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SCT-I10A or Placebo Plus Docetaxel With Previously Treated Squamous Cell Non-small Cell Lung Cancer

Phase 3
Terminated
Conditions
Squamous-cell Non-Small-cell Lung Cancer
Interventions
Registration Number
NCT04171284
Lead Sponsor
Sinocelltech Ltd.
Brief Summary

This is a phase 3 double-blinded randomized multicenter clinical trial of SCT-I10A or placebo plus docetaxel with previously treated squamous cell non-small cell lung cancer patients. The main endpoint is to compare the overall survival (OS) of these two regimens above.

Detailed Description

In 2015, there were near 787,000 patients diagnosed with lung cancer in China. And in the very same year, 631,000 lung cancer patients died of the disease. Lung cancer still causes most cancer related death in here. Approximately 85% of lung cancer is non-small cell lung cancer (NSCLC) compared with small cell lung cancer (\~15%) pathologically. NSCLC include squamous cell NSCLC, adenocarcinoma and large cell carcinoma. Although there are therapies developed to treat the condition, patients with advanced squamous-cell (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options in China. Hence, we developed a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor monoclonal antibody (SCT-I10A) which inhibits the interaction between PD-1 and its ligands results in the reactivation of active T cell and finally leads to caner immunotherapy. We are now carrying out a phase 3 clinical trial to determine whether SCT-I10A plus docetaxel surpass docetaxel monotherapy with previously treated squamous-cell NSCLC patients. As designed in the protocol, 360 eligible subjects would be randomized into two arms in a ratio of 2:1. 240 subjects would be treated with SCT-I10A plus docetaxel in the experimental arm while 120 subjects would be treated with placebo plus docetaxel in the active comparator arm. Both of these arms will be treated with maintenance therapy after planed treatments. Our primary endpoint is overall survival, secondary endpoints are PFS, OSR, ORR, DOR, DCR and other efficacy and safety index.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
188
Inclusion Criteria
  1. Patients should be voluntarily sign the written informed consent.
  2. Histologically or cytologically confirmed diagnosis of locally advanced or metastatic squamous NSCLC. Or recurrent squamous NSCLC according UICC/AJCC 8th edition.
  3. At least one measurable tumor lesion per RECIST 1.1 criteria. A lesion previously irradiated could be considered as a target lesion only in the condition that progression occurred at the time of 3 months after the end of radiotherapy.
  4. Previously treated with one platinum based regimen (including platinum and endostar regimen) and progression occur during or after treatment or unbearable treatment related adverse events.
  5. Progression after EGFR-TKIs in patients with driver gene mutation.
  6. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
Exclusion Criteria
  1. Patient who is allergic to recombinant humanized PD-1 monoclonal antibody or the components of the drug.
  2. Patient who is allergic to taxane.
  3. Previously treated with any of the antibodies targeted on PD-1, PD-L1, PD-2, CD137, CTLA-4, T cell, co-stimulation or drugs targeted on the checkpoint signal pathway.
  4. Previously treated with docetaxel.
  5. The histopathological subtype is not squamous cell non-small cell lung cancer, or squamous cell < 90% in a mixed carcinoma.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SCT-I10A plus DocetaxelSCT-I10SCT-I10A 200mg, I.V., Q3W; Docetaxel 70-75 mg per square meters of body surface area,I.V., Q3W. Maximum of 6 cycles
SCT-I10A plus DocetaxelDocetaxelSCT-I10A 200mg, I.V., Q3W; Docetaxel 70-75 mg per square meters of body surface area,I.V., Q3W. Maximum of 6 cycles
Placebo puls docetaxelPlaceboPlacebo 200mg, I.V., Q3W; Docetaxel 70-75 mg per square meters of body surface area,I.V., Q3W Maximum of 6 cycles
Maintenance therapy of SCT-I10ASCT-I10Subjects complete 2-6 cycles of combined therapies, when the evaluation result is CR, PR or SD (RECIST 1.1), the subjects will enter maintain therapy: SCT-I10A 200mg, I.V., Q3W, till progression, loss to follow-up, new antineoplastic therapy or intolerable toxicity.
Maintenance therapy of PlaceboPlaceboSubjects complete 2-6 cycles of combined therapies, when the evaluation result is CR, PR or SD (RECIST 1.1), the subjects will enter maintain therapy: Placebo 200mg, I.V., Q3W, till progression, loss to follow-up, new antineoplastic therapy or intolerable toxicity.
Placebo puls docetaxelDocetaxelPlacebo 200mg, I.V., Q3W; Docetaxel 70-75 mg per square meters of body surface area,I.V., Q3W Maximum of 6 cycles
Primary Outcome Measures
NameTimeMethod
Overall survivalUp to approximately 3 years

OS is the time from the date of randomization to death due to any cause.

Secondary Outcome Measures
NameTimeMethod
The concentration of anti-SCT-I10A antibodies in the serum of subjectsUp to approximately 3 years

The concentration of anti-SCT-I10A antibodies in the serum of subjects during or after the study treatments will be measured, its level could indicate the immunogenicity of SCT-I10A.

The expression level of PD-L1 of subjects' specimensUp to approximately 3 years

The expression level of PD-L1 of the subjects would be measure by immunohistochemical detection. The results would be used to analyze the correlation of PD-L1 level and outcomes including primary and secondary endpoints including OS, PFS, OSR, ORR, DOR and DCR.

Cancer-specific quality of life of the regimens treated subjectsUp to approximately 3 years

European Organisation for Research and Treatment of Cancer (EORTC) cancer-specific quality of life questionnaire (EORTC QLQ-C30) will be applied in all subjects to collect the score of 30 items of subjects before and after study treatments. For the items from one to twenty-eight, the minimum and maximum scores are 28 and 112 respectively and the higher score means a worse outcome. For the items from twenty-nine to thirty, the minimum and maximum raw scores are 2 and 14 respectively and the higher score means a better outcome. Further analysis could be done based on the calculation.

Lung cancer-specific quality of life of the regimens treated subjectsUp to approximately 3 years

European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) will be applied in all subjects to collect the score of 13 specific typical symptoms of lung cancer patients before and after study treatments. The minimum and maximum raw scores are 12 and 52 respectively, the higher score means a worse outcome.

ORRUp to approximately 3 years

ORR is the proportion of subjects with CR or PR based on RECIST v1.1.

OSR of 6 months, 12 months and 18 mothsEach subject that randomized will be followed up for 18 months to measure the OSR.

overall survival rate from the date of randomization till the 6 months,12 months and 18 months

PFSUp to approximately 3 years

PFS is defined as the time from the date of randomization till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).

DORUp to approximately 3 years

DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.

DCRUp to approximately 3 years

DCR is defined as the proportion of subjects with CR, PR, or SD based on RECIST v1.1.

Trial Locations

Locations (1)

Shanghai Chest Hospital

🇨🇳

Shanghai, Shanghai, China

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