Qilu Pharmaceutical's Iparomlimab and Tuvonralimab (QL1706) to Be Featured at ESMO 2023 with Promising Phase II Data in Recurrent or Metastatic Cervical Cancer

JinanOctober 18, 2023PR Newswire -- Clinical data of Qilu Pharmaceutical's innovative bifunctional combination antibody Aipaloli Tovorili Monoclonal Antibody (QL1706) will be presented as a brief oral report at the 2023 European Society for Medical Oncology (ESMO) Annual Meeting. The ESMO conference, the world’s top academic meeting in the field of medical oncology, will be held from October 20 to 24 in Madrid, Spain. The report will present the latest progress from a multicenter, single-arm Phase II clinical study on Aipaloli Tovorili Monoclonal Antibody combined with chemotherapy, with or without Bevacizumab, as first-line treatment for recurrent or metastatic cervical cancer.

In addition, a multicenter, randomized, double-blind, parallel-controlled Phase III clinical trial of Qilu Pharmaceutical's pertuzumab biosimilar (QL1209) in combination with trastuzumab and docetaxel as neoadjuvant treatment for early or locally advanced HER2-positive, hormone receptor-negative breast cancer will be presented as a poster at the ESMO conference.
1. Aipalolituo VorilizumabPhase II Clinical Study

Combination of immunotherapy and chemotherapy has become a first-line treatment strategy for recurrent/metastatic cervical cancer. Aipalolituo Volirumab, a Class 1 new drug developed by Qilu Pharmaceutical, is a bifunctional antibody that targets both PD-1 and CTLA-4, exerting synergistic anti-tumor effects. The Phase Ib clinical study of Aipalolituo Volirumab in treating advanced solid tumors confirmed its significant efficacy as monotherapy in advanced cervical cancer. In patients with advanced cervical cancer who had not received prior immunotherapy, the objective response rate (ORR) reached 28.3%.^[1]To further explore the efficacy of dual immunotherapy combined with chemotherapy in patients with recurrent/metastatic cervical cancer, Qilu Pharmaceutical Co., Ltd. has conducted a multicenter, single-arm Phase II clinical study of Aipalolizumab and Tovorolizumab combined with chemotherapy, with or without Bevacizumab, as first-line treatment for patients with recurrent or metastatic cervical cancer.

The study enrolled patients with recurrent or metastatic cervical cancer who had not received systemic treatment, and they were treated with either Aipalolituo Vorilizumab combined with chemotherapy (Cohort 1) or further combined with Bevacizumab (Cohort 2) until disease progression, intolerable toxicity, or withdrawal of informed consent by the patient. The primary endpoint of the study was safety, while secondary endpoints included Objective Response Rate (ORR), Duration of Response (DOR), Disease Control Rate (DCR), and Progression-Free Survival (PFS) assessed by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as well as Overall Survival (OS).

The results showed that, as of April 24, 2023, the median follow-up time was 14.0 months. A total of 58 patients underwent at least one post-baseline efficacy evaluation, with an ORR of 81.0% (95% CI, 68.6-90.1), including 8 patients who achieved complete response (CR) and 39 patients who achieved partial response (PR). The DCR was 98.3% (95% CI, 90.8-100.0). The median PFS reached 14.3 months (95% CI, 9.2 months-not evaluable), and the median OS was not reached. Therefore, Iparomlimab in combination with toripalimab plus chemotherapy with or without bevacizumab demonstrated significant efficacy in treating recurrent or metastatic cervical cancer. A phase III clinical study of iparomlimab combined with toripalimab plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer is currently ongoing.

QL1209 Phase III Clinical Study

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

The study enrolled patients with early or locally advanced HER2-positive, estrogen receptor (ER)-negative, and progesterone receptor (PR)-negative breast cancer, who were randomly assigned in a 1:1 ratio to the QL1209 experimental group or the reference drug control group. Both groups received neoadjuvant therapy with QL1209/reference drug + trastuzumab + docetaxel (THP) for four cycles, followed by pathological response evaluation post-surgery. Subsequently, both groups underwent adjuvant chemotherapy with fluorouracil + epirubicin + cyclophosphamide (FEC) for cycles 5-7, and QL1209 + trastuzumab for cycles 8-20. The primary endpoint of the study was the total pathological complete response rate (tpCR) assessed by an independent review committee.

The study enrolled a total of 517 patients, of which 516 received treatment. In terms of efficacy, the tpCR rates assessed by IRC in the experimental group and the control group were 42.7% and 45.2%, respectively. The ratio of tpCR rates between the two groups was 0.946 (90% CI: 0.80-1.11), with the 90% CI of the rate ratio falling within the equivalence margin (0.76-1.32). Regarding safety, the incidence of treatment-emergent adverse events (TEAEs) during the treatment period was 94.6% in the experimental group and 96.1% in the control group; the incidence of grade 3 or higher TEAEs was 31.9% and 34.7%, respectively; the incidence of treatment-related adverse events (TRAEs) was 77.4% and 78.0%. In terms of immunogenicity, the incidence of anti-drug antibodies (ADA) and neutralizing antibodies (NAb) in the experimental group and the control group was similar (2.3% and 3.1%; 0.8% and 0.8%), and ADA positivity had no impact on efficacy, pharmacokinetics, or safety. These results suggest that the clinical efficacy of the two groups is similar, with no significant differences in safety or immunogenicity. Therefore, QL1209 is considered a biosimilar of pertuzumab.

References:

[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.