お知らせ • Apr 22
Shanghai Junshi Biosciences Co., Ltd Presents Results from JS207 (PD-1/VEGF BsAb) Phase 2 Combo Studies and JS212 (EGFR/HER3 ADC) FIH Phase 1/2 Study at AACR 2026
Shanghai Junshi Biosciences Co., Ltd. announced that early clinical results from four studies across its innovative pipeline were presented at the 2026 American Association for Cancer Research (AACR) Annual Meeting, featuring: the recombinant humanized anti-EGFR/HER3 bispecific antibody-drug conjugate (ADC) JS212, the anti-PD-1/VEGF bispecific antibody JS207, and the anti-CTLA-4 monoclonal antibody JS007. The Phase 2 study (NCT06954467) aiming to evaluate the safety and efficacy of JS207 in combination with JS007 included a safety run-in period and a randomized expansion phase, which enrolled patients with unresectable or metastatic HCC who had not previously received any systemic anticancer therapy. As of March 20, 2026, a total of 26 patients had received JS207 plus JS007, including 7 patients in the safety run-in period and 19 patients in the randomized expansion phase. Among the 22 evaluable patients, the objective response rate (ORR) reached 45.5% while the disease control rate (DCR) was 86.4%. JS207 plus JS007 was well-tolerated, with no dose-limiting toxicities (DLT) observed during the safety run-in period. Preliminary findings from the study demonstrate that JS207 combined with JS007 exhibits encouraging synergistic efficacy and favorable tolerability as first-line treatment for advanced HCC. Patient enrollment continues to progress smoothly, potentially offering a novel therapeutic approach for advanced HCC patients. This Phase 2 study (NCT06885385) evaluates the preliminary safety and efficacy of JS207 in combination with XELOX (capecitabine + oxaliplatin) as first-line therapy for mCRC. The study enrolled patients with mCRC who had not previously received systemic antitumor therapy for metastatic disease, or whose disease recurred/progressed at least 12 months after their last neoadjuvant/adjuvant therapy. Patients received JS207 at 10 mg/kg combined with the XELOX regimen (oxaliplatin 130 mg/m² IV, d1 + capecitabine 1000 mg/m², BID, d1-14) every 3 weeks until disease progression or intolerable toxicity. As of January 13, 2026, 32 patients had been enrolled and received JS207 plus XELOX, including 9 in the safety run-in phase and 23 in the dose-expansion phase. Among the 31 efficacy-evaluable patients, 22 achieved a partial response (PR) and 8 achieved stable disease (SD), resulting in an ORR of 71.0% and a DCR of 96.8%. Due to the relatively short follow-up duration, median progression-free survival (PFS) and median duration of response (DoR) have not yet been reached, and the longest duration of response remained ongoing at 8 months. JS207 was well-tolerated overall, with no DLTs observed during the safety run-in period. The study demonstrates that JS207 combined with chemotherapy exhibits promising antitumor activity and a favorable safety profile as first-line treatment for mCRC. These findings suggest that dual-target immunotherapy (anti-PD-1/VEGF) plus chemotherapy holds significant potential in immunologically cold tumors, providing critical clinical evidence for immuno-combination therapy as first-line treatment of mCRC. Preclinical studies of JS212 (EGFR/HER3 bsAb) demonstrate high binding affinity to tumor cells expressing EGFR and/or HER3, exhibiting superior broad-spectrum antitumor activity, favorable tolerability, and optimal pharmacokinetic profiles. In multiple cell-derived xenograft (CDX) models, JS212 showed enhanced antitumor efficacy compared to the benchmark agent. Notably, it demonstrated efficacy in osimertinib-resistant, patritumab deruxtecan-resistant, and BL-B01D1-resistant CDX models. This FIH phase 1/2 study (NCT06888830) was designed to assess the safety, tolerability, PK, and preliminary efficacy of JS212 in patients with advanced solid tumors. It comprised dose escalation and expansion and clinical expansion. As of March 26, 2026, a total of 63 patients have been enrolled. JS212 was administered every three weeks. The treatment was well-tolerated, and the maximum tolerated dose (MTD) was not reached. Responses were observed at the 1.8 mg/kg cohort and above. In the 4.2 mg/kg and 4.6 mg/kg dose cohorts, ORR reached 44.4% and 50.0% respectively, with a DCR of 100.0% in both groups. The median DoR has not yet been reached. An ORR of 50.0% was observed in HER2-negative breast cancer and 38.9% in esophageal squamous cell carcinoma. JS212 monotherapy exhibits encouraging efficacy across a range of dose levels (as low as 1.8 mg/kg) with favorable tolerability in advanced solid tumors, indicating promising development potential. Further exploration of JS212 in multiple indications and combination strategies are ongoing. JS207, a recombinant humanized anti-PD-1/VEGF bispecific antibody, was independently developed by Junshi Biosciences for the treatment of advanced malignant tumors. To date, JS207 has been approved for conducting phase 2/3 clinical study, and it has 11 ongoing phase 2 clinical studies, exploring its use in combination with chemotherapy, monoclonal antibodies, ADCs and other drugs in NSCLC, colorectal cancer, triple-negative breast cancer, liver cancer and other tumor types. Preclinical results of JS207 have been published in Frontiers in Immunology, while early-stage clinical data were first presented in a poster session at ESMO ASIA 2025. JS207 can simultaneously bind to PD-1 and VEGFA with high affinity, effectively blocking the binding of PD-1 to PD-L1 and PD-L2 while also inhibiting the binding of VEGF to its receptor. JS207 has the efficacy of both immunotherapeutic drugs and anti-angiogenic drugs. Through the neutralization of VEGF, JS207 inhibits the proliferation of vascular endothelial cells, improves the tumor microenvironment, and increases the infiltration of cytotoxic T lymphocytes in the tumor microenvironment, thereby achieving better anti-neoplasm activity. JS207’s design is based on the high-affinity, clinically proven and differentiated anti-PD-1 drug, toripalimab as the backbone. The anti-PD-1 moiety of JS207 adopts a Fab structure to maintain binding affinity to PD-1, thereby attaining better enrichment in the tumor microenvironment. The anti-VEGF moiety has a binding affinity for human vascular endothelial growth factor that is comparable to that of bevacizumab. In non-clinical in vitro cytological tests, compared with the combination of an anti-PD-1/PD-L1 monoclonal antibody and a VEGF monoclonal antibody, a bispecific antibody simultaneously targeting PD-1/PD-L1 and VEGF demonstrated significantly enhanced PD-1 antigen binding and internalization, as well as synergistic enhancement of the NFAT signaling pathway, thereby better activating immune cells in the tumor microenvironment. JS007 is a recombinant humanized anti-CTLA-4 monoclonal antibody developed independently by Junshi Biosciences that is mainly aimed at treating advanced cancer.
