JINAN, China, Oct. 19, 2023 /PRNewswire/ -- Data from Qilu Pharmaceutical's clinical trial of its novel bifunctional antibody, QL1706 (iparomlimab and tuvonralimab), will be unveiled during a mini oral presentation at the European Society for Medical Oncology (ESMO) Annual Congress 2023. The ESMO Congress, the premier global conference in the field of medical oncology, will take place in Madrid, Spain from October 20 to 24, 2023.

中国济南，2023年10月19日/PRNewswire/-来自齐鲁制药公司新型双功能抗体QL1706（iparomlimab和tuvonralimab）临床试验的数据将在欧洲肿瘤内科学会（ESMO）的小型口头报告中公布。）2023年会。ESMO大会是医学肿瘤学领域的首要全球会议，将于2023年10月20日至24日在西班牙马德里举行。

The presentation will provide updates on a multicenter, single-arm phase II clinical trial of QL1706. This innovative treatment, used in combination with chemotherapy and with or without bevacizumab, is being investigated for its potential as a first-line therapy for recurrent or metastatic cervical cancer (CC)..

该演示文稿将提供QL1706多中心，单臂II期临床试验的最新信息。正在研究这种与化疗联合使用或不使用贝伐单抗的创新疗法作为复发性或转移性宫颈癌（CC）一线治疗的潜力。。

Additionally, a poster showcasing a multicenter, randomized, double-blind, parallel-controlled Phase III clinical trial conducted by Qilu Pharmaceutical. This study examines the use of a combination of pertuzumab biosimilar (QL1209), trastuzumab and docetaxel as a neoadjuvant therapy for the treatment of early or locally advanced HER2-positive, hormone receptor-negative breast cancer will be featured at the congress..

此外，还有一张海报展示了齐鲁制药进行的多中心，随机，双盲，平行对照的III期临床试验。本研究探讨了哌曲单抗生物仿制药（QL1209）、曲妥珠单抗和多西他赛联合治疗早期或局部晚期HER2阳性、激素受体阴性乳腺癌的新辅助治疗方法。。

I. Phase II Clinical Trial of QL1706

一、 QL1706的II期临床试验

Combination immunotherapy has emerged as the first-line treatment approach for recurrent/metastatic CC. Qilu Pharmaceutical's class 1 novel drug, QL1706, is a bifunctional antibody that simultaneously targets PD-1 and CTLA-4, producing synergistic anti-tumor effects. The phase Ib clinical trial of QL1706 for advanced solid tumors has confirmed the drug's promising efficacy of monotherapy in patients with advanced cervical cancer (ACC).

联合免疫治疗已成为复发/转移性CC的一线治疗方法。齐鲁制药的1类新药QL1706是一种双功能抗体，可同时靶向PD-1和CTLA-4，产生协同抗肿瘤作用。QL1706用于晚期实体瘤的Ib期临床试验证实了该药物在晚期宫颈癌（ACC）患者中的单一疗法的有希望的功效。

An objective response rate (ORR) of 28.3% was observed in ACC patients who had not previously undergone immunotherapy[1] . To further investigate the efficacy of dual immunotherapy combined with chemotherapy in patients with recurrent/metastatic CC, a multicenter, single-arm phase II clinical trial was initiated to assess QL1706, administered with chemotherapy and with or without bevacizumab, as a first-line treatment for recurrent or metastatic CC..

在未接受过免疫治疗的ACC患者中观察到客观缓解率（ORR）为28.3%[1]。为了进一步研究双重免疫治疗联合化疗对复发/转移性CC患者的疗效，开展了一项多中心，单臂II期临床试验，以评估QL1706，联合化疗和联合或不联合贝伐单抗作为一线治疗复发或转移性CC。。

The study enrolled recurrent or metastatic CC patients who had not undergone systemic therapy. These patients were treated with either QL1706-chemotherapy (Cohort 1) or QL1706-chemotherapy-bevacizumab (Cohort 2) until disease progression, the occurrence of intolerable toxicity or the patient's withdrawal of informed consent.

该研究纳入了未接受全身治疗的复发或转移性CC患者。这些患者接受QL1706化疗（队列1）或QL1706化疗-贝伐单抗（队列2）治疗，直至疾病进展，出现无法忍受的毒性或患者撤回知情同意书。

The primary endpoint of the study was safety, with secondary endpoints including ORR, duration of response (DOR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS), which were assessed by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)..

该研究的主要终点是安全性，次要终点包括ORR，反应持续时间（DOR），疾病控制率（DCR），无进展生存期（PFS）和总生存期（OS），由研究者根据实体瘤的反应评估标准（RECIST 1.1）。。

The findings of this study indicated that as of April 24, 2023, out of 58 patients who received at least one post-baseline efficacy evaluation, ORR was 81.0% (95% CI, 68.6-90.1). The results were observed over a median follow-up duration of 14.0 months. Among these patients, eight achieved complete response (CR) and 39 achieved partial response (PR).

这项研究的结果表明，截至2023年4月24日，在接受至少一项基线后疗效评估的58名患者中，ORR为81.0%（95%CI，68.6-90.1）。结果在中位数随访14.0个月。在这些患者中，8例获得完全缓解（CR），39例获得部分缓解（PR）。

The DCR was 98.3% (95% CI, 90.8-100.0). The median PFS reached 14.3 months (95% CI, 9.2 months to not estimable), while the median OS has not yet been reached. The data demonstrate the outstanding efficacy of a combination of QL1706 and chemotherapy, with or without bevacizumab, for treating recurrent or metastatic CC.

DCR为98.3%（95%CI，90.8-100.0）。中位PFS达到14.3个月（95%CI，9.2个月不可估计），而中位OS​​尚未达到。数据表明QL1706和化疗联合或不联合贝伐单抗治疗复发或转移性CC的优异疗效。

A Phase III clinical trial of the combination therapy is currently ongoing..

目前正在进行联合治疗的III期临床试验。。

Phase III Clinical Trial of QL1209

QL1209的III期临床试验

A multicenter, randomized, double-blind, parallel-controlled Phase III clinical trial was conducted to assess the clinical equivalence of QL1209 and the original drug, both used in conjunction with trastuzumab and docetaxel as a neoadjuvant treatment for early or locally advanced HER2-positive, hormone receptor-negative breast cancer..

进行多中心，随机，双盲，平行对照III期临床试验以评估QL1209与原始药物的临床等效性，两者均与曲妥珠单抗和多西紫杉醇联合用作早期或局部晚期HER2阳性的新辅助治疗，激素受体阴性乳腺癌。。

The study enrolled patients with early or locally advanced HER2-positive, estrogen receptor (ER) and progesterone receptor (PR) negative breast cancer. These patients were randomly assigned in a 1:1 ratio to either the QL1209 trial group or the control group receiving the original drug. Both groups underwent four cycles of neoadjuvant therapy with QL1209/original drug + trastuzumab + docetaxel (THP), followed by a post-surgical pathological response evaluation.

该研究纳入了早期或局部晚期HER2阳性，雌激素受体（ER）和孕激素受体（PR）阴性乳腺癌患者。这些患者以1:1的比例随机分配到QL1209试验组或接受原始药物的对照组。两组均接受QL1209/原始药物+曲妥珠单抗+多西紫杉醇（THP）的四个周期的新辅助治疗，然后进行手术后病理反应评估。

Both groups then received adjuvant chemotherapy with fluorouracil-epirubicin-cyclophosphamide (FEC) for cycles 5-7, and QL1209 + trastuzumab for cycles 8-20. The study's primary endpoint was the total pathological complete response (tpCR), as assessed by an independent review committee (IRC)..

然后两组均接受氟尿嘧啶-表柔比星-环磷酰胺（FEC）辅助化疗5-7周期，QL1209+曲妥珠单抗治疗8-20周期。该研究的主要终点是由独立审查委员会（IRC）评估的总病理完全缓解（tpCR）。。

The study enrolled 517 patients, of which 516 received treatment. In terms of efficacy, the IRC-assessed tpCR rates were 42.7% in the trial group, and 45.2% in the control group. The ratio of the tpCR rate between the two groups was 0.946 (90% CI: 0.80-1.11), falling within the equivalence margin (0.76-1.32).

该研究招募了517名患者，其中516名接受了治疗。在疗效方面，IRC评估的tpCR率在试验组为42.7%，对照组为45.2%。两组之间tpCR率的比率为0.946（90%CI:0.80-1.11），落在等效范围内（0.76-1.32）。

Regarding safety, the incidence of treatment-emergent adverse events (TEAEs) was 94.6% in the trial group and 96.1% in the control group; the occurrence of grade 3 or higher TEAEs was 31.9% in the former group and 34.7% in the latter while the incidence of treatment-related adverse events (TRAEs) was 77.4% and 78.0%, respectively.

在安全性方面，试验组治疗出现不良事件（TEAE）的发生率为94.6%，对照组为96.1%；3级或更高TEAE的发生率前者为31.9%，后者为34.7%，而治疗相关不良事件（TRAEs）的发生率分别为77.4%和78.0%。

As for immunogenicity, the incidence of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) was similar between the two groups (2.3% and 3.1%; 0.8% and 0.8%, respectively). ADA positivity had no impact on efficacy, pharmacokinetics or safety. These findings suggest that the two groups exhibit similar clinical efficacy, with no significant differences observed in safety or immunogenicity. Based on these results, it can be concluded that QL1209 is a biosimilar to pertuzumab..

至于免疫原性，两组之间抗药物抗体（ADAs）和中和抗体（NAbs）的发生率相似（分别为2.3%和3.1%；0.8%和0.8%）。ADA阳性对疗效，药代动力学或安全性没有影响。这些发现表明两组表现出相似的临床疗效，在安全性或免疫原性方面没有观察到显着差异。基于这些结果，可以得出结论，QL1209是帕妥珠单抗的生物仿制药。。

References:

参考文献：

1.    Zhao Y, et al. First-in-human phase I/Ib study of QL1706 (PSB205), a bifunctional PD1/CTLA4 dual blocker, in patients with advanced solid tumors. J Hematol Oncol. 2023 May 8;16(1):50. doi: 10.1186/s13045-023-01445-1.

1.Zhao Y，et al。首次在人类I/Ib期研究QL1706（PSB205），一种双功能PD1/CTLA4双阻断剂，用于晚期实体瘤患者。J Hematol Oncol。2023年5月8日；16（1）：50。doi:10.1186/s13045-023-01445-1。

SOURCE Qilu Pharmaceutical Co., Ltd.

来源齐鲁制药有限公司。