ESMO Asia 2025 | Phase I trial of BPB-101, a GARP/TGF-β/PD-L1 bispecific ADC in solid tumors

APG2449 is a second generation of ALK and ROS1 and also FAK inhibitors. We like to call it dirty compounds because it’s not selective inhibitors. You have a very wide range of the inhibition of those tyrosine kinases. So this drug, we have to report this phase one trial in e-clinical medicine this year in October. So the magazine is based on one of the Lancet population groups. So this drug, we have performed this phase one clinical trials, including dose escalation and dose expansion studies, which the main purpose of this, the main objective of this phase one trial is to determine the MTD and RP2D in the first stage, which is the escalation stage of this phase one trial. And also when we acquire our objective, we start to expand in RP2D for those expansions, which is the second stage of this phase one trial. So, totally we have 200 patients screened for eligibility, and finally we have 144 patients enrolled. That is 88 patients in dose escalation stage and 56 patients in dose expansion stage. All the patients will receive APG2449. And in dose expansion, we have found RP2D is 1,200 milligrams. So all the patients, we divide them into three parts. One part is the solid tumor, advanced solid tumor. When we do the dose escalation, we include not only non-muscular cancer, non-small cell lung cancer, but also other cancers that are more often ALK or ROS1 positive. We divided them into four groups, which is ALK naïve, just have not received any prior TK treatments, and the ALK TK failed patients, and also the ROS1 TK naïve and the ROS1-failed patients. So when we divided them into groups, we can see the very promising results for the patients. The results show the efficacy for ALK-naive population. The objective response rates were nearly 80%, which is very high. And for those which we most focus on, the patients have already failed on second-generation TKIs. The objective response rate is 20%. That’s when we look at the patients receiving high dose levels, the objective response rate has raised to nearly about 50%. So this is why this drug could be promising and be accepted by the population group of Lancet. So this is the main reason, because you have a very promising effect of those who have failed on second-generation population, which leads to the most important questions of the PD study. So when we look into these patients, we realize that the phosphorylation of FAK is a very important mechanism of drug resistance, which is very important. But because APG2449 is not only an ALK and the ROS1 inhibitor, it also inhibits the phosphorylation of FAK. I don’t know if you recall this year, early in this year, there is a clinical trial for the patients with KRAS-G12C, the patients, using KRAS-G12C inhibitors, and the plus, the combination of another drug, which is the inhibitor of phosphorylation or FAK, which have a very promising OR. All the patients have objective response. This is very promising. So if we, just similar to KRAS-G12C, for the patients with ALK positive and ROS1 positive for them have failed on second generation of TKI. A lot of the patients were because the acquired resistance of FAK phosphorylation. So for this drug, it has the inhibition ability to phosphorylate FAK. So when we do the PD analysis, we found that the patients have baseline phosphorylated FAK, the expression is high, have a very, very promising, very good efficacy, have nearly 70%. So this is the main reason that this drug has the, you know, worth of further developments.

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