SCLC: Yilian Bio Shows Strong Potential, Merck & Co. Holds a Stronger Hand
MediLink
Antibody-Drug Conjugates Developer
GSK
Pharmaceutical R&D Manufacturer
Daiichi - Sankyo
Pharmaceutical Development, Production, Sales, and Consulting Service Provider
In the field of small cell lung cancer,AmgenTheDLL3/CD3The bispecific antibody has been approved for marketing,开创了实体瘤TCEA New Chapter in Treatment, and inADCField, with the development of related target drugs in recent years,SCLCThe competition in clinical layout is also quite fierce. Recently, MediLinkESMOThe meeting announced its targetedB7-H3-ADC
YL201Clinical data, and inSCLCIndications:ORRArrived61%，mPFSFor6.2Months, using the same Daiichi - Sankyo andGSKTwo products targeting the same targetADCIn comparison, the efficacy is equally matched.
According to the disclosure by MediLink, the dose escalation for YL201 ranged from 0.8mg/kg to 3.0mg/kg. However, DLTs were observed at doses of 2.8mg/kg and 3.0mg/kg. Therefore, subsequent expansion studies selected doses of 2.0mg/kg and 2.4mg/kg, enrolling a total of 263 patients, including 67 patients with SCLC who had received two or more prior lines of treatment.
In terms of efficacy, inIn all patients, the ORR was 68.1%, and the mPFS was 6.2 months, with an ORR of 70.0% and an mPFS of 6.2 months at doses ≥2.0 mg/kg. Additionally, in patients with brain metastases, the overall ORR was 52.2%, and the mPFS was 5.3 months.。
Next, let's look at the Phase I clinical dose-expansion cohort data of HS-20093 released by GSK and Hansoh at the WCLC. A total of 56 patients with ES-SCLC were enrolled. All patients had received platinum plus etoposide treatment, 73.2% of the patients had received immunotherapy, and 23.2% had received TOPO1 inhibitors. The expansion doses were also divided into two groups: 8 mg/kg and 10 mg/kg.
In terms of efficacy, the ORR was 61.3%, DCR was 80.6%, mDOR was 6.4 months, mPFS was 5.9 months, and mOS was 9.8 months in the 8.0 mg/kg dose group; while in the 10.0 mg/kg dose group, the ORR was 50.0%, DCR was 95.5%, mDOR was 8.9 months, mPFS was 7.3 months, and mOS has not yet been reached. Comparing the two groups, the lower dose showed a relatively higher ORR, which has also been observed with other ADC drugs—increasing the dose may lead to a decrease in overall response rate, and mPFS might also decline, potentially due to toxic side effects associated with higher doses. This further demonstrates the complexity of ADC drugs.
Let's take a look at the data from Daiichi-Sankyo, the leading ADC company, presented at the WCLC conference. The Phase II IDeate-Lung01 study of DS-7300 for the treatment of ES-SCLC also utilized two dose groups: 8 mg/kg and 12 mg/kg.
In terms of effectiveness, in88In the case of tumor evaluation patients,8 mg/kgDose GroupORRFor26.1%、DCRFor80.4%、mDORFor7.9Months,mPFSFor4.2Months,mOSFor9.4Months,12 mg/kgDose GroupORRFor54.8%、DCRFor90.5%、mDORFor4.2Months,mPFSFor5.5Months,mOSFor11.8Months；
In the subgroup of patients with brain metastases, the response rates for the 8 mg/kg and 12 mg/kg dose groups were 66.7% and 50.0%, respectively. Additionally, two patients in each group achieved CR.
Finally, let's compare Amgen's marketed TCE bispecific antibody AMG757. Last year, Amgen published the Phase II clinical results of this therapy in the top international journal NEJM, showing a further increase in ORR, reaching up to 40% in the 10mg dose group. A total of 220 patients received treatment with the bispecific antibody AMG757 in the clinical trial. The median number of prior treatment lines for the patients was 2. Among the treated and evaluated patients,The median follow-up time was 10.6 months in the 10 mg group and 10.3 months in the 100 mg group. Objective response rates were 40% (97.5% CI, 29–52) in the 10 mg group and 32% (97.5% CI, 21–44) in the 100 mg group.Among these patients who achieved objective remission, 59% (40 out of 68 patients) had a duration of remission lasting at least 6 months. At the time of data cutoff, 22 out of 40 patients (55%) in the 10 mg group and 16 out of 28 patients (57%) in the 100 mg group still maintained objective remission.The median progression-free survival was 4.9 months (95% CI, 2.9–6.7) in the 10 mg group and 3.9 months (95% CI, 2.6–4.4) in the 100 mg group. The estimated 9-month overall survival rates were 68% and 66%, respectively.。
Overall, the three B7-H3 ADC drugs have achieved remarkable efficacy in SCLC, and in terms of efficacy, all three drugs surpass the already marketed DLL3/CD3 bispecific antibody. However, discussing efficacy without considering the patient baseline is also misleading. After the subsequent detailed data disclosure, ADC and TCE can be compared in parallel.
In addition, forDLL3 TCE Therapy and B7-H3 ADC Therapy, Two therapies fromThere are also essential differences in technology, and the targets are different, so there is great potential for the combination of the two. In this aspect, Daiichi-Sankyo and Merck are more strategic and forward-thinking.In August this year, Daiichi Sankyo announced that it would co-develop the bispecific antibody MK-6070 targeting DLL3/CD3 with its partner Merck. Merck and Daiichi Sankyo will now jointly develop and commercialize MK-6070 globally, but Merck will retain exclusive rights in Japan. Meanwhile, Merck will...Responsible for the production and supply of this experimental drug, the two companies will jointly share the costs of research and development and commercialization.Why Did Daiichi-Sankyo Introduce the TCE Bispecific Antibody？》. MK-6070, also known as HPN328, is a drug that Merck acquired from Harpoon earlier this year. In SCLC patients, an initial low dose of 1mg was administered, followed by the full dose. The bORR (confirmed + unconfirmed) for this therapy was 54%, with a confirmed ORR of 35%.
Of course, in addition to the B7-H3 ADC for the treatment of SCLC introduced in the article, the competition for ADCs related to this target is still very intense. Currently, 10 drugs have entered clinical trials, including those from Innovent and Mabwell, which have already entered clinical stages.
