Qilu Pharmaceutical Announces Progress of Clinical Study of QL1706, an Innovative Bifunctional Antibody

JINAN,China,Dec. 29,2022 -- In 2022,Qilu Pharmaceutical revealed the latest progress being made with several clinical studies involving its innovative bifunctional antibody,QL1706,at several international and Chinese academic conferences,including the American Association for Cancer Research (AACR) 2022 Annual Meeting,the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting,the Chinese Society of Clinical Oncology (CSCO) 2022 Annual Meeting,and the European Society for Medical Oncology (ESMO) 2022 Asia Congress.

Antibodies targeting programmed death receptor 1 and its ligand (PD-1/PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have been widely used in clinical practices to treat a variety of advanced tumors. However,some combinations of dual immune checkpoint inhibitors (ICIs) limit the maximum clinical benefits for patients due to greater toxicity. QL1706 is an innovative combination of anti-PD-1 monoclonal antibody and anti-CTLA-4 monoclonal antibody,developed on the MabPair technology platform. QL1706 has significant advantages in terms of proportional allocation between CTLA-4 IgG1 and PD-1 IgG4 antibodies and flexibility in the selection of the Fc backbone. QL1706 introduces mutations onto the heavy chain of CTLA-4 antibodies,so CTLA-4 IgG1 has a shorter elimination half-life than PD-1 IgG4 (4-5 days and 6-9 days,respectively),resulting in shorter patient exposure to CTLA-4 antibodies. QL1706 bifunctional antibody combines the activity of both PD-1 and CTLA-4 antibodies,while helping to attenuate the toxicity caused by CTLA-4 antibodies.

At AACR's annual meetings in 2021 and 2022,Qilu Pharmaceutical reported the results of the Phase Ia/Ib studies of QL1706 for advanced solid tumors in a poster presentation (abstract numbers: CT119,CT520). In the phase Ia study,a dose of 0.3-10.0 mg/kg (intravenous,every 3 weeks for a cycle) was used in a 3+3 dose escalation study; and 5.0 mg/kg and 7.5 mg/kg were used as extension doses. In the QL1706 10 mg/kg dose group,two cases of dose-limiting toxicity (DLT) occurred,including one case of grade-3 thrombocytopenia with grade-1 gingival bleeding and one case of grade-4 immunomodulatory nephritis,based on which the final recommended dose (RP2D) in phase 2 was determined to be 5 mg/kg. As of September 30,2021,among a total of 518 patients enrolled in phaseIa and Ib,the incidence of treatment-related adverse events (TRAEs) was 72.2%,and the incidence of grade-3 TRAEs or above was 13.5%. The most common TRAEs with an incidence greater than 10% were rashes (17.6%),pruritus (12.5%),and hypothyroidism (11.6%).

At the ASCO 2022 Meeting,Qilu Pharmaceutical announced the results of the study of QL1706 for the treatment of patients with advanced nasopharyngeal cancer (abstract no. 6034) and cervical cancer (abstract no. 5535) in a poster presentation. As of the data cut-off date,110 patients with nasopharyngeal cancer were enrolled in Phase Ia/Ib studies,of whom 71.8% had received second-line therapy or above,and 43.6% immunotherapy. Objective response was achieved in 24.5% of the patients,with a confirmed ORR of 39.1% (9/23) and 38.5% (15/39) among patients who had received first- and second-line therapies or above without immunotherapy,respectively. After a median follow-up of 7.7 months,the median progression-free survival (PFS) was 2.0 months (95% CI 1.4-2.9),the 6-month PFS rate was 47.4% while median overall survival (OS) data was not yet available.

In the phase Ib study,53 patients with cervical cancer were enrolled,83% of whom had squamous carcinoma and 17% adenocarcinoma; and 62% and 38% had received first- and second-line (or above) treatment,respectively. As of the data cut-off date,34.0% of the patients were still receiving QL1706 treatment,and 60.3% had witnessed reduction in target lesions. One (2%) patient achieved complete response(CR) and 14 (26%) partial response(PR),with a confirmed ORR of 28% and a disease control rate of 55%. The median follow-up was 5.6 months,with a median PFS of 4.2 months and a 6-month PFS rate of 37%. Median OS was not achieved.

At the CSCO 2022 meeting,Qilu Pharmaceutical announced in a poster presentation the results of the phase II clinical study of QL1706 in combination with chemotherapy with or without bevacizumab in first-line treatment of recurrent or metastatic cervical cancer (paper number: 12865). Among the 57 patients with recurrent or metastatic cervical cancer enrolled,30 were treated with QL1706 in combination with chemotherapy and QL1706 in combination with chemotherapy plus bevacizumab,with an overall ORR of 77.2% and DCR of 98.2%. Among them,the ORR and DCR of the group treated with QL1706 in combination with chemotherapy were 74.1% and 100.0%,respectively; and QL1706 in combination with chemotherapy plus bevacizumab 80.0% and 96.7%,median PFS and median OS were not achieved. Based on the results of this study,a phase III clinical study (NCT05446883) designed to evaluate the efficacy and safety of QL1706 in combination with paclitaxel-cisplatin/carboplatin with or without bevacizumab in the first-line treatment of recurrent or metastatic cervical cancer has now been conducted.

At the recent ESMO Asia Congresss,Qilu Pharmaceutical announced in a poster presentation the results of the Phase II clinical study of QL1706 in combination with chemotherapy with or without bevacizumab for the treatment of patients with advanced EGFR wild-type and EGFR mutant non-small cell lung cancer (abstract numbers: 622 and 637).

As various studies on QL1706 progress,its clinical layout have been covered for several major disease areas including lung cancer,gastrointestinal tumors,gynecological tumors,head and neck tumors and urological tumors. In addition to first-line treatment for cervical cancer,QL1706 will also be researched in more phase III clinical studies on first-line treatment and adjuvant therapy for non-small cell lung cancer and liver cancer,which is expected to create a new landscape of immunotherapy,providing more treatment options for patients and more possibilities for unmet clinical needs.

References：

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2. Li Zhang,Hongyun Zhao,Yuxiang Ma,et al. Development and preliminary clinical activity of QL1706 (PSB205),a combination of anti-PD1 and anti-CTLA-4 antibodies manufactured together as a single product [abstract]. American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT119.

3. Li Zhang,Yan Huang,et al. The safety summary of the phase 1a/b trial of QL1706,a novel dual immune checkpoint blockade containing a mixture of anti-PD1 IgG4 and anti-CTLA4 IgG1 antibodies,for advanced malignant tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT520.

4. Hongyun Zhao,Wenfeng Fang,et al. Efficacy and safety of QL1706,for advanced nasopharyngeal carcinoma (NPC): Pooled cohort data from phase 1a/1b trials. J Clin Oncol 40,2022 (suppl 16; abstr 6034)

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