ORR signals dominated Junshi Biosciences’ AACR update: in first‑line metastatic colorectal cancer, JS207 plus XELOX produced a 71.0% objective response rate and 96.8% disease control among 31 evaluable patients; in first‑line advanced hepatocellular carcinoma, JS207 plus JS007 achieved a 45.5% ORR and 86.4% disease control across 22 evaluable patients. In the first‑in‑human phase 1/2 study of the EGFR/HER3 bispecific ADC JS212, dose cohorts at 4.2 mg/kg and 4.6 mg/kg showed ORRs of 44.4% and 50.0% with 100% disease control, including 50.0% ORR in HER2‑negative breast cancer and 38.9% in esophageal squamous cell carcinoma. No dose‑limiting toxicities were observed for JS207 combinations, JS212’s maximum tolerated dose was not reached, and key time‑to‑event endpoints remain immature.
The company’s core news at AACR is a coordinated data drop across three “IO 2.0” assets: the anti‑PD‑1/VEGF bispecific JS207 in two phase 2 combination settings and the first human efficacy signals for JS212, a bispecific EGFR/HER3 ADC now cleared for U.S. clinical development. While sample sizes are small and follow‑up short, the mCRC response rate materially exceeds historical chemotherapy ± bevacizumab benchmarks, and the HCC signal lands in the competitive range of current PD‑1 plus anti‑angiogenic regimens. The ADC readout, albeit from selected dose cohorts, points to cross‑histology activity with clean early tolerability, an increasingly rare combination in the ADC class.
Strategically, Junshi is leaning into consolidation: building intrinsic VEGF blockade into a PD‑1 backbone to simplify doublet immunotherapy and layering CTLA‑4 or chemotherapy where biology suggests a cold microenvironment. This mirrors, and directly competes with, the ivonescimab thesis in PD‑1/VEGF bispecifics and could offer operational advantages over free‑antibody combinations if the efficacy holds. Parallel movement into a bispecific ADC targeting EGFR and HER3 positions the company against established HER3‑DXd programs while aiming at resistance niches that have blunted single‑target ADCs. The through‑line is to create registrational paths that do not rely on fragile triplets, complex sequencing, or biomarker micromarkets.
For sites and CROs, the near‑term impact is increased demand for combination‑heavy, multi‑cohort designs with intensive imaging and AE surveillance. PD‑1/VEGF programs bring familiar hypertension/proteinuria and bleeding risk management plus immune‑related AE adjudication; adding CTLA‑4 raises the bar on endocrinopathies and hepatotoxicity monitoring in HCC. The JS212 program will require robust ILD vigilance, dermatologic and GI toxicity management, and potentially central testing for EGFR/HER3 expression if enrichment enters later phases. Sponsors and regulators will be focused on comparator selection: first‑line HCC now expects atezolizumab plus bevacizumab or other IO/VEGF standards, and first‑line mCRC is fragmented by RAS and sidedness, making stratification and endpoint hierarchy pivotal. Manufacturing and CMC readiness for an EGFR/HER3 ADC will be a gating factor if dose selection converges quickly.
The next milestones are durability and randomized confirmation. In mCRC, early depth of response needs to translate into progression‑free survival across RAS subgroups; in HCC, overall survival and bleeding risk under CTLA‑4 triplet pressure will drive regulatory credibility. For JS212, watch for dose selection, payload‑related safety at scale, and whether activity persists beyond selected cohorts and into resistance‑defined populations such as post‑EGFR TKI NSCLC. Competitive timing also matters: global PD‑1/VEGF bispecifics and HER3‑targeted ADCs are advancing; Junshi’s ability to initiate ex‑China studies rapidly, lock in comparators acceptable to U.S./EU regulators, and stand up ADC supply will determine whether these encouraging early signals convert into registrational momentum.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
