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04879329
Organization ID
RC48 G001
Responsible Party
Sponsor
Study Sponsor
RemeGen Co., Ltd.
Study Sponsor
, ,
Verification Date
April 2021