A Single-arm, Phase II Clinical Study of Toripalimab Combined With Cryoablation for First-line Oligo-progression in Driver-negative Advanced NSCLC
Overview
- Phase
- Phase 2
- Intervention
- Toripalimab
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- Shanghai Chest Hospital
- Enrollment
- 54
- Locations
- 3
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
Immunotherapy with programmed death-1(PD-1) inhibitors is now standard therapy for first-line use in patients with driver-negative advanced NSCLC, whether as single-agent or in combination with chemotherapy. After progression of first-line immunotherapy, NSCLC patients may be treated with chemotherapy, radiotherapy or targeted therapies, among others. Recently, Immune Checkpoint inhibitors (ICIs) rechallenge has become a highly anticipated option. Although the objective response rate of the ICIs rechallenge patients has decreased substantially compared with the efficacy of the first ICI treatment, nearly 50% of patients can regain disease control.
Cryoablation is a minimally invasive technique that utilizes very low temperature to eliminate viable tumour cells in target tissues. It has been reported that ablation can enhance immune response.
The objective of this study was to evaluate the efficacy and safety of toripalimab (PD-1) in combination with cryoablation in the treatment of oligometastatic driver-negative advanced NSCLC after first-line immunotherapy progress.
Investigators
Ziming Li
Deputy Director
Shanghai Chest Hospital
Eligibility Criteria
Inclusion Criteria
- •Voluntary participation and written informed consent;
- •histologically or cytologically confirmed advanced metastatic (stage IV) non-small cell lung cancer;
- •Patients with negative driver genes who develop oligoprogression after receiving standard first-line therapy. The oligoprogression is defined as: 1-5 metastatic lesions, and no more than 3 organs;
- •Age 18-75 years old; ECOG PS: 0-1; The expected survival is more than 3 months;
- •At least one measurable lesion;
- •Patients were willing to provide adequate blood and tissue samples；
- •Patients had adequate hematologic, renal, and liver function;
- •International normalised ratio (INR) ≤1.5 and partial thromboplastin time (PTT or aPTT) ≤1.5 x ULN within 7 days prior to study treatment;
- •The woman patients of childbearing age who must agree to take contraceptive methods during the research;
- •The man patients who must agree to take contraceptive methods during the research and within another 6 months after it.
Exclusion Criteria
- •cytologically or histologically confirmed combination with small cell lung cancer component or sarcomatoid element;
- •Previously received targeted therapy for advanced NSCLC (including osimertinib, erlotinib, crizotinib, etc);
- •Had undergone major surgical operations or had not fully recovered from previous operations within 3 weeks before enrollment;
- •Known active nervous system (CNS) metastases and/or carcinomatous meningitis;
- •Spinal cord compression for which operation and/or radical radiotherapy has not been given, or no clinical evidence of stable disease for ≥4 weeks prior to enrollment after treatment for previously diagnosed spinal cord compression;
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; patients with stable symptoms after drainage can be enrolled;
- •History of idiopathic pulmonary fibrosis, organized pneumonia (e.g., obliterating bronchiolitis), drug induced pneumonia, idiopathic pneumonia or evidence of active pneumonia during chest CT scanning for screening;
- •Clinically uncontrolled active infection, including but not limited to acute pneumonia;
- •Uncontrollable major epileptic seizure or superior vena cava syndrome;
- •Previous or current co-occurrence of other malignancies (excluding controllable non-melanoma basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the breast or cervix, superficial bladder cancer, or other carcinoma in situ);
Arms & Interventions
Toripalimab Combined with Cryoablation
Patients with oligometastatic driver-negative advanced NSCLC after first-line immunotherapy progress would be treated with Toripalimab Combined with Cryoablation.
Intervention: Toripalimab
Toripalimab Combined with Cryoablation
Patients with oligometastatic driver-negative advanced NSCLC after first-line immunotherapy progress would be treated with Toripalimab Combined with Cryoablation.
Intervention: Cryoablation
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: 6 months
PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or date of death, whichever occurred first.
Secondary Outcomes
- Objective Response Rate (ORR)(6 months)
- Disease control rate (DCR)(6 months)
- Overall Survival (OS)(24 months)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](Up to 2 years)
- Correlation analysis of PD-L1 expression of tumor and ORR(Up to 1 years)