Clinical trial NCT06505837: JS001sc or JS001 Plus Chemotherapy is Indicated for Relapsed or Metastatic First-Line Non-Squamous Non Small Cell Lung Cancer（NSCLC）
Official title: Open-Label, Randomized, Phase III Clinical Study Comparing the Pharmacokinetic Profile, Efficacy, and Safety of JS001sc and JS001 in Combination With Standard Chemotherapy as First-Line Treatment for Recurrent Metastatic Non-Squamous Non Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Recurrent Metastatic Non-Squamous Non Small Cell Lung Cancer
Lead sponsor: Shanghai Junshi Bioscience Co., Ltd.
Sponsor class: OTHER
Collaborators: name: Sponsor GmbH
First posted: 2024-07-17
Enrollment: 356
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-Lable, randomized, phase III clinical study to compare the pharmacokinetic profile, efficacy, and safety of Toripalimab injection (subcutaneous) (JS001sc) and Toripalimab injection (JS001) in combination with standard chemotherapy as first-line treatment for recurrent or metastatic Non-Squamous Non small cell lung cancer

Detailed description: A randomized, open-label,multicenter, phase III clinical study was designed to enroll 356 participants with recurrent or metastatic Non-Squamous Non small cell lung cancer without EGFR sensitive mutations or ALK fusion. They will be randomly assigned in a 1:1 ratio to one of two treatment groups:Group A: JS001sc+ platinum-based chemotherapy；JS001sc, 360 mg, was administered subcutaneously (SC) once every 3 weeks (Q3W)；Chemotherapy: pemetrexed + carboplatin/cisplatin, Q3W, up to 4 cycles, non-progressive subjects pemetrexed monotherapy maintenance therapy. Group B: JS001+ platinum-based chemotherapy；JS001, 240 mg, IV, Q3W；Chemotherapy: pemetrexed + carboplatin/cisplatin, Q3W, up to 4 cycles, non-progressive subjects pemetrexed monotherapy maintenance therapy. Both groups were treated until treatment termination criteria were met.

Eligibility criteria: Inclusion criteria：

1. Age ≥18 years at the time of signing informed consent, both male and female.
2. Histologically or cytologically confirmed relapsed or metastatic non-squamous NSCLC.
3. Proof of no detection of EGFR-sensitive mutations and ALK fusions.
4. No prior systemic anti-tumor therapy for advanced or metastatic non-squamous NSCLC. Subjects who have received adjuvant therapy or neoadjuvant therapy (chemotherapy, radiotherapy, or other treatments) for recurrent non-squamous NSCLC can be enrolled if the interval between the last treatment and recurrence is more than 6 months.
5. Subject has at least 1 measurable lesion according to RECIST v1.1 criteria.
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
7. Expected survival ≥ 12 weeks.
8. The function of vital organs meets the following requirements (Note: no blood components and hematopoietic growth factors are allowed to be used within 14 days before screening);

   1. Absolute neutrophil count (ANC) ≥1.5×109/L
   2. Platelet ≥ 100×109/L;
   3. Hemoglobin ≥9 g/dL;
   4. Bilirubin ≤1.5× upper limit of normal (ULN);
   5. Alanine aminotransferase (ALT) ≤ 2.5× ULN, aspartate aminotransferase (AST) ≤ 2.5× ULN;
   6. Creatinine clearance (CrCL) ≥ 60 mL/min (cisplatin) or CrCL ≥50 mL/min (carboplatin) (Cockcroft-Gault formula);
   7. Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, International normalized ratio (INR) ≤ 1.5 (for prophylactic anticoagulation at stable doses, drug-specific monitoring requirements are acceptable beyond this range).
9. Female subjects of childbearing potential, as well as male subjects whose partner is a female of childbearing potential, are required to use a highly effective contraceptive method for the duration of study treatment and for at least 6 months after the last treatment.
10. Voluntarily join this study, sign the informed consent form, have good compliance, and cooperate with follow-up plan.

Exclusion criteria：

1. Concomitant study disease states of:

   1. Histological or cytological pathology of the tumor confirmed with small cell lung cancer component or sarcomatoid lesion, or squamous cell carcinoma component \>10%;
   2. Patients with known meningeal metastases;
   3. Patients with untreated brain metastases, who have received radiation therapy for brain metastases and are judged by the investigator to be stable brain metastases can be enrolled, and the criteria for stability need to meet all of the following conditions: no symptoms related to brain metastases, corticosteroid therapy needs to be discontinued at least 7 days before study drug administration, and no disease progression is found after the end of treatment for brain metastases and before randomization imaging compared with pre-treatment imaging (at least 4 weeks apart);
   4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more frequently);
   5. Spinal cord compression that has not undergone radical treatment with surgery and/or radiotherapy, or previously diagnosed spinal cord compression that has no clinical evidence of stable disease for ≥ 4 weeks prior to enrollment after treatment;
2. Have received any of the following treatments:

   1. Received local small-area radiotherapy (such as palliative radiotherapy for bone metastases) within 14 days prior to the first study drug administration;
   2. Prior immune-mediated therapy, including but not limited to anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy (or any other antibodies acting on T cell synergistic stimulation or checkpoint pathways such as IDO, IL-2R, GITR);
   3. Receipt of any investigational drug within 4 weeks or 5 half-lives prior to the first dose of study drug, whichever is shorter;
   4. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study, or the subject is in the follow-up period of the interventional clinical study;
   5. Systemic therapy with corticosteroids (\> 10 mg prednisone equivalent dose per day) or other immunosuppressants within 2 weeks prior to the first dose of study drug. Inhaled or topical corticosteroids are permitted. Receipt of short-term corticosteroids (such as pre-intravenous contrast) within 2 weeks prior to the first dose of study drug is permitted;
   6. Subjects who have received proprietary Chinese medicines or immunomodulatory drugs with anti-tumor indications (thymus peptide, interferon, interleukin, etc.) within 2 weeks before the first dose of study drug, or who need to continue to receive these drugs during the study;
   7. Those who have been vaccinated with anti-tumor vaccines or have received live vaccines within 4 weeks before the first dose of study drug;
   8. Major surgery or severe trauma within 4 weeks prior to the first use of study drug.
3. Toxicity from previous anti-tumor therapy has not recovered to ≤ CTCAE grade 1 (except for toxicity judged by the investigator to have no safety risk);
4. Known hypersensitivity to any of the study treatments and their excipients;
5. Unable or unwilling to use folic acid or vitamin B12 injection;
6. Active autoimmune disease, history of autoimmune disease (including but not limited to interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism); except for:

   1. Subjects with vitiligo or cured childhood asthma/allergies that do not require any intervention after adulthood;
   2. Subjects with autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone;
   3. Subjects on stable doses of insulin for the treatment of type I diabetes mellitus;
7. Have a history of immunodeficiency, including a positive HIV test, or have other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation and allogeneic bone marrow transplantation, or autologous hematopoietic stem cell transplantation;
8. Severe infection (CTCAE\> grade 2) within 4 weeks before the first use of the study drug, such as severe pneumonia requiring hospitalization, infection comorbidities, etc., active lung inflammation on baseline chest imaging, symptoms and signs of infection within 2 weeks prior to the first dose of the study drug requiring oral or intravenous antibiotic treatment (except for prophylactic antibiotic use);
9. Confirmed or suspected history of interstitial lung disease or idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis, or other moderate to severe pulmonary diseases that seriously affect lung function (except for ≤ grade 1 radiation pneumonitis);
10. Subjects with active pulmonary tuberculosis infection found by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within 1 year prior to enrollment, or subjects with a history of active pulmonary tuberculosis infection more than 1 year ago but without formal treatment;
11. Presence of active hepatitis B (hepatitis B virus surface antigen (HBsAg) positive with HBV DNA ≥500 IU/mL), hepatitis C (hepatitis C antibody positive, and HCV-RNA above the lower limit of detection of the analytical method);
12. Diagnosis of any other malignancy prior to the first dose of study drug, with the exception of malignancies with low risk of metastasis (5-year survival rate \>90%), such as adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or breast, or adequately treated localized prostate cancer;
13. Pregnant or lactating women;
14. Uncontrolled intercurrent illness including, but not limited to: symptomatic congestive heart failure, left ventricular ejection fraction (LVEF) \<50%, uncontrolled hypertension, unstable angina, uncontrolled arrhythmia, major seizures, superior vena cava syndrome, or psychiatric illness/social situation that may affect study compliance, result in a significant increase in the risk of adverse events, or affect the subject's ability to provide written informed consent;
15. As judged by the investigator, the subject has other factors that may lead to the forced termination of the study, such as other serious diseases (including mental illnesses) requiring concomitant treatment, serious abnormalities in laboratory test values, and/or family or social factors that may affect the safety of the subject or the collection of experimental data.

Primary outcomes:
measure: Observed serum Ctrough at Cycle 1
timeFrame: the end of Cycle 1 (Each cycle is 21 days)
measure: Model-predicted area under the concentration-time curve(AUC) from 0 to 21 days at Cycle 1
timeFrame: the end of Cycle 1 (Each cycle is 21 days)
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: up to 2years
measure: Progression-free survival (PFS)
timeFrame: up to 2years
measure: 6-month progression-free survival(PFS) rate
timeFrame: up to 6-month
measure: Disease control rate (DCR)
timeFrame: up to 2years
measure: Duration of response (DoR)
timeFrame: up to 2years
measure: Safety: adverse events (AEs)
timeFrame: up to 2years
Other outcomes:
Locations:
city: Changshang
country: China
facility: Hunan Cancer Hospital
state: Hunan
Study officials:
affiliation: Medical director
name: Weihua Wang, doctorate
role: STUDY_DIRECTOR
References: