Qilu Pharmaceutical Announces Promising Clinical Data for QL1706 in Extensive-Stage Small Cell Lung Cancer and Advanced Hepatocellular Carcinoma at ASCO 2023

JinanMay 30, 2023PR Newswire -- Recently, the official website of the American Society of Clinical Oncology (ASCO) announced the abstracts selected for the ASCO 2023 Annual Meeting. Qilu Pharmaceutical's immunotherapy combination antibody QL1706 (Iparomlimab/Tuvonralimab) has four clinical research abstracts selected, two of which are the latest clinical research progress of QL1706 in extensive-stage small cell lung cancer and advanced liver cancer.

Study 1: A Single-Arm, Multi-Center Phase II Clinical Study of QL1706 in Combination with Carboplatin and Etoposide as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer

This study is an open-label, single-arm, multi-center Phase II clinical trial aimed at evaluating the safety and efficacy of QL1706 in combination with carboplatin and etoposide as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). A total of 40 patients were enrolled in the study, with a median age of 58.5 years (range, 38-73). 87.5% of the patients were male, 80% had a history of smoking, and 90% had an ECOG performance status of 1.

As of the data cutoff date (January 16, 2023), the median treatment duration of QL1706 was 5.9 months (range, 0.7-8.9). All patients experienced at least one treatment-emergent adverse event (TEAE). A total of 32 patients (80%) experienced at least one treatment-related adverse event (TRAE) associated with QL1706. Fifteen patients (37.5%) experienced grade 3 to 4 TRAEs, with no grade 5 TRAEs reported and no adverse events leading to treatment discontinuation.

A total of 39 patients underwent at least one post-baseline tumor assessment, with 37 achieving partial response (PR) (including 2 unconfirmed PRs) and 1 showing stable disease (SD). According to RECIST criteria, the confirmed objective response rate (ORR) was 89.7% (35/39), and the disease control rate (DCR) was 97.4% (38/39). The median duration of response (mDoR) was 4.5 months, and the median progression-free survival (mPFS) was 5.7 months. The follow-up time for overall survival (OS) was 6.2 months, with the median OS not yet reached.

The results showed that QL1706 combined with carboplatin and etoposide was well-tolerated and demonstrated promising efficacy as a first-line treatment for extensive-stage small cell lung cancer.

Study Two: A Phase Ib/II Clinical Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of QL1706 or QL1604 Injection Combined with Bevacizumab Injection in Patients with Advanced Hepatocellular Carcinoma

QL1604 is a PD-1 monoclonal antibody. The molecular sequence, host cell, construct, transfection, and monoclonal selection process of the PD-1 monoclonal antibody component in QL1706 are identical to those of QL1604. In other words, QL1706 is developed by further transfecting an anti-CTLA-4 antibody recombinant plasmid into the QL1604 monoclonal cell line, followed by screening to ultimately obtain the QL1706 monoclonal cell strain. A preliminary factorial analysis experiment comparing the two has been conducted in preclinical studies.

This study is a multicenter, open-label, Phase Ib/II clinical trial, divided into three parts. The first part consists of a safety lead-in phase and an expansion phase. In the second part, patients are randomized to receive QL1604 or QL1706 (5mg/kg, Q3W) in combination with bevacizumab. In the third part, patients receive QL1706 (7.5mg/kg, Q3W) in combination with bevacizumab. The initiation of the third part is determined based on the results of the factorial analysis from the first and second parts. The primary endpoint is safety, and secondary endpoints include objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), etc.

As of the data cutoff date (November 18, 2022), a total of 76 patients were enrolled in Part 1 and Part 2 of the study (50 in the QL1706 group and 26 in the QL1604 group). Baseline characteristics were balanced between the two groups. The incidence of treatment-related adverse events (TRAEs) was 86% in the QL1706 group and 88.5% in the QL1604 group. The most common TRAEs in both groups were proteinuria (32.0% vs 30.8%), followed by decreased platelet count (26.0% vs 23.1%) and increased aspartate aminotransferase (22% vs 19.2%). The incidence of treatment-related serious adverse events was 16% and 23.1%, respectively. The incidence of immune-related adverse events was 50% and 19.2%, respectively.

In the evaluable population for efficacy, the ORR for the QL1706 group and QL1604 group was 38.3% (18/47) and 15.4% (4/26), respectively, while the DCR was 74.5% and 69.2%, respectively. The median progression-free survival (mPFS) for the QL1706 group and QL1604 group was 6.7 months and 5.4 months, respectively. The median overall survival has not yet been reached.

The results showed that, compared with PD-1 monoclonal antibody combined with bevacizumab, QL1706 combined with bevacizumab demonstrated a higher ORR and longer PFS as first-line treatment for advanced hepatocellular carcinoma. The findings of this study support further phase III clinical research on QL1706 combined with bevacizumab as first-line treatment for advanced hepatocellular carcinoma.。