Neoadjuvant Therapy With Toripalimab and JS004 Combined With Etoposide and Platinum Chemotherapy for Limited-stage Small Cell Lung Cancer : A Single-arm, Phase 2 Trial
Overview
- Phase
- Phase 2
- Intervention
- JS004
- Conditions
- Limited Stage Small Cell Lung Cancer
- Sponsor
- Shanghai Pulmonary Hospital, Shanghai, China
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Pathologic complete response (PCR) rate
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
For limited-stage small cell lung cancer (SCLC), neoadjuvant chemotherapy plus PD-1 antibody is recommended. However, most patients cannot achieve a complete pathological response (CPR). A new immunotherapeutic strategy is needed to achieve a higher CPR rate. JS004 is a new antibody targeting B and T lymphocyte attenuator (BTLA), which restrains immune cells' function and leads to immune escape of tumor cells. The combination of PD-1 and BTLA antibodies has shown a good therapeutic effect in solid tumors. This trial aims to investigate the efficacy and safety of the therapeutic regimen of toripalimab and JS004 plus etoposide and platinum Chemotherapy in limited-stage SCLC.
Investigators
Peng Zhang
Director
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 SCLC by needle biopsy, and limited stage 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.)
- •Without systematic metastasis (including M1a, M1b and M1c);
- •Expected to be completely resected
- •Patients with lung function can tolerate surgery
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;
- •Patients with a malignancy other than SCLC within five years prior to the start of this trial;
- •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;
- •Any malabsorption;
- •Participants suffering from nervous system diseases or mental diseases that cannot cooperate
Arms & Interventions
Neoadjuvant Therapy With Toripalimab and JS004 Combined With Etoposide and Platinum Chemotherapy
In this arm, 30 patients with limited-stage small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with etoposide and platinum chemotherapy. And those resectable after neoadjuvant therapy will be treated with surgery. Postoperative patients receive two cycles of toripalimab and JS004 combined with etoposide and platinum chemotherapy. then patients received maintenance treatment with toripalimab and JS004 until the disease progressed.
Intervention: JS004
Neoadjuvant Therapy With Toripalimab and JS004 Combined With Etoposide and Platinum Chemotherapy
In this arm, 30 patients with limited-stage small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with etoposide and platinum chemotherapy. And those resectable after neoadjuvant therapy will be treated with surgery. Postoperative patients receive two cycles of toripalimab and JS004 combined with etoposide and platinum chemotherapy. then patients received maintenance treatment with toripalimab and JS004 until the disease progressed.
Intervention: Toripalimab
Neoadjuvant Therapy With Toripalimab and JS004 Combined With Etoposide and Platinum Chemotherapy
In this arm, 30 patients with limited-stage small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with etoposide and platinum chemotherapy. And those resectable after neoadjuvant therapy will be treated with surgery. Postoperative patients receive two cycles of toripalimab and JS004 combined with etoposide and platinum chemotherapy. then patients received maintenance treatment with toripalimab and JS004 until the disease progressed.
Intervention: surgery
Neoadjuvant Therapy With Toripalimab and JS004 Combined With Etoposide and Platinum Chemotherapy
In this arm, 30 patients with limited-stage small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with etoposide and platinum chemotherapy. And those resectable after neoadjuvant therapy will be treated with surgery. Postoperative patients receive two cycles of toripalimab and JS004 combined with etoposide and platinum chemotherapy. then patients received maintenance treatment with toripalimab and JS004 until the disease progressed.
Intervention: Etoposide
Neoadjuvant Therapy With Toripalimab and JS004 Combined With Etoposide and Platinum Chemotherapy
In this arm, 30 patients with limited-stage small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with etoposide and platinum chemotherapy. And those resectable after neoadjuvant therapy will be treated with surgery. Postoperative patients receive two cycles of toripalimab and JS004 combined with etoposide and platinum chemotherapy. then patients received maintenance treatment with toripalimab and JS004 until the disease progressed.
Intervention: Platinum
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
- Major pathologic response (MPR) rate(Up to 30 months)
- Objective response rate (ORR)(up to 30 months)
- Event-free survival (EFS)(up to 60 months)
- Overall survival (OS)(up to 60 months)
- Treatment-related adverse event (TRAE)(Up to 30 months)
- EORTC-QLQ-C30 scale(up to 5 months)