1) The prognosis for refractory/relapsed LBCL not suitable for curative treatment is poor. The success of CD20×CD3 TCE mosunetuzumab combined with CD79b ADC polatuzumab vedotin in Phase 3 has provided patients with a novel, fixed-cycle, outpatient therapy. (Mosunetuzumab plus polatuzumab vedotin in transplant-ineligible refractory/relapsed large B-cell lymphoma: primary results of the phase 3 SUNMO trial)In the Phase 3 SUNMO study, patients with refractory/relapsed LBCL who were not suitable for autologous stem cell transplantation were randomly assigned in a 2:1 ratio to receive Mosun-Pola or rituximab, gemcitabine, and oxaliplatin (R-GemOx). The design included dual primary endpoints of ORR and PFS, with OS as a key secondary endpoint.A total of 208 subjects participated in the randomization, with Mosun-Pola and R-GemOx comprising 138 and 70 cases, respectively. The median follow-up was 23.2 months. 1) Efficacy, Mosun-Pola significantly improved mPFS (11.5 months [95% confidence interval (CI), 5.6–18] vs 3.8 months [95% CI, 2.9–4.1]; hazard ratio for progression or death, 0.41 [95% CI, 0.3–0.6]; P<0.0001), and significantly increased ORR (70% vs 40%; P<0.0001), with a complete response rate of 51% and 24%, respectively; 2) Safety, Mosun-Pola had a G2 CRS incidence of less than 5% when managed with tocilizumab, and it can improve PRO.The results replicated the Phase 2 findings; however, it is regrettable that the OS interim analysis did not reach statistical significance, leaving one final testing opportunity. Roche’s other CD20×CD3 combined with GemOx achieved statistical benefits in OS, but the safety profiles and compliance of the two regimens differ, making either regimen a good treatment option.2) Another ADC + TCE combination clinical strategy is MSD’s layout:MK-6070 + I-Dxd (DLL3 TCE + B7H3 ADC), for early clinical Phase 1/2 exploration in SCLC (NCT06780137).Referring to Amgen’s WCLC data: The Phase 1b study DeLLphi-303 explored the efficacy and safety of Tarlatamab as a maintenance add-on therapy for patients with IL SCLC who had received 4-6 cycles of treatment without progression. The results showed that among the 88 participants, mPFS was 5.6 months (95% CI, 3.5-9.0), and mOS was 25.3 months.Considering that the mPFS calculation here starts from the initiation of maintenance therapy, the total 1L mPFS should be increased by 3-4 months to 8-10 months. Compared to advanced first-line SCLC mPFS of ~5-7 months and mOS of ~12-15 months, this value suggests that DLL-3 TCE PFS to OS benefits can continue to enhance (m more), indicating that DLL-3 TCE is beneficial for later-line treatment gains.In summary, I believe DLL-3 TCE will become a very important early-line backbone for SCLC. Of course, chemotherapy is crucial, so MSD’s combination of the hottest B7H3 ADC for SCLC demonstrates the rationality and superiority of this combination.This viewpoint is further supported by Merck’s B7H3 ADC WCLC SCLC Phase 2 study.B7H3 ADC I-DXd was used in the R/R SCLC Phase 2 IDeate-Lung01 study, which included SCLC subjects who had previously received 1-3 lines of treatment (at least including 1 line of platinum-based chemotherapy), randomly assigned in a 1:1 ratio to receive I-DXd 8mg/kg or 12mg/kg intravenous treatment (Q3W), with the expansion part receiving I-DXd 12mg/kg intravenous treatment (Q3W). The primary endpoint was ORR assessed by BICR.The results showed that the confirmed objective response rate (ORR) was 48.2% (95% confidence interval: 39.6-56.9), disease control rate (DCR) was 87.6% (95% confidence interval: 80.9-92.6), median duration of response (DOR) was 5.3 months (95% confidence interval: 4.0-6.5), and median time to response (TTR) was 1.4 months (range: 1.0-8.1); similar efficacy was observed in key subgroups (see table). The median progression-free survival (PFS) and median overall survival (OS) were 4.9 months (95% confidence interval: 4.2-5.5) and 10.3 months (95% confidence interval: 9.1-13.3), respectively.Among the subgroup of patients who had previously received Tarlatamab, the cORR was higher (71.4% vs 46.9%), mPFS (5.6m vs 5.1m), but the sample size was very small (7 vs 130).