Tislelizumab Combined With Anlotinib and 2-cycles Irinotecan as Second Line Treatment of SCLC
Status:
Recruiting
Trial end date:
2023-06-01
Target enrollment:
Participant gender:
Summary
SCLC has short doubling time, high proliferation rate and early widespread metastasis. Most
patients with SCLC have hematogenous metastasis. SCLC is highly sensitive to initial
chemoradiotherapy, but the recurrence rate is high. The strategy for local limited SCLC
patients was chemotherapy plus chest radiotherapy; In patients with extensive stage SCLC,
first-line platinum-based chemotherapy has been established as the standard treatment for
patients with small cell lung cancer (SCLC) with better results. Although the initial
response to chemotherapy is high, it is easy to relapse and develop drug resistance.
In second-line therapy, the single-agent activity of multiple chemotherapy agents has been
demonstrated, but a higher incidence of grade 3-4 hematological adverse events In the Passion
study published by Wang Jie et al. [10], the efficacy and safety of the antiangiogenic drug
apatinib combined with carrizumab in the second-line treatment of small cell lung cancer were
investigated. A total of 59 patients were enrolled in the study. Of the 47 patients in the
extended phase, the confirmed ORR was 34.0% (95%CI 20.9-49.3), with a median PFS of 3.6
months and a median OS of 8.4 months In patients with platinum sensitivity and platinum
resistance, ORR was 37.5% vs 32.3%, MPFS was 3.6m vs 2.7m, and MOS was 9.6m vs 8.0m. Grade 3
treatment-related adverse events (TRAEs) occurred in 43 of the 59 patients (72.9%), and 5
patients (8.5%) were discontinued due to TRAEs. The combination regimen showed potential
antitumor activity in both platinum-sensitive and platinum-resistant cases.
The research and exploration of small cell lung cancer can learn from the research idea in
the field of non-small cell lung cancer. The Checkmate9LA study reported in 2020ASCO [11]
investigated the safety and efficacy of Nivolumab+2 cycle chemotherapy in first-line
treatment of non-small cell lung cancer with negative driver gene. The MOS in the
immunization combination group was significantly better than that in the chemotherapy group
(15.6 months vs. 10.9 months, HR 0.66), and the 1-year survival rate was 63% vs. 47%,
respectively. The ORR in the immunization combination group was also improved (38% vs. 25%),
and the MDOR was 11.3m vs. 5.6m, which was tolerable in terms of safety. The incidence of
grade 3-4 treatment-associated AE was 47% in the immune-combined group and 38% in the
chemotherapy group. From the perspective of mechanism, chemotherapy can enhance the
immunogenicity of tumor cells, damage the immune cell inhibitory activity, which can induce
tumor cell apoptosis, expression of MHC class 1 molecules increases and mature dendritic
cells to promote the immune response, in the design, add 2 cycles of chemotherapy short-term
intensive treatment, make up the immune short board, For example, the early onset of slow and
immune characteristic events such as large tumor load, pseudo progression, hyperrogression
and other problems, to achieve the optimization and upgrading of the scheme.
Based on Rationale 307, Tislelizumab was approved on January 12, 2021 for first-line
treatment in combination with paclitaxel and carboplatin in patients with locally advanced or
metastatic squamous non-small cell lung cancer. t the same time, Tislelizumab initial
efficacy in patients with extensive small-cell lung cancr.Rational-206 study is a phase Ⅱ
multi-cohort study of Tislelizumab combined with first-line platinum-containing chemotherapy
in patients with advanced lung cancer in China. The MPFS in the SCLC cohort was about 7
months, and the MOS reached 15.6 months.
Based on the above studies and data, in the second-line treatment of SCLC, anti-vascular
targeted drugs combined with chemotherapy can obtain a certain survival benefit, especially
for patients with sensitive recurrence, and the benefit is more significant. he immune
checkpoint inhibitors have gradually emerged in the second-line and later treatment of SCLC,
but the single drug effect has not been a great breakthrough; a small molecule antiangiogenic
targeted drug in China, Anlotinib has obtained third-line and later indications of SCLC
through ALTER1202 data, and has been included in the 2019 CSCO Guidelines for the Diagnosis
and Treatment of Primary Lung Cancer. t the same time, it is similar to the Checkmate9LA
study regimen, combined with two cycles of chemotherapy, to improve the short-term efficacy.
Therefore, Anlotinib combined with Tislelizumab, a PD-1 inhibitor, and 2 cycles of Irinotecan
monotherapy were tried in second-line SCLC, with the hope of breaking through the
difficulties of high recurrence rate and rapid disease progression of existing second-line
SCLC chemotherapy, regardless of platinum-sensitive recurrence or platinum-resistant
recurrence, and providing more options for SCLC patients.