Madrid, Spain, October 23‑27, 2026 — Three early‑phase clinical studies presented at the 2026 European Society for Medical Oncology (ESMO) Congress reported preliminary efficacy and safety profiles for novel antibody‑drug conjugates (ADCs), including combination regimens and bispecific ADCs (BsADCs), in patients with advanced solid tumors. A Phase II trial reported an objective response rate (ORR) of 80.6% in the platinum‑resistant ovarian cancer cohort treated with B7‑H3‑targeted ADC elfetabart drozuntecan plus PD‑L1/VEGF‑A bispecific antibody pumitamig, while the cervical cancer cohort achieved an ORR of 50.0%. Two Phase I trials of EGFR/cMET‑ and EGFR/B7‑H3‑targeted bispecific ADCs also demonstrated antitumor signals across non‑small‑cell lung cancer and other solid malignancies. All findings represent early‑phase signals; durability of response and long‑term safety remain to be validated.
B7‑H3‑Targeted ADC Plus Bispecific Antibody: Encouraging Activity in Gynecologic Malignancies
B7‑H3 is overexpressed in multiple tumor types and constitutes a high‑priority target for ADC development. This global Phase II study evaluated elfetabart drozuntecan (ElfeD; DB1311/BNT324), a B7‑H3‑directed ADC, combined with pumitamig, a PD‑L1/VEGF‑A bispecific antibody. The combination aims to deliver synergistic cytotoxic, immunomodulatory and anti‑angiogenic effects.
Safety population included 142 patients, and 139 were evaluable for efficacy. Median follow‑up was 6.3 months. The overall unconfirmed ORR reached 48.9% (95% CI, 40.4%‑57.5%). Key cohort‑level unconfirmed ORR data are as follows:
Platinum‑resistant ovarian cancer (n=31): 80.6%
Cervical cancer (n=22): 50.0%
Hepatocellular carcinoma (n=21): 42.9%
Head‑and‑neck malignancies (n=39): 38.5%
Melanoma (n=26): 30.8%
Meaningful responses were observed even among patients previously treated with immunotherapy or bevacizumab, with efficacy trends comparable to the overall population. Important note: these are unconfirmed ORR outcomes from small cohorts. Cross‑tumor‑type comparison is not justified, and superiority over current standard‑of‑care cannot be concluded.
No dose‑limiting toxicities were identified. Treatment‑related adverse events (TRAEs) of grade ≥ 3 occurred in 38.7% of patients; only 3.5% discontinued therapy due to TRAEs. Two interstitial lung disease (ILD)‑suspected events were reported: one was ruled out for ILD upon assessment, and the other remains under adjudication. One grade‑5 dyspnea event was judged by investigators to be unrelated to study treatment. Most patients maintained treatment for ≥6 months. Longer follow‑up is needed to characterize response durability and long‑term discontinuation rates.
While this combination yielded promising activity signals in platinum‑resistant ovarian and cervical cancer, current data are insufficient to change clinical practice.
EGFR/cMET Bispecific ADC: 55.7% ORR in EGFR‑Mutant NSCLC
Bispecific ADCs integrate two antigen‑binding moieties within one antibody scaffold, conjugated to a topoisomerase I inhibitor payload. The construct may enhance tumor internalization and counteract tumor heterogeneity, though theoretical advantages await robust clinical proof.
In the Phase I study of HS‑20122, the core cohort of EGFR‑mutant non‑small‑cell lung cancer (NSCLC) (n=106) achieved an ORR of 55.7% and disease‑control rate (DCR) of 92.5%. Within the 6 mg/kg dose group (n=31), ORR was 61.3% and the 6‑month progression‑free‑survival (PFS) rate reached 75.3%. The nasopharyngeal carcinoma cohort (n=6) reported an ORR of 66.7% and DCR of 83.3%; interpretation is cautioned given the very small sample size.
Among 215 safety‑evaluable patients, grade ≥ 3 TRAEs occurred in 44.2%, and 3.7% stopped treatment due to adverse events. Treatment‑related ILD was seen in 2.8% of subjects. This agent warrants further development; optimal dosing and benefit‑risk profile require additional investigation.
EGFR/B7‑H3 Bispecific ADC: Antitumor Signals Across Multiple Solid Tumors
Another Phase I trial assessed IBI3001, an EGFR/B7‑H3 bispecific ADC also carrying a TOP1‑inhibitor payload. Fifty‑three patients were evaluable for efficacy:
EGFR‑mutant NSCLC (n=16): ORR 31.3%, median PFS 7.7 months
Small‑cell lung cancer (n=8): ORR 62.5%, PFS data immature
Head‑and‑neck plus esophageal squamous carcinoma (n=5): ORR 60.0%, PFS data immature
Pancreatic ductal adenocarcinoma (n=15): ORR 15.4%, median PFS 6.9 months
Grade ≥ 3 TRAEs were reported in 47.4% of patients. Only one patient discontinued treatment due to TRAEs, and one grade‑2 pneumonia case was documented. Cohort sizes are limited; ORR does not equate to durable clinical benefit.
Key Unanswered Questions for Bispecific ADC Development
Data from ESMO 2026 highlight two developmental pathways: ADC plus bispecific‑antibody combinations and single‑molecule bispecific ADCs. Critical unresolved questions remain:
Is co‑expression of both target antigens required for maximal antitumor activity of bispecific ADCs?
Can observed tumor responses sustain over time?
How to identify high‑risk patients for pulmonary adverse events and optimize dosing and AE‑management strategies?
What incremental clinical benefit can novel ADC‑based strategies deliver versus established immunotherapy combinations, and which patient subgroups stand to gain most?
Concluding Remarks
These three ESMO 2026 abstracts add new evidence for ADC‑combination and bispecific‑ADC pipelines. The high response rates seen with elfetabart drozuntecan plus pumitamig represent a noteworthy signal for gynecologic‑oncology research. Caution: high early‑phase ORR does not guarantee definitive clinical benefit; confirmatory large‑scale long‑term trials are mandatory. These materials serve purely as academic updates and should not drive clinical treatment decisions.
Source: abstracts released at ESMO 2026 Congress (https://www.esmo.org). Compiled by Obstetrics‑Gynecology Network / Med‑Onc Gynecology. For academic information only, not medical advice. All investigational agents described remain in clinical development and have not obtained marketing authorization. Early‑trial data carry inherent limitations regarding efficacy and safety, which must be verified in confirmatory studies. Clinical management should follow current clinical guidelines and approved product labeling.
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