Chinese PD-(L)1/VEGF Bispecific Antibodies Take Center Stage at ESMO 2025 with Pivotal Clinical Data

Akeso Ivacitinib

At the chairman's seminar of this conference, Akeso announcedIvonescimab Combined with ChemotherapyFirst-line Treatment for Squamous Non-Small Cell Lung Cancer（NSCLC）Data from Phase III Clinical Trial HARMONI-6.At the same time, the research成果 has been simultaneously published in the main issue of the international top medical journal "THE LANCET".

HARMONI-6 is aRandomized, Controlled, Multicenter Phase III Clinical Study, Aiming to EvaluateIvokibant（ AK112）Efficacy and Safety of Combined Chemotherapy vs. PD-1 Inhibitor Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Squamous NSCLC.

ResearchThe primary endpoint isComparisonIvonescimabCombined Chemotherapy and Tislelizumab Combined ChemotherapyAs a first-line treatment for locally advanced or metastatic squamous NSCLC byIndependent Imaging Review Committee (IRRC) Assessed according to RECIST v1.1 criteriaProgression-Free Survival (PFS). Overall Survival (OS) Is a key secondary endpoint.

HARMONi-6 study enrolled 532 subjects, with balanced baseline between the two groups; 92.3% of the subjects were at clinical stage IV; squamous cell carcinoma characteristics were consistent with clinical reality, among which central-type squamous cell carcinoma accounted for approximately 63%.(Akeso group 66.9% vs Tislelizumab group 59.4%), consistent with the distribution of patients in the real world; the proportion of PD-L1 expression aligns with clinical reality.

The research results show that the combination of Ivonesc with chemotherapy compared to the combination of Tislelizumab with chemotherapyAchieved the Primary Endpoint of PFS, achieving a decisive victory with strong positive results, demonstrating statistically significant benefits and significant clinical benefits. The combination of Ivonesc with chemotherapy showed superiority over the combination of Tislelizumab with chemotherapy.Significantly Extend Patients' Progression-Free Survival。

Data show that the combination of AKESO's Ivonescimab and chemotherapy as a first-line treatment for sq-NSCLC in the trial group...mPFS up to 11.14 months，The mPFS of the control group treated with Tislelizumab combined with chemotherapy was 6.90 months, and the HARMONi-6 study achievedInter-group PFS absolute value improvement △PFS = 4.24 months。

Regardless of PD-L1 expression level(PD-L1 negative or positive)，Ivonescib combined with chemotherapy showed significant benefit compared to Tislelizumab combined with chemotherapy. InPD-L1 Negative（TPS＜1%）In the population, the intergroup comparison between the experimental group (Ivonesc in combination with chemotherapy) and the control group (Tislelizumab in combination with chemotherapy) PFS HR=0.55; InPD-L1 Positive（TPS≥1%）PFS Between the Experimental Group (Akeso + Chemotherapy) and the Control Group (Tislelizumab + Chemotherapy) in the PopulationHR=0.66。

Regardless of whether liver metastasis is present or the number of baseline metastatic sites, the combination of Ivonescimab with chemotherapy showed significantly greater benefit compared to Tislelizumab combined with chemotherapy.In the population with liver metastases, the intergroup PFS HR=0.53; in the population without liver metastases, the intergroup PFS HR=0.64; in the population with ≥3 baseline metastatic sites, the intergroup PFS HR=0.46; in the population with <3 baseline metastatic sites, the intergroup PFS HR=0.64.

The overall safety of the Ivonesc group was good, with no new safety signals identified. The incidence rates of serious adverse events related to treatment, immune-related adverse events, and grade 3 or higher bleeding events were similar to those in the tislelizumab regimen group. The most common adverse reactions were chemotherapy-related myelosuppression.

3SBIOINCSSGJ-707

At this conference, 3SBIOINC announcedPD1/VEGF Bispecific Antibody SSGJ-707 Combined ChemotherapyAsMetastatic Colorectal Cancer (mCRC) Patient First-Line TreatmentPhase II Clinical Trial (NCT06493760) Preliminary results.

In the study, untreated left half(Including rectal tumors)Patients with RAS/RAF mutationsAnd the right half(Regardless of RAS/RAF mutation status)Patients with pMMR/MSS-type mCRC were randomly assigned in a 1:1:1:1 ratio to receive SSGJ-707 10 mg/kg Q3W + XELOX treatment.(A1 Group)SSGJ-707 10 mg/kg Q2W + mFOLFOX6 Treatment(A2 Group)SSGJ-707 5 mg/kg Q3W+XELOX Treatment(B1 Group)Or SSGJ-707 5 mg/kg Q2W + mFOLFOX6 treatment(B2 Group)。The primary endpoints are ORR and safety.。

As of February 18, 2025, 68 patients with mCRC have been treated with SSGJ-707 in combination with chemotherapy at a dose of 10 mg/kg Q3W.（n=18）、10 mg/kg Q2W（n=16）、5 mg/kg Q3W（n=17）、5 mg/kg Q2W（n=17）The median age of the patients was 61.5 years, and 70.6% of the patients had an ECOG PS score of 1. The primary tumor site was left-sided CRC in 60.3% of the patients and right-sided CRC in 39.7%. In 45.6% of the patients, the PD-L1 CPS score was ≥1.

Safety data showed that, out of 68 patients, 61 cases（89.7%）TRAE occurred, 19 cases（27.9%）≥3 Grade TRAE occurred. The most common TRAE（≥20%）Including increased aspartate aminotransferase, anemia, decreased neutrophil count, increased alanine aminotransferase, decreased platelet count, and decreased white blood cell count. Treatment-related adverse events (TRAE) leading to treatment delay occurred in 25% of patients, with no TRAE leading to treatment discontinuation.

Screenshot source: Insight database

In summary, the study suggests that SSGJ-707 combined with XELOX/mFOLFOX6 regimens demonstrates promising efficacy in first-line treatment of metastatic colorectal cancer (mCRC) with manageable safety. Ongoing studies are evaluating SSGJ-707 monotherapy for ≥3rd-line mCRC and its combination with chemotherapy as a first-line treatment for all pMMR/MSS-type mCRC.