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

NCT03809013 | Completed Phase 2

• 1 other identifier: RC48-C009
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 8

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.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate （ORR）as assessed by the Independent Review Committee

  Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR)

  24 months

Secondary Outcomes (5)

• Objective Response Rate（ORR）as assessed by investigator

  24 months

• Progression Free Survival (PFS)

  24 months

• Duration of Objective Response (DOR)

  24 months

• Disease control rate (DCR)

  24 months

• Overall survival (OS)

  24 months

Study Arms (1)

RC48-ADC

EXPERIMENTAL

Participants will be treated with RC48-ADC 2.0 mg/kg, once every 2 weeks (Q2W) until investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or participant's decision to withdraw from therapy, or death (whichever occurs first).

Drug: RC48-ADC

Interventions

RC48-ADC DRUG

2.0mg/kg IV every 2 weeks

Also known as: Recombinant Humanized anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection

RC48-ADC

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• RemeGen Co., Ltd.: lead

Study Sites (8)

Anhui Cancer Hospital

Hefei, Anhui, China

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100078, China

Location

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Location

Peking University First Hospital

Beijing, Beijing Municipality, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Location

Hunan Cancer Hospital

Changsha, Hunan, China

Location

Qilu Hospital of Shandong University

Jinan, Shandong, China

Location

West China Hospital

Chengdu, Sichuan, China

Location

Related Publications (1)

• Sheng X, Wang L, He Z, Shi Y, Luo H, Han W, Yao X, Shi B, Liu J, Hu C, Liu Z, Guo H, Yu G, Ji Z, Ying J, Ling Y, Yu S, Hu Y, Guo J, Fang J, Zhou A, Guo J. Efficacy and Safety of Disitamab Vedotin in Patients With Human Epidermal Growth Factor Receptor 2-Positive Locally Advanced or Metastatic Urothelial Carcinoma: A Combined Analysis of Two Phase II Clinical Trials. J Clin Oncol. 2024 Apr 20;42(12):1391-1402. doi: 10.1200/JCO.22.02912. Epub 2023 Nov 21.

  PMID: 37988648 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

Injections

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Jun Guo, Ph.D

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2019
• First Posted: January 18, 2019
• Study Start: January 7, 2019
• Primary Completion: March 4, 2021
• Study Completion: June 5, 2023
• Last Updated: November 27, 2023

Record last verified: 2023-11

Locations

CN (8)