GEN1055 First-in-Human Trial Results Posted: No Dose-Limiting Toxicities in Terminated Solid Tumor Study

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Genmab reported the first results from its GEN1055 first-in-human trial on ClinicalTrials.gov on August 11, 2026 , covering 21 participants with malignant solid tumors who received monotherapy across four dose cohorts, showing zero dose-limiting toxicities . No objective tumor responses were recorded in any dose group , leaving the clinical significance of the bispecific antibody uncertain despite an acceptable safety profile in the dose-escalation phase .

ClinicalTrials.gov first posted the results table for NCT06391775 on August 11, 2026 , making the safety and efficacy data public before any peer-reviewed publication.

Enrolled

21

ClinicalTrials.gov →

DLTs

0

ClinicalTrials.gov →

Objective Responses

0

ClinicalTrials.gov →

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English · ENG

AI-generated conceptual illustration; not study data.

GEN1055 Dose-Escalation Safety and Activity

Study design: First-in-human, open-label, dose escalation with expansion cohorts (PHASE1/PHASE2)

Enrolled population: 21 participants with malignant solid tumors across four GEN1055 dose cohorts (10 mg, 30 mg, 100 mg, 200 mg IV every 3 weeks)

Analysis population: Safety analysis set: 21 participants (all treated); Response-evaluable set: participants with baseline and postbaseline disease assessments

Primary endpoint: Number of participants with adverse events and dose-limiting toxicities (DLTs) during the three-week DLT evaluation period

The safety analysis included all participants who received GEN1055 monotherapy across four IV dose cohorts (10, 30, 100, 200 mg every three weeks). No dose-limiting toxicity occurred during the three-week DLT window in any cohort, so the primary safety objective of the dose-escalation phase was met.

The no-DLT result is based on all participants in the safety analysis set. Each cohort was monitored for predefined DLT criteria over three weeks, including grade 5 events, grade 3-or-higher infusion reactions, severe hematologic toxicity, and Hy’s law cases; none met these thresholds.

Despite a favorable safety profile, no participant achieved a confirmed RECIST v1.1 response in any cohort (overall response rate was 0%). Disease control was seen in the 100 mg cohort (50%, 95% CI 11.8 to 88.2) and 200 mg cohort (33%, 95% CI 4.3 to 77.7).

AI-generated conceptual illustration; not study data.

A dose-escalation study tests escalating doses in small cohorts to find tolerated dose levels. A fixed dose is given to one cohort at a time, and investigators advance only after predefined toxicity criteria are met. This trial was open-label and non-randomized, so participants and investigators were aware of assigned dose.

Adverse events were frequent: Non-serious adverse events were reported among treated participants. Anti-drug antibodies were reported, indicating an immunogenicity signal whose clinical significance was not further characterized in the registry report.

Genmab, an industry sponsor developing antibody-based therapeutics , designed GEN1055 as a bispecific antibody targeting two antigens. The trial enrolled participants in Spain and the United States between May 2024 and November 2025.

Zero Responses in a Bispecific Antibody Program

The absence of objective tumor responses in a first-in-human dose escalation trial does not necessarily signal failure of the drug candidate. Dose escalation studies are primarily designed to establish safety and identify a recommended phase 2 dose, not to measure definitive efficacy. The small sample sizes within each dose cohort limit the statistical power to detect meaningful activity signals.

The disease control rate of 50 percent at the 100 mg dose suggests that tumor stabilization occurred in some participants, but the wide confidence interval spanning from 11.8 to 88.2 percent reflects the uncertainty inherent in a six-person cohort. Without a randomized comparator, it is not possible to determine whether stable disease reflects drug activity or the natural disease course in patients with advanced solid tumors.

The termination of the trial for strategic reasons raises questions about the future of the GEN1055 program. The combination arms with pembrolizumab and the expansion cohorts were never initiated, meaning the potential synergistic activity of GEN1055 alongside checkpoint inhibition remains untested. Strategic decisions by sponsors to terminate trials can reflect portfolio priorities, competitive landscape shifts, or internal efficacy assessments that are not captured in the registry data.

For patients with malignant solid tumors who have exhausted standard therapies, early-phase trials represent a treatment access pathway, but the zero response rate underscores the need for realistic expectations about investigational agents. The safety data may inform future combination strategies if the program continues in a different form.

Safety Profile and Trial Limitations

While no dose-limiting toxicities were observed, the safety data reveal a population with significant disease burden. Deaths occurred during the study period; the registry does not establish that GEN1055 directly caused them. Serious adverse events were reported, including increased aspartate aminotransferase, urinary tract infection, viral meningoencephalitis, anemia, and infusion-related reaction.

The safety analysis set included all treated participants, but the deaths and serious adverse events must be interpreted in the context of an advanced cancer population with progressive disease after prior platinum-based chemotherapy and anti-PD-1 or PD-L1 therapy. The absence of dose-limiting toxicities across all four dose levels suggests a tolerable safety profile at the tested doses, though the observed anti-drug antibody signal warrants further investigation if development continues.

AI-generated conceptual illustration; not study data.

The most significant limitation is that the trial was terminated early and only the monotherapy dose escalation portion was conducted. The planned combination cohorts with pembrolizumab and standard chemotherapy were never initiated, and the dose expansion phase designed to evaluate efficacy in specific tumor indications was not executed. This means the available data cover only a small, heterogeneous population across multiple tumor types rather than a focused efficacy assessment in a selected indication.

The registry results have not undergone peer review, and the sponsor noted a restrictive agreement governing publication. Readers should treat registry-posted results as preliminary and subject to revision when the full analysis appears in a peer-reviewed journal, if it is published at all.

Uncertain Path Forward for GEN1055 Development

The strategic termination leaves the GEN1055 development trajectory unclear. Genmab has not publicly disclosed whether the bispecific antibody platform will be deprioritized entirely or whether alternative trial designs or combination strategies are being considered. The safety data from this trial, showing tolerability up to 200 mg without dose-limiting toxicities, could theoretically support future studies if the program is revived.

The absence of combination data is particularly notable because bispecific antibodies are often developed for use alongside checkpoint inhibitors, and the planned GEN1055 plus pembrolizumab cohorts could have provided a different efficacy profile. Whether the zero monotherapy response rate would have been different in combination remains an open question that the current data cannot address.

For the broader field of bispecific antibody development in oncology, the GEN1055 results add to the growing body of early-phase data showing that safety alone does not guarantee efficacy. The gap between tolerability and tumor response highlights the challenge of translating bispecific antibody design into clinical benefit for patients with refractory solid tumors.

Clinical trial registration does not equal validated results. Registry-posted results have not undergone peer review. Disease control does not equal tumor response. The absence of dose-limiting toxicities does not confirm therapeutic benefit. Anti-drug antibody detection does not necessarily indicate loss of efficacy.

References: ClinicalTrials.gov NCT06391775 — Results

This article is not medical advice. Consult a qualified healthcare provider for clinical decisions.