ESMO Asia 2025 | Updated efficacy and biomarkers of QL1706, a PD-1/CTLA-4 dual blocker

QL1706, the drug is a dual inhibitor, which we call bifunctional inhibitor, inhibition of PD-L1 and CTLA-4. This drug is published, you know, the previous results were published in STTT, Signal Transduction and Targeted Therapy, in 2024, the early, maybe March or February. Yes. So what we’re doing now, what we submit abstract and doing, you know, the submission of this article is the updates of efficacy and the predictive biomarkers of the QL1706. Also, this article was published in Cell Report Medicine. I remember it’s November of this year, just a month ago. Yes. So this drug, the background we can see this drug is combined immune checkpoint inhibitors, PD-1 and CTLA-4. But it’s a difference from bispecific antibodies. It’s different from, we know, the camrelizumab or other like Opdivo plus Yervoy, the treatments. It is a bifunctional MAP pair product. What we know about MAP pair is like medical engineering techniques. It can, you know, put the anti-PD-1 and anti-CTLA-4 antibody in a two versus one with an untrusted CTLA-4 antibody half-life is smaller to reducing the immune-related adverse events. As we know that most of the AE, the very serious adverse events, when we combine PD-L1 and CTLA-4, is mainly due to the CTLA-4. If we reduce the CTLA-4’s half-life, it would be much, much less of the adverse events, especially for the immune-related adverse events. So when we do these products, when we do, you know, a MAP pair product, we can control the CTLA-4 antibodies, the proportion of the CTLA-4 antibody, and we can construct it to reduce its half-life, which ultimately leads to very less immune-related adverse events. This drug is conditionally approved by NMPA. NMPA is a Chinese FDA. So in our trial, we can see the results. QL1706, the phase one clinical trial, was performed in 2020, March to 2021, July. It’s also including two phases, phase one study and phase one B study. Phase one study is a dose escalation study. Phase 1b study is dose expansion study. In phase 1 study, the dose escalation stage, we enrolled about 132 patients who were screened, and 99 patients were enrolled. So in the phase 1B, we found that five milligrams per kilo cancer, including nasopharyngeal carcinoma, including cervical cancer, etc. The main contents of this article are the updates of the survival of all those of this trial. Totally about over 500 patients. It’s about 518 patients. So that’s the update’s efficacy I can show you now. I can read out to you is the objective response rates about 70%, including all those levels. The median duration of response is very long. It’s over one year. It’s 12 months, 12.4 months. The median PFS is short, is 1.5 months, which is the most important thing for QL1709, the monotherapy treatment. Nearly 14 to 50 patients, 50% of the patients progress early on, which is why we do need, when we conduct a phase two trial and phase three trial, we have to put QL1709 plus with chemotherapy or ADCs. The monotherapy has a very serious issue. That nearly half of the patients couldn’t benefit from early on. But when the patients, when they stay in the trial, do not progress from the first or second month of the treatments, they have a very long duration of the response. This is very astonishing. You can see although nearly 14% to 50% of the patients progress early on, it also has a very long median OS, which is for whole patients is over one year. It’s 14.6 months. For the immunotherapy-naive patients, the duration of the response is nearly 13 months. The median OS is over a year and a half. For those who have immunotherapy-experienced patients, the median duration of the response is about 10.4 months. It’s also very long. The median OS is about one year. It’s 11.5 months. So this is the updates of this trial. What is most importantly in this trial that’s accepted and published in Cell Report Medicine is because we have done a very sophisticated translational research. We have collected those patients, the samples of those patients, including non-small cell lung cancer, nasopharyngeal cancer, and cervical cancer, and we do the DNA sequencing and the RNA sequencing. So why do we do this translational research? We do the research because I have introduced previously that about 40% to 50% of the patients will progress early on. If we can predict the treatment upon a baseline, we can exclude those patients from the treatment, then we can significantly increase the benefit for these patients enrolled in this trial. We can avoid those patients who are not any, have any benefits from this therapy. So we do this translational research and the results are promising.

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