A Study of RC48-ADC(Antibody Drug Conjugate) and JS001 to Evaluate the Safety and Pharmacokinetics of Subjects With Locally Advanced or Metastatic Urothelial Cancer

• ClinicalTrials.gov Identifier: NCT04264936
• Recruitment Status: Unknown
• First Posted: February 11, 2020
• Last Update Posted: February 13, 2020
• Sponsor: Peking University Cancer Hospital & Institute
• Information provided by (Responsible Party): Jun Guo, Peking University Cancer Hospital & Institute

Study Description

Brief Summary:

This is an open-label, single-arm, Phase Ib/II investigator-initiated trial of RC48-ADC combined with JS001 to evaluate the safety and pharmacokinetics of subjects with locally advanced or metastatic urothelial cancer

Condition or disease	Intervention/treatment	Phase
Urothelial Carcinoma	Drug: RC48-ADC and JS001	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Open-label, Single-arm, Phase Ib/II Study of RC48-ADC and JS001 to Evaluate the Safety and Pharmacokinetics of Subjects With Locally Advanced or Metastatic Urothelial Cancer
• Estimated Study Start Date: February 15, 2020
• Estimated Primary Completion Date: January 30, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: RC48-ADC and JS001	Drug: RC48-ADC and JS001; Recombinant Humanized anti-HER2(Human epidermal growth factor receptor-2) Monoclonal Antibody-MMAE(Monomethyl Auristatin E) Conjugate For Injection and JS001 Injection

Outcome Measures

Primary Outcome Measures :

1. Adverse events [ Time Frame: through study completion, an average of 1 year ]
   rate of adverse events
2. maximal tolerated dose [ Time Frame: through study completion, an average of 1 year ]
   dose-limiting toxity

Secondary Outcome Measures :

1. Peak Plasma Concentration(Cmax) [ Time Frame: through study completion, an average of 1 year ]
   Maximum observed plasma concentration
2. Immunogenicity [ Time Frame: through study completion, an average of 1 year ]
   Numbers of participants with anti-drug antibody positive
3. objective response rate [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first；assessed up to 60 months ]
   evaluated by RECIST 1.1 every 8 weeks
4. the area under the curve (AUC) [ Time Frame: through study completion, an average of 1 year ]
   Area under the plasma concentration versus time curve

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Signed informed consent form; Aged 18 years and above; ECOG(Eastern Cooperative Oncology Group) performance is 0 or 1; Life expectancy greater than 12 weeks; Patients with locally advanced or metastatic malignant urothelial carcinoma which is platinum naive and cisplatin ineligible, or progressed after at least one line standard systemic chemotherapy (including progression within 12 months of neo-/adjuvant therapy);

Cisplatinum ineligible patients should meet one of the following criteria:

1. Aged 70 years and above, and ECOG performance is 1;
2. Serum creatinine >= 1.0xULN or CrCl<60ml/min;
3. Lose of hearing >= Grade 2;
4. Peripheral nerve disorder >= Grade 2 Patients with measurable and appreciable tumor lesions according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1); Willing to provide primary lesion samples for the purpose of PD-L1 and HER2 tests.

Adequate organ function as defined by the following criteria:

1. absolute neutrophil count(ANC) >= 1.5 x 10^9/L;
2. platelets>=100* 10^9/L;
3. Total serum creatinine <=1.5*ULN;
4. serum aspartate transaminase (AST) and serum alanine transaminase (ALT) <=2.5*upper limit of normal (ULN), or AST and ALT<=5*ULN if liver function abnormalities are due to underlying malignancy; normal serum creatinine ;
5. Left ventricular ejection fraction (LVEF) >=50%
6. Hemoglobin>=9g/dl Women of child-bearing potential and men must agree to use adequate contraception (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete sexual abstinence, or sterilized partner) prior to study entry and during the period of therapy and for 30 days after the last dose of study drug;

Exclusion Criteria:

• Allergy to RC48-ADC, or JS001, or their components Received anti-cancer therapy including chemotherapy, radiotherapy, immunotherapy or other clinical trial treatments within 3 weeks of starting study treatment Unresolved toxicities from prior anti-cancer therapy, except for alopecia Previously treated with HER2-ADC and/or anti-PD-1 or anti-PD-L1 or anti PD-L2 therapies; Underwent major surgery within 4 weeks of first dose of study drug and not completely recovered; Received vaccine within 4 weeks of first dose of study drug Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, or greater than or equal to Class 2 congestive heart failure as defined by the New York Heart Association Functional Classification, or history of myocardial infarction unstable angina, or acute coronary syndrome within 6 months prior to enrollment in the study; History of other neoplastic disease within 3 years prior to the study drug, with exception of resolved/curable cancers such as basal skin cancer or squamous cell skin cancer,.

Metastasis to CNS(central nervous system) and/or carcinomatous meningitis, with exception for the patients who received treatment of metastasis to CNS and/or carcinomatous meningitis and had stable disease for at least 3 months, and no evidence of progression within 4 weeks of first dose of study treatment. No evidence of new or expanded metastasis, and untreated with radiotherapy, surgery or steroid therapy within 4 weeks of first dose of study treatment.

History of allogeneic hematopoietic stem cell transplantation or organ transplantation; Patients who had received systemic steroid therapy within the last 2 years; Pregnancy or lactation; Positive results of HIV testing; Active HBV(hepatitis B virus) or HCV(hepatitis C virus) infection Active tuberculosis; Other disorders with clinical significance according to the researcher's judgment; Unwilling or unable to participate in all required study evaluations and procedures

Contacts and Locations

Contacts

Contact: xinan sheng, doctor.; 010-88196348; doctor_sheng@126.com

Locations

China, Beijing

Beijing Cancer Hospital; Recruiting

Beijing, Beijing, China, 100142

Contact: Jun Guo, MD 010-88121122 guoj307@126.com

Sponsors and Collaborators

Peking University Cancer Hospital & Institute

More Information

• Responsible Party: Jun Guo, Director, Peking University Cancer Hospital & Institute
• ClinicalTrials.gov Identifier: NCT04264936
• Other Study ID Numbers: RC48-C014
• First Posted: February 11, 2020
• Last Update Posted: February 13, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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