Clinical trial NCT03809013: A Open-label, Single-arm, Multicenter, Phase II Study of RC48-ADC to Evaluate the Efficacy and Safety of Subjects With HER2 Overexpressing Locally Advanced or Metastatic Urothelial Cancer
Official title: A Open-label, Single-arm, Multicenter, Phase II Study of RC48-ADC to Evaluate the Efficacy and Safety of Subjects With HER2 Overexpressing Locally Advanced or Metastatic Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urothelial Carcinoma
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-01-18
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of intravenous RC48-ADC in patients with HER2 overexpressing locally advanced or metastatic urothelial cancer.


Eligibility criteria: Inclusion Criteria:

* Voluntary agreement to provide written informed consent.
* Male or female, Age ≥ 18 years.
* Predicted survival ≥ 12 weeks.
* Diagnosed with histologically or cytologically-confirmed locally advanced or metastatic urothelial cancer, originate from bladder, renal pelvis, ureter and urinary tract.
* Unresectable or disease progression (i.e. locally advanced/metastasis) after surgery and at least regular chemotherapy including gemcitabine,cisplatin AND paclitaxel. Disease progression within 6 months of the completion of neo-adjuvant and adjuvant chemotherapy with gemcitabine, cisplatin AND paclitaxel is also eligible.
* Measurable lesion according to RECIST 1.1.
* HER2 overexpressing (i.e. IHC 2+ or 3+) as confirmed by the central lab. Primary or metastatic tumor sample will be provided for HER2 test.
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
* Adequate organ function, evidenced by the following laboratory results within 7 days prior to the study treatment:

Cardiac ejection fraction ≥ 50 %. Hemoglobin ≥ 9g/dL; Absolute neutrophil count ≥ 1.5×109 /L Platelets ≥ 100×109 /L; Total bilirubin ≤ 1.5× ULN; AST and ALT ≤ 2.5×ULN and ≤ 5 × ULN with hepatic metastasis; Serum creatinine ≤1.5×ULN.

* All female subjects will be considered to be of child-bearing potential unless they are postmenopausal, or have been sterilized surgically.Female subjects of child-bearing potential must agree to use two forms of highly effective contraception. Male subjects and their female partner who are of child-bearing potential must agree to use two forms of highly effective contraception.
* Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

* Known hypersensitivity to the components of Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate.
* Toxicity of previous anti-tumor treatment not recovered to CTCAE Grade 0-1 (with exception of Grade 2 alopecia).
* Pleural or abdominal effusion with clinical symptoms that requires ongoing treatment.
* History of major surgery within 4 weeks of planned start of trial treatment.
* Has received a live virus vaccine within 4 weeks of planned start of trial treatment.
* Currently known active infection with HIV or tuberculosis.
* Diagnosed with HBsAg, HBcAb positive and HBV DNA copy positive, or HCVAb positive.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
* History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
* known central nervous system metastases.
* Uncontrolled hypertension, diabetes, Interstitial lung Disease, or COPD;
* Treated with systemic treatment (e.g. immunomodulators, corticosteroids or immunosuppressants) for the autoimmune disease within 2 years prior to the study treatment.
* NYHA Class III heart failure.
* Pregnancy or lactation.
* Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Primary outcomes:
measure: Objective Response Rate （ORR）as assessed by the Independent Review Committee
timeFrame: 24 months
Secondary outcomes:
measure: Objective Response Rate（ORR）as assessed by investigator
timeFrame: 24 months
measure: Progression Free Survival (PFS)
timeFrame: 24 months
measure: Duration of Objective Response (DOR)
timeFrame: 24 months
measure: Disease control rate (DCR)
timeFrame: 24 months
measure: Overall survival (OS)
timeFrame: 24 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Cancer Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Chendu
country: China
facility: West China Hospital
state: Sichuan
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jun Guo, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: