Qilu Pharmaceutical Submits NDA for QL1706, the World’s First PD-1/CTLA-4 Bispecific Combination Antibody

On August 12, the CDE website showed that the marketing application of Qilu Pharmaceutical's Aipaloli Monoclonal Antibody/Tuvorali Monoclonal Antibody (QL1706) Injection was accepted. This is the world’s first PD-1/CTLA-4 combination antibody to be submitted for marketing.

QL1706 is a bifunctional combination antibody developed by Qilu Pharmaceutical, utilizing the MabPair technology platform to simultaneously produce two engineered monoclonal antibodies in a single cell at a ratio of approximately 2:1 — the programmed death receptor 1 (PD-1) IgG4 antibody Iparomlimab and the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) IgG1 antibody Tuvonralimab.

Therefore, QL1706 can simultaneously inhibit PD-1 and CTLA-4, and the CTLA-4 antibody component has a shorter clearance half-life in vivo, resulting in a shorter exposure time of the CTLA-4 antibody within a dosing cycle. Thus, QL1706 has the synergistic mechanism of action of blocking both PD-1 and CTLA-4 while reducing the toxicity generated by the CTLA-4 antibody.

On May 8 this year, the Phase I clinical results of QL1706 in the treatment of advanced solid tumors were published in the authoritative international oncology journal, *Journal of Hematology & Oncology*. The study showed that QL1706 has good safety and tolerability, with a favorable objective response rate in patients with advanced solid tumors, and demonstrates higher anti-tumor activity in nasopharyngeal cancer, cervical cancer, and lung cancer.

Currently, QL1706 has launched several Phase III clinical trials, including first-line treatment for cervical cancer, adjuvant treatment for non-small cell lung cancer, first-line treatment for advanced non-small cell lung cancer, and first-line treatment for nasopharyngeal carcinoma.

On June 7 this year, two Phase III studies (DUBHE-L-304 and DUBHE-L-303) of Qilu Pharmaceutical's QL1706 for non-small cell lung cancer were presented at the 2023 ASCO Annual Meeting.

DUBHE-L-304 Study (NCT05487391) is a double-blind, randomized, placebo-controlled Phase III clinical trial. The study plans to enroll 632 patients with completely surgically resected stage II-IIIB non-small cell lung cancer (NSCLC), who do not have EGFR-sensitive mutations or ALK fusion genes. Patients will receive either QL1706 or placebo treatment for 16 cycles, along with adjuvant chemotherapy for 2-4 cycles. The primary endpoints are investigator-assessed disease-free survival (DFS) in the PD-L1≥1% population and investigator-assessed DFS in the overall population. The first patient was enrolled on December 8, 2022.

DUBHE-L-303 Study (NCT05690945) is a double-blind, randomized, active-controlled Phase III trial. The study plans to enroll 650 patients with PD-L1 negative, EGFR/ALK mutation-free stage IIIB-IV NSCLC, who will receive four cycles of either QL1706 or tislelizumab in combination with chemotherapy, followed by maintenance therapy with QL1706 or tislelizumab (for non-squamous cell carcinoma, maintenance therapy with QL1706 or tislelizumab plus pemetrexed will be administered). The primary endpoints are investigator-assessed progression-free survival (PFS) (RECIST 1.1) and overall survival (OS). The first patient was treated on February 16, 2023.

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