Target Pair ◆ dll3-cd3
DLL3 × CD3DRAFT
数据列表以英文版为准（Grade A/B 证据，见 gp-master）。
1 · 概览
活跃资产: 6 ｜ 公司: 6 ｜ 事件: 7
83
机会评分黄金
≥80 黄金 / 65–79 观察 / <65 持有（五维加权，方法论见 gp-master）
2 · 为什么值得做
T 细胞衔接器参照配对：DLL3 是 SCLC/神经内分泌肿瘤富集的肿瘤选择性 Notch 配体；tarlatamab（Amgen）已获批（2024 加速 → 2025 全面 → NMPA 2026），≥3 个临床竞品——标准 TCE 基准配对。
3 · 资产格局
- 01Tarlatamab (Imdelltra) — Amgen, DLL3×CD3 BiTE, FDA accel 2024-05 → full 2025-11 → EC 2025 → NMPA 2026-04 (BeOne/BeiGene)
- 02Gocatamig/MK-6070 — Merck (Harpoon TriTAC), Ph1/2 (ORR 44%)
- 03Obrixtamig/BI 764532 — Boehringer, IgG-like TCE, Ph1 → Ph3 (DAREON-Lung-1)
- 04QLS31904 — Qilu, Phase 1
- 05Henlius tetra-specific TCE — newly in clinic
- 06(failed precedent: Rova-T — DLL3 ADC, AbbVie/Stemcentrx, $5.8B acquisition, terminated 2019)
4 · 公司
- 01Amgen (tarlatamab)
- 02Merck (gocatamig, Harpoon $680M 2024)
- 03Boehringer Ingelheim (obrixtamig)
- 04Qilu (QLS31904)
- 05BeiGene/BeOne (China partner)
- 06Henlius
5 · 临床与交易事件
| 日期 | 事件 | 公司 |
|---|---|---|
| 2019 | Rova-T (DLL3 ADC) terminated after $5.8B AbbVie/Stemcentrx failure | AbbVie |
| 2024-01 | Merck–Harpoon deal (~$680M, gocatamig) | Merck/Harpoon |
| 2024-05-16 | tarlatamab FDA accelerated approval | Amgen |
| 2025-06 | DeLLphi-304 Ph3 positive: ~40% death-risk reduction (2L SCLC) | Amgen |
| 2025-08 | BeOne–Royalty Pharma ~$885M upfront (scope ambiguity flagged) | BeOne/Royalty |
| 2025-11 | tarlatamab full approval | Amgen |
| 2026-04 | tarlatamab NMPA approval (China) | BeOne/BeiGene |
6 · 风险与失败
- 01Rova-T precedent: DLL3 ADC $5.8B failure (2019) — DLL3 biology challenges
- 02DLL3 expression heterogeneity (HOT1702: only 47% DLL3-high)
- 03CRS ~51% any grade (TCE class)
- 04TCE manufacturability / chain-pairing risks
- 05Generic DLL3/CD3 proteins and bridging ELISA already commoditized (ACRO/Sino) — tool gap is narrow
7 · 研发问题
- 01DeLLphi-302/305/306 detailed designs and readouts (labeling conflated in secondary press)
- 02DLL3 ECD 'difficult expression' — quantified yield/stability data (Grade B/C)
- 03CD3ε vs CD3δ arm format comparison for DLL3 TCEs (no public data)
- 04CRS management / step-up dosing strategy across competitors
8 · 研究工具
- 01DLL3 ECD — expression-difficult (tool gap: quantified yield/stability)
- 02CD3E (CD3E/CD3D) — mature formats
- 03Human/Cyno cross-species
- 04Dual-binding SPR/BLI + bridging assay
- 05T-cell activation / CRS-relevant functional assay (S03)
9 · 实验工作流
结合 → 双结合 → 功能（PRD §20 §9）。
10 · 服务
11 · 证据
最近审校: 2026-08-19 ｜ 置信度: high ｜ 证据: Score 83/100 = Golden (PRD §7); Grade A/B only; full ledger in gp-master
完整证据台账: gp-master/GP-03_dll3-cd3.md（本仓库 docs/artifacts/gp-master/，未托管外链）
下一步