1997P - A study of sintilimab combined with anlotinib and chemotherapy as second-line or later therapy in extensive-disease small cell lung cancer

Background

SCLC is characterized by rapid growth, drug resistance, and early metastasis. At present, etoposide combined with platinum is the standard first-line treatment for ED-SCLC, and the second-line and later treatment options are limited. This study investigated the efficacy and safety of sintilimab combined with anlotinib and albumin-bound paclitaxel in the treatment of ED-SCLC.

Methods

This is a single-arm, phase II study (ChiCTR2100049390). Patients with ED-SCLC were enrolled after screening and meeting the inclusion and exclusion criteria. Patients were treated with sintilimab (200mg, d1, Q3W) combined with anlotinib (12mg, d1-d14, Q3W) and albumin-paclitaxel (100mg, d1-d8, Q3W). The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Results

From July 2021 to February 2023, a total of 30 subjects were enrolled, of which 25 patients could be evaluated. The median age was 59 years, including 20 males, 21 patients with ECOG 1, 12 patients with smoking history, and 10 patients with brain metastases at baseline. All cases were in stage IV. As of April 28, 2023, the median follow-up was 12.5 months. The ORR was 64%, including 16 cases of PR, 4 cases of SD, and 5 cases of PD. The DCR was 80%. The mDOR was 6.64 (5.32,10.5), and the mTTR was 1.5 months. The mPFS was .91 (4.86,6.8), 6-month and 12-month PFS rates were 49% and 9.8%, respectively. The median OS was 13.2 (9.69, NA), and the 12- and 24-month PFS rates were 60.9% and 25.2%, respectively. The TRAE was 84% (21 cases), of which ≥3 grade TRAE was 20%, including aspartate aminotransferase increased, alanine aminotransferase increased, rash, neutropenia, and lymphopenia. A total of 9 (36%) subjects had immune-related adverse reactions (irAE). ≥3 grade irAE included spartate aminotransferase increased, alanine aminotransferase increased, rash. No AE leading to death occurred.

Conclusions

Sintilimab combined with anlotinib and albumin-paclitaxel demonstrated significant clinical activity and a manageable safety profile for patients with ED-SCLC. The long-term efficacy is still under follow-up.

Clinical trial identification

ChiCTR2100049390.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Innovent Biologics, Inc.

Disclosure

All authors have declared no conflicts of interest.