Therapeutic Potential of Bispecific Antibodies in Adenocarcinoma: A Targeted Literature Review
Author(s)
Nallamothu Bhargavi, Ph.D.1, Reddy Reddikumar, M. Pharm1, Kapil Maheshchandra KHAMBHOLJA, Ph.D.2, VATSAL AKHILESH CHHAYA, M.S.2.
1Medical Writing, Catalyst Clinical Research, Trivandrum, India, 2Medical Writing, Catalyst Clinical Research, Vadodara, India.
1Medical Writing, Catalyst Clinical Research, Trivandrum, India, 2Medical Writing, Catalyst Clinical Research, Vadodara, India.
OBJECTIVES: To assess the clinical evidence supporting bispecific antibodies (BsAbs) in adenocarcinomas, focusing on efficacy outcomes, safety profiles, and therapeutic combinations in early-phase studies
METHODS: A targeted literature search was conducted using the PubMed database and supplemented with internet searches of relevant clinical trial registries, conference proceedings, and organizational websites. Additionally, bibliographies of key systematic reviews and meta-analyses were manually screened to identify additional studies of interest.
RESULTS: The studies involving bispecific antibodies predominantly focused on gastric/GEJ adenocarcinoma (n=5), hepatocellular carcinoma (n=3), pancreatic cancer (n=2), lung adenocarcinoma (n=2), and single studies in prostate, medullary thyroid carcinoma, and HER2-positive cancers. Molecules more frequently studied are AK104 (PD-1/CTLA-4 bispecific), zanidatamab (anti-HER2), and CDX-527 (PD-L1/CD27). ORRs ranged from 37% to 72.7%, with select studies reporting complete responses. In gastric/GEJ adenocarcinoma, AK104-based combinations achieved ORRs up to 65.9%, with median PFS of 7.1 months and OS of 17.4 months. In hepatocellular carcinoma, AK104 plus lenvatinib achieved a disease control rate (DCR) of 77.8%. Median OS exceeded 30 months in select prostate and pancreatic adenocarcinoma cohorts. Safety profiles varied, but most TRAEs were grade 1-2, including cytopenia, transaminase elevations, and infusion reactions. Grade ≥3 TRAEs occurred in up to 72.7% of patients. Two treatment-related deaths were reported.
CONCLUSIONS: Our findings indicate promising efficacy of BsAbs in gastric, hepatic, and HER2-positive adenocarcinomas, with encouraging disease control and survival outcomes. While most TRAEs were manageable, frequent higher-grade events highlight the need for close monitoring. Biomarker-enriched trials may help optimize safety and patient selection.
METHODS: A targeted literature search was conducted using the PubMed database and supplemented with internet searches of relevant clinical trial registries, conference proceedings, and organizational websites. Additionally, bibliographies of key systematic reviews and meta-analyses were manually screened to identify additional studies of interest.
RESULTS: The studies involving bispecific antibodies predominantly focused on gastric/GEJ adenocarcinoma (n=5), hepatocellular carcinoma (n=3), pancreatic cancer (n=2), lung adenocarcinoma (n=2), and single studies in prostate, medullary thyroid carcinoma, and HER2-positive cancers. Molecules more frequently studied are AK104 (PD-1/CTLA-4 bispecific), zanidatamab (anti-HER2), and CDX-527 (PD-L1/CD27). ORRs ranged from 37% to 72.7%, with select studies reporting complete responses. In gastric/GEJ adenocarcinoma, AK104-based combinations achieved ORRs up to 65.9%, with median PFS of 7.1 months and OS of 17.4 months. In hepatocellular carcinoma, AK104 plus lenvatinib achieved a disease control rate (DCR) of 77.8%. Median OS exceeded 30 months in select prostate and pancreatic adenocarcinoma cohorts. Safety profiles varied, but most TRAEs were grade 1-2, including cytopenia, transaminase elevations, and infusion reactions. Grade ≥3 TRAEs occurred in up to 72.7% of patients. Two treatment-related deaths were reported.
CONCLUSIONS: Our findings indicate promising efficacy of BsAbs in gastric, hepatic, and HER2-positive adenocarcinomas, with encouraging disease control and survival outcomes. While most TRAEs were manageable, frequent higher-grade events highlight the need for close monitoring. Biomarker-enriched trials may help optimize safety and patient selection.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
SA97
Topic
Study Approaches
Topic Subcategory
Literature Review & Synthesis
Disease
Oncology