Abstract 131P
Background
Resistance to ICIs remains a challenge. HDAC inhibitors may synergize with PD-1 antibodies by inducing and activating NK cell and cytotoxic T cell (CTL) -mediated cellular immunity. Tislelizumab is an anti-PD-1 mAb approved for the treatment of NSCLC. Chidamide, a subtype-selective HDACi. This phase 2 study assessed antitumor activity and tolerability of chidamide and tislelizumab combined with chemotherapy in advanced NSCLC.
Methods
This was an open-label, prospective study. Patients with histologically or cytologically confirmed NSCLC (stage IIIB-IV) without prior systemic treatment was enrolled. EGFR/ALK mutation or fusion and symptomatic brain metastases were ineligible. Patients received chidamide 20 mg twice weekly orally, tislelizumab 200 mg Q3W intravenously, chemotherapy Q3W(≤4∼6 cycles) until unacceptable toxicity, withdrawal of consent, or death. The primary endpoint was ORR. Secondary endpoints include DCR、PFS and safety. Tumor response was assessed using RECIST V1.1.
Results
20 patients were enrolled in the study. At the data cut-off September 15, 2022, the median age was 63.5 years (range: 49-75) and all patients were male 90% of who with smoking history. Most patients were stage IV(95%) .40% of the patients whose PD-L1 expression was positive (PD-L1 TPS≥1%). The confirmed ORR was 73.7%(95%CI:63.6-83.8) and 1 patient was evaluated as CR. The DCR was 100%. The median follow-up was 10.7 months, median PFS was 13.8 months (95%CI:5.4m-22.2m) and 1-year PFS rate was 76.6% (95%CI:64.3%-88.9%). 11 patients (55.0%) had Grade ≥ 3 TRAEs. The most common Grade≥ 3 TRAEs were leukopenia (25.0%), neutropenia (20.0%) and thrombocytopenia (15%). Table: 131P
Incidence of TRAEs
| TRAEs (N=20) | Any Grade, n (%) | Grade ≥3, n(%) |
| Anemia | 15(75.0) | 2(10.0) |
| Alopecia | 12(60.0) | 0(0.0) |
| Neutropenia | 12(60.0) | 4(20.0) |
| leukopenia | 11(55.0) | 5(25.0) |
| Nausea | 9(45.0) | 0(0.0) |
| Thrombocytopenia | 9(45.0) | 3(15.0) |
| Increased ALT | 9(45.0) | 0(0.0) |
| Increased AST | 7(35.0) | 0(0.0) |
| Decreased appetite | 7(35.0) | 0(0.0) |
| Fatigue | 6(30.0) | 0(0.0) |
| Increased creatinine | 6(30.0) | 0(0.0) |
| Blood lipids increased | 5(25.0) | 1(5.0) |
| Constipation | 5(25.0) | 0(0.0) |
| Diarrhea | 5(25.0) | 2(10.0) |
| Pneumonia | 4(20.0) | 1(5.0) |
| Hypoesthesia | 3(15.0) | 0(0.0) |
| Adrenal insufficiency | 3(15.0) | 1(5.0) |
| Hypothyroidism | 2(10.0) | 0(0.0) |
| Hyperglycemia | 2(10.0) | 1(5.0) |
| Dermatitis | 1(5.0) | 1(5.0) |
Conclusions
Adding HDACi(Chidamide) plus Tislelizumab combined with chemotherapy showed encouraging antitumor activity and a favorable safety profile as first-line therapy for advanced NSCLC. Efficacy and safety of the combination will be continuously monitored.
Clinical trial identification
ChiCTR2000041542; Date of Registration: 2020.12.28.
Legal entity responsible for the study
The authors.
Funding
BeiGene (Beijing) Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.