A Phase Ib/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Initial Efficacy of Recombinant Humanized Anti-BTLA Monoclonal Antibody (JS004) Injection Combined With Toripalimab and With Standard Chemotherapy in Patients With Advanced Lung Cancer
Overview
- Phase
- Phase 1
- Intervention
- Recombinant humanized anti-BTLA monoclonal antibody (JS004) injection
- Conditions
- Advanced Lung Cancer
- Sponsor
- Shanghai Junshi Bioscience Co., Ltd.
- Enrollment
- 119
- Locations
- 1
- Primary Endpoint
- Incidence of SAEs
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
This is an open-label phase Ib/II clinical study to evaluate the safety, tolerability, pharmacokinetics and initial efficacy of JS004 injection combined with toripalimab and with or without standard chemotherapy in patients with advanced lung cancer
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects are eligible for the study if they meet all of the following criteria:
- •Sign the informed consent form voluntarily;
- •Males or females ≥18 years at the time of signing the informed consent;
- •Expected survival ≥3 months;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 ;
- •Pathologically confirmed locally advanced, metastatic or recurrent non-small cell lung cancer (NSCLC), which is currently not suitable for local treatment such as radical surgery or radiotherapy; For subjects with non-squamous carcinoma, there is no EGFR sensitive mutation or ALK fusion; for subjects with squamous carcinoma, genetic testing is not mandatory
- •Pathologically confirmed extensive-stage small cell lung cancer (ES-SCLC, according to the Veterans Administration Lung Study Group (VALG) staging), previously received no systemic anti-tumor therapy for ES-SCLC (Cohort 5); Subjects with limited-stage SCLC who have previously received systemic anti-tumor therapy cannot be enrolled;
- •The subject has at least one measurable lesion as a target lesion (RECIST v1.1 criteria,);
- •The subject agrees to provide tumor tissue samples ;
- •The subject has good organ function as indicated by screening laboratory results:
Exclusion Criteria
- •Subjects who met any of the following criteria will be excluded from the study:
- •For the third line and second line populations with advanced lung squamous carcinoma (Cohorts 1 and 2), subjects who have received systemic anti-tumor therapy within 3 weeks before the first dose of study drug, including: chemotherapy, targeted therapy, anti-vascular drug therapy, biological therapy, immunotherapy, radiotherapy or other treatments with investigational products
- •Any adverse reactions caused by previous treatments have not recovered to CTCAE (Version 5.0) Grade 1 or below ;
- •Symptomatic metastases to central nervous system.;
- •Subjects with poorly controlled tumor-related pain who require analgesic treatment must receive the treatment at a stable dose before participating in the study;
- •Hydrothorax or ascites or pericardial effusion with clinical symptoms or unstable condition after symptomatic treatment;
- •Subjects previously discontinued treatment due to PD-1/PD-L1 inhibitor toxicity;
- •Known history of severe allergic reactions to JS004 or toripalimab and its components, scheduled chemotherapeutic drugs and their components;
- •Known active or suspected autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease;
- •History of interstitial lung disease or drug-induced interstitial lung disease or pulmonitis;
Arms & Interventions
Cohort 1
NSCLC-squamous carcinoma third line;JS004 200mg + JS001 240mg Q3w, maintained until disease progression
Intervention: Recombinant humanized anti-BTLA monoclonal antibody (JS004) injection
Cohort 1
NSCLC-squamous carcinoma third line;JS004 200mg + JS001 240mg Q3w, maintained until disease progression
Intervention: Toripalimab
Cohort 2
NSCLC-squamous carcinoma second line;JS004 200mg + JS001 240 mg + docetaxel Q3w, maintained until disease progression
Intervention: Recombinant humanized anti-BTLA monoclonal antibody (JS004) injection
Cohort 2
NSCLC-squamous carcinoma second line;JS004 200mg + JS001 240 mg + docetaxel Q3w, maintained until disease progression
Intervention: Toripalimab
Cohort 2
NSCLC-squamous carcinoma second line;JS004 200mg + JS001 240 mg + docetaxel Q3w, maintained until disease progression
Intervention: Docetaxel
Cohort 3
NSCLC-non-squamous carcinoma first line;JS004 200mg + JS001 240 mg + pemetrexed + carboplatin/cisplatin Q3w, for 4 cycles;JS004 200mg + JS001 240 mg + pemetrexed, maintained until disease progression
Intervention: Recombinant humanized anti-BTLA monoclonal antibody (JS004) injection
Cohort 3
NSCLC-non-squamous carcinoma first line;JS004 200mg + JS001 240 mg + pemetrexed + carboplatin/cisplatin Q3w, for 4 cycles;JS004 200mg + JS001 240 mg + pemetrexed, maintained until disease progression
Intervention: Toripalimab
Cohort 3
NSCLC-non-squamous carcinoma first line;JS004 200mg + JS001 240 mg + pemetrexed + carboplatin/cisplatin Q3w, for 4 cycles;JS004 200mg + JS001 240 mg + pemetrexed, maintained until disease progression
Intervention: Pemetrexed
Cohort 3
NSCLC-non-squamous carcinoma first line;JS004 200mg + JS001 240 mg + pemetrexed + carboplatin/cisplatin Q3w, for 4 cycles;JS004 200mg + JS001 240 mg + pemetrexed, maintained until disease progression
Intervention: Cisplatin
Cohort 3
NSCLC-non-squamous carcinoma first line;JS004 200mg + JS001 240 mg + pemetrexed + carboplatin/cisplatin Q3w, for 4 cycles;JS004 200mg + JS001 240 mg + pemetrexed, maintained until disease progression
Intervention: Carboplatin
Cohort 4
NSCLC-squamous cell carcinoma first line;JS004 200mg + JS001 240 mg + paclitaxel + carboplatin Q3w, for 4 cycles; JS004 200mg + JS001 240 mg, maintained until disease progression
Intervention: Recombinant humanized anti-BTLA monoclonal antibody (JS004) injection
Cohort 4
NSCLC-squamous cell carcinoma first line;JS004 200mg + JS001 240 mg + paclitaxel + carboplatin Q3w, for 4 cycles; JS004 200mg + JS001 240 mg, maintained until disease progression
Intervention: Toripalimab
Cohort 4
NSCLC-squamous cell carcinoma first line;JS004 200mg + JS001 240 mg + paclitaxel + carboplatin Q3w, for 4 cycles; JS004 200mg + JS001 240 mg, maintained until disease progression
Intervention: Carboplatin
Cohort 4
NSCLC-squamous cell carcinoma first line;JS004 200mg + JS001 240 mg + paclitaxel + carboplatin Q3w, for 4 cycles; JS004 200mg + JS001 240 mg, maintained until disease progression
Intervention: Paclitaxel
Cohort 5
SCLC first line;JS004 200mg + JS001 240 mg + etoposide + carboplatin/cisplatin Q3w, for 4 cycles; JS004 200mg + JS001 240 mg, maintained until disease progression
Intervention: Recombinant humanized anti-BTLA monoclonal antibody (JS004) injection
Cohort 5
SCLC first line;JS004 200mg + JS001 240 mg + etoposide + carboplatin/cisplatin Q3w, for 4 cycles; JS004 200mg + JS001 240 mg, maintained until disease progression
Intervention: Toripalimab
Cohort 5
SCLC first line;JS004 200mg + JS001 240 mg + etoposide + carboplatin/cisplatin Q3w, for 4 cycles; JS004 200mg + JS001 240 mg, maintained until disease progression
Intervention: Cisplatin
Cohort 5
SCLC first line;JS004 200mg + JS001 240 mg + etoposide + carboplatin/cisplatin Q3w, for 4 cycles; JS004 200mg + JS001 240 mg, maintained until disease progression
Intervention: Carboplatin
Cohort 5
SCLC first line;JS004 200mg + JS001 240 mg + etoposide + carboplatin/cisplatin Q3w, for 4 cycles; JS004 200mg + JS001 240 mg, maintained until disease progression
Intervention: Etoposide
Outcomes
Primary Outcomes
Incidence of SAEs
Time Frame: 2 years
Incidence of serious adverse events (SAEs)
Incidence of adverse events (AEs)
Time Frame: 2 years
Incidence of adverse events (AEs)
ORR
Time Frame: 2 years
Efficacy endpoint: objective response rate (ORR) based on RECIST v1.1 criteria
Incidence of irAEs
Time Frame: 2 years
Incidence of immune-related adverse events (irAEs)
Secondary Outcomes
- titer of ADA(2 years)
- time to response (TTR)(2 years)
- PFS(2 years)
- 1-year OS rate(1 year)
- incidence of ADA(2 years)
- incidence of Nab(2 years)
- DOR(2 years)
- titer of Nab(2 years)
- DCR(2 years)
- OS(2 years)
- Drug concentration in plasma(2 years)