Clinical trial NCT02738489: A Study to Evaluate the Safety and Tolerability of Using the SHR-1210 in Patients With Advanced Melanoma
Official title: An Open-Label, Single Center, Nonrandomized, Dose-Escalation Phase 1 Study to Evaluate Safety and Tolerability of SHR-1210 in Subjects With Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Melanoma
Keywords: PD-1/PD-L1 Advanced Melanoma Immunotherapy
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2016-04-14
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, single center, non-randomized, dose escalation phase I trial to evaluate safety and tolerability of SHR-1210 (camrelizumab) in patients with advanced melanoma with disease progression after standard treatment, unresectable lesions, or metastases. Between Apr 13, 2016, and Jan 8, 2020, 36 patients were enrolled from Beijing Cancer Hospital.


Eligibility criteria: Inclusion Criteria:

1. Male or female patients aged 18-70 years old, who agree to provide pathological tumor biopsy specimens during the screening period and after the end of treatment.
2. Patients with pathologically confirmed advanced melanoma who have failed standard treatments or without effective treatment methods (e.g., chemotherapy, targeted therapy and immunotherapy other than those targeting PD-1/PD-L1).
3. ECOG PS: 0-1.
4. Life expectancy ≥ 12 weeks.
5. With measurable and evaluable lesion(s) according to RECIST v1.1.

Exclusion Criteria:

1. Patients with active autoimmune diseases or a history of autoimmune diseases (including but not limited to the following: interstitial pneumonitis, uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, hypothyroidism; adults with vitiligo or completely relieved childhood asthma can be enrolled if they do not require any intervention; patients with asthma requiring medical intervention with bronchodilators cannot be enrolled).
2. Patients who are currently using immunosuppressive agents, or systemic or absorbable local hormonal therapies for immunosuppression purposes (\> 10 mg/day prednisone or equivalent) and still use the above drugs within 2 weeks prior to enrollment.
3. Patients who are known to be previously allergic to macromolecular protein preparations or any component of SHR-1210.
4. Patients with clinically symptomatic metastases to central nervous system (e.g., cerebral edema requiring hormonal intervention, or progression of brain metastasis). Patients who have received treatment for brain or meningeal metastasis can be included if they are clinically stable (MRI) for at least 2 months and have discontinued systemic hormonal therapy (\> 10 mg/day prednisone or equivalent) for more than 2 weeks.
5. Patients who have previously received radiotherapy, chemotherapy, hormone therapy, surgery or molecular targeted therapy with an interval of less than 4 weeks from the completion of the treatment to the study medication (for patients who have previously received chemotherapy with nitrosourea or mitomycin, the interval from the end of chemotherapy to the study enrollment is less than 6 weeks); patients whose adverse events caused by previous treatments have not recovered to CTCAE Grade ≤ 1.
6. Patients with active infection or unexplained fever \> 38.5 °C during screening or prior to the first dose (patients with tumor-induced fever may be enrolled as per the judgment of the investigator).
7. Patients with congenital or acquired immunodeficiency (such as HIV, HBV, or HCV).
8. Patients who have previously received other PD-1 antibody treatments or immunotherapies targeting PD-1/PD-L1.

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: From the time the participants signed the informed consent to 90 days after the final dose (Up to 3 years and 9 months)
measure: Number of Participants Experiencing Severe AEs (SAEs)
timeFrame: From the time the participants signed the informed consent to 90 days after the final dose (Up to 3 years and 9 months)
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) For SHR-1210
timeFrame: PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 9 months).
measure: Area Under the Serum Concentration-time Curve to infinite time (AUC 0-inf) for SHR-1210
timeFrame: PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 9 months).
measure: Area Under the Serum Concentration-time Curve from dosing to the time of the last measured concentration (AUC 0-last) for SHR-1210
timeFrame: PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 9 months).
measure: Time to Maximum Concentration (Tmax) for SHR-1210
timeFrame: PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 9 months).
measure: Half-life (T½) for SHR-1210
timeFrame: PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 9 months).
measure: Clearance (Cl) for SHR-1210
timeFrame: PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 9 months).
measure: Volume of distribution (Vd) for SHR-1210
timeFrame: PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 9 months).
measure: Mean Residence Time (MRT) for SHR-1210
timeFrame: PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 9 months).
measure: C(ss, Max) of SHR-1210 after Multiple Dosing
timeFrame: PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 9 months).
measure: C(ss, Min) of SHR-1210 after Multiple Dosing
timeFrame: PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 9 months).
measure: Accumulation ratio based on Cmax (Rac, Cmax) of SHR-1210 after Multiple Dosing
timeFrame: PK blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 9 months).
measure: PD-1 receptor occupancy (RO) for SHR-1210
timeFrame: PD blood samples are collected multiple times on Cycle 1 (each cycle is 28 days) Day1, Day 8, Day 15, Day 22, Cycle 2 Day 1, Since Cycle 2, every 3 cycle Day 1, and the day disease progression (Up to 3 years and 9 months).
measure: Number of Participants with Anti-drug Antibodies (ADAs) for SHR-1210
timeFrame: Blood samples for ADAs analysis are collected on Cycle 1 (each cycle is 28 days) Day1 to the end of treatment (Up to 3 years and 9 months).
measure: Objective Response Rate (ORR)
timeFrame: Up to 3 years and 9 months
measure: Disease Control Rate (DCR)
timeFrame: Up to 3 years and 9 months
measure: Progression-free survival (PFS)
timeFrame: Up to 3 years and 9 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Affiliated to Beijing University
state: Beijing
Study officials:
affiliation: Jiangsu Hengrui Pharmaceutical Co., Ltd.
name: Yiding Xing, Doctor
role: STUDY_DIRECTOR
References:
citation: Zhou L, Wu X, Chi Z, Si L, Sheng X, Kong Y, Mao L, Lian B, Tang B, Yan X, Wang X, Bai X, Li S, Wei X, Li J, Yang Q, Guo J, Cui C. Safety, activity, and pharmacokinetics of camrelizumab in advanced Asian melanoma patients: a phase I study. BMC Cancer. 2022 May 20;22(1):565. doi: 10.1186/s12885-022-09663-5.