Head and Neck Squamous Cell Carcinom, Nasopharyngeal Carcinoma
Conditions
Brief summary
A phase I/II clinical study of JS004 in subjects with head and neck cancer in China, to evaluate the safety, tolerability, PK, immunogenicity, antitumor activity and biomarkers of JS004, define the RP2D. A cycle is 21 days (3 weeks) which includes JS004 being administered IV Q3W and JS004 combine with JS001 being administered IV Q3W. All patients will be treated until disease progression per RECIST v1.1 and iRECIST, or intolerable toxicity per CTCAE 5.0, withdrawal of consent, or end of the study, whichever occurs first.Disease progression must be confirmed at least 4 weeks but no longer than 8 weeks after initial documentation of progression.
Interventions
200mg:JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion
BIOLOGICALJS001 and JS004
Part B: 100mg JS004 + 240mg JS001 or 200mg JS004+ 240mg JS001
Sponsors
Shanghai Junshi Bioscience Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1.Males and females ≥ 18 and ≤ 80 years of age; 2.Recurrent or metastatic squamous cell carcinoma of the head and neck and nasopharyngeal carcinoma confirmed histologically or cytologically are no longer suitable for local treatment such as surgery or radiotherapy； 3.Has received at least a first-line standard regimen for relapsed and metastatic disease and has progressed during or after treatment; 4.The Eastern Cooperative Oncology Group (ECOG) had a physical status score of 0 or 1. 5.Life expectancy ≥12 weeks; 6.At least one measurable lesion per RECISTv1.1 and iRECIST; 7.Willingness to provide consent for fresh pre-treatment biopsies, or,an archival specimen could be required within two years prior to the first dose of study drug; 8.Adequate organ and marrow function per protocol specifically defined; 9.Females of childbearing potential ,and males who are sexually active with a female partner of childbearing potential, must use effective contraception from time of screening, and must agree to continue using such precautions for 60 days after the final dose of JS004; 10.All acute toxic reactions caused by previous anti-tumor therapy, surgery or radiotherapy were alleviated to grade 0-1 (according to NCI-CTCAE version 5.0) or to the level specified by the inclusion/
Exclusion criteria
.Except for hair loss, pigmentation, or other toxicity that the researcher believes does not pose a safety risk to the subject, and does not affect treatment compliance. 11.Able to understand and willing to sign the Informed Consent Form;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of adverse events (AE) and serious adverse events (SAE) were assessed | 2 years | Incidence and severity of adverse events (AE) and serious adverse events (SAE) as assessed according to NCI-CTCAE 5.0, as well as abnormalities in vital signs, electrocardiogram, and laboratory tests |
| ORR evaluated according to RECIST 1.1 | 2 years | Objective Response Rate(ORR) evaluated according to RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS | 2 years | Overall survival |
| PFS | 2 years | Progression-free survival evaluated according to RECIST 1.1 |
| 6-month OS rate | 6 months | 6-month overall survival rate |
| Phase II Recommended Dose of JS004 (RP2D-A) and JS004 combined with JS001(RP2D-B) | 2 years | Phase II Recommended Dose of JS004 (RP2D-A) and JS004 combined with JS001(RP2D-B) |
| DCR | 2 years | Disease Control Rate (DCR) |
| ADA/Nab rate | 2 years | the rate of Anti-drug body (ADA) and neutralizing antibody (Nab) |
| Cmax | 2 years | Maximum Plasma Concentration(Cmax) after injection of JS004 |
| DOR | 2 years | Duration of Response |
Other
| Measure | Time frame | Description |
|---|---|---|
| AUC | 2 years | Area Under the Cure(AUC) after injection of JS004 |
| t1/2 | 2 years | t1/2 after injection of JS004 |
| Plasma Clearence(CL) | 2 years | Plasma Clearence(CL) after injection of JS004 |
| volume of distribution of steady state(Vss) | 2 years | volume of distribution of steady state(Vss) after multiple dose injection of JS004 |
| Ctrough | 2 years | trough Plasma Concentration (Ctrough) after injection of JS004 |
| Predictive biomarkers | 2 years | Predictive biomarkers, including but not limited to, BTLA and HVEM |
| Tmax | 2 years | Perk Time(Tmax) after injection of JS004 |
Countries
China
Outcome results
None listed