Neoadjuvant Therapy With Toripalimab and JS004 Combined With Platinum-based Doublet Chemotherapy for Resectable or Potentially Resectable Stage III Non-small Cell Lung Cancer: A Randomised Controlled, Open-label, Phase 2 Trial
Overview
- Phase
- Phase 2
- Intervention
- Toripalimab
- Conditions
- Stage III Non-small Cell Lung Cancer
- Sponsor
- Shanghai Pulmonary Hospital, Shanghai, China
- Enrollment
- 124
- Primary Endpoint
- Pathologic complete response (PCR) rate
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
For stage III non-small cell lung cancer (NSCLC), neoadjuvant chemotherapy plus PD-1 antibody is recommended. However, most patients could not achieve complete pathological response (CPR). New immunotherapeutic strategy is needed to achieve higher CPR rate. JS004 is a new antibody targeting B and T lymphocyte attenuator (BTLA) which restrains the function of immune cells and leads to immune escape of tumor cells. The combination of PD-1 antibody and BTLA antibody has shown good therapeutic effect in solid tumors. This trial aims to investigate the efficacy and safety of the therapeutic regimen of toripalimab and JS004 plus chemotherapy in stage III NSCLC.
Investigators
Peng Zhang
Professor
Shanghai Pulmonary Hospital, Shanghai, China
Eligibility Criteria
Inclusion Criteria
- •The patient shall sign the Informed Consent Form.
- •Aged 18 ≥ years.
- •Histological or cytological diagnosis of NSCLC by needle biopsy, and stage IIIB-IIIC confirmed by imageological examinations (CT, PET-CT or EBUS).
- •Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or
- •Life expectancy is at least 12 weeks.
- •At least 1 measurable lesion according to RECIST 1.
- •Patients with good function of other main organs (liver, kidney, blood system, etc.)
- •Patients with lung function can tolerate surgery;
- •Without systematic metastasis (including M1a, M1b and M1c);
- •Fertile female patients must voluntarily use effective contraceptives not less than 120 days after chemotherapy or the last dose of toripalimab (whichever is later) during the study period, and urine or serum pregnancy test results within 7 days prior to enrollment are negative.
Exclusion Criteria
- •Participants who have received any systemic anti-cancer treatment for thymic epithelial tumor, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment and experimental treatment;
- •Participants with any unstable systemic disease (including active infection, uncontrolled hypertension), unstable angina pectoris, angina pectoris starting in the last three months, congestive heart failure (\>= NYHA) Grade II), myocardial infarction (6 months before admission), severe arrhythmia requiring drug treatment, liver, kidney or metabolic diseases;
- •With activate or suspectable autoimmune disease, or autoimmune paracancer syndrome requiring systemic treatment;
- •Participants who are allergic to the test drug or any auxiliary materials;
- •Participants with Interstitial lung disease currently;
- •Participants with active hepatitis B, hepatitis C or HIV;
- •Pregnant or lactating women;
- •Participants suffering from nervous system diseases or mental diseases that cannot cooperate;
- •Participated in another therapeutic clinical study;
- •Other factors that researchers think it is not suitable for enrollment.
Arms & Interventions
Safety run-in arm
In this arm, 6 patients with resectable or potentially resectable stage III non-small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Toripalimab
Safety run-in arm
In this arm, 6 patients with resectable or potentially resectable stage III non-small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: JS004
Safety run-in arm
In this arm, 6 patients with resectable or potentially resectable stage III non-small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Pemetrexed
Safety run-in arm
In this arm, 6 patients with resectable or potentially resectable stage III non-small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Nab-paclitaxel
Safety run-in arm
In this arm, 6 patients with resectable or potentially resectable stage III non-small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Carboplatin
Safety run-in arm
In this arm, 6 patients with resectable or potentially resectable stage III non-small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Surgery
JS004 arm
Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Toripalimab
JS004 arm
Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: JS004
JS004 arm
Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Pemetrexed
JS004 arm
Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Nab-paclitaxel
JS004 arm
Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Carboplatin
JS004 arm
Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Surgery
Control arm
Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Toripalimab
Control arm
Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Pemetrexed
Control arm
Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Nab-paclitaxel
Control arm
Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Carboplatin
Control arm
Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.
Intervention: Surgery
Outcomes
Primary Outcomes
Pathologic complete response (PCR) rate
Time Frame: Up to 30 months
PCR rate is defined as the proportion of participants who have achieved pathologic complete response (on routine hematoxylin and eosin staining, no tumor cell can be found in tumor bed or lymph node) in all participants.
Secondary Outcomes
- Treatment-related adverse event (TRAE)(Up to 30 months)
- Objective response rate (ORR)(up to 30 months)
- Rate of conversion from potentially resectable to resectable(Up to 30 months)
- EORTC-QLQ-L13 scale(up to 5 months)
- EORTC-QLQ-C30 scale(up to 5 months)
- R0 resection rate(Up to 30 months)
- Event-free survival (EFS)(up to 60 months)
- Major pathologic response (MPR) rate(Up to 30 months)
- Overall survival (OS)(up to 60 months)