NCT05027100

One Arm, Exploratory Study of Tislelizumab Combined With Anlotinib and 2-cycle Irinotecan Monotherapy as Second Treatment of Small Cell Lung Cancer

Status unknown NA Last updated 30 June 2022

What this trial tests

NA trial testing Anlotinib Tislelizumab Irinotecan in Small Cell Lung Cancer (SCLC) in 33 participants. Status unknown.

Timeline

30 September 2021

Primary endpoint
1 December 2022

1 June 2023

Quick facts

Lead sponsor	Haibo Zhang
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	33
Start date	30 September 2021
Primary completion	1 December 2022
Estimated completion	1 June 2023
Sites	1 location across China

Drugs / interventions tested

• Anlotinib Tislelizumab Irinotecan — full drug profile →

Conditions studied

• Small Cell Lung Cancer (SCLC) — all drugs for Small Cell Lung Cancer (SCLC) →

Sponsor

Haibo Zhang — full company profile →

Who can join

Adults 18 to 75, any sex, with Small Cell Lung Cancer (SCLC). Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• ORR(Investigator-assessed)
  Time frame: up to 48months
  Tumor remission is revaluted by investigator according to RECIST v 1.1

Sponsor's own description

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 be

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
   Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
2. Treatment patterns and outcomes of immunotherapy in extensive-stage small-cell lung cancer based on real-world practice.
   Yang Y, Ai X, Xu H, Yang G, et al · · 2022 · cited 16× · PMID 36218023 · DOI 10.1111/1759-7714.14684
3. Targeted Therapies in Small Cell Lung Cancer: From Old Failures to Novel Therapeutic Strategies.
   Cani M, Napoli VM, Garbo E, Ferrari G, et al · · 2023 · cited 11× · PMID 37240229 · DOI 10.3390/ijms24108883
4. Efficacy and safety of tislelizumab plus anlotinib and irinotecan as second-line treatment for extensive-stage small cell lung cancer: a single-arm, open-label, phase II trial.
   Chen X, Wang J, Liu L, Chai X, et al · · 2025 · PMID 41181839 · DOI 10.1016/j.eclinm.2025.103502