A groundbreaking advancement in cancer therapeutics is emerging from a recent international clinical trial investigating the novel targeted therapy, DB-1310. This antibody-drug conjugate (ADC) demonstrates promising efficacy in patients with advanced solid tumors, particularly those harboring EGFR-mutant non-small cell lung cancer (NSCLC), who have exhausted current standard treatment options. Led by Dr. Aaron Lisberg and his team at UCLA’s Jonsson Comprehensive Cancer Center, the trial presents compelling early-phase data suggesting DB-1310’s potential to reshape the landscape of precision oncology.
DB-1310 represents an innovative class of therapeutics leveraging an antibody engineered to specifically bind to the HER3 receptor, which is frequently overexpressed or aberrantly activated on the surface of various cancer cells. This receptor-targeted approach allows DB-1310 to deliver a cytotoxic chemotherapy payload directly to malignant cells, sparing normal tissues and thus aiming to reduce systemic toxicity commonly seen with traditional chemotherapy. This mode of selective drug delivery exemplifies the next frontier in enhancing therapeutic indices and overcoming the limitations of nonspecific cytotoxic agents.
The clinical trial enrolled 172 patients with advanced solid tumors who had previously undergone multiple lines of therapy, including chemotherapy and targeted treatments. Of these participants, a significant subset of 108 individuals had NSCLC, and within this group, 62 carried the EGFR mutation – a known driver alteration that often confers poor prognosis and resistance to conventional therapies. Importantly, 24 patients in the cohort presented with brain metastases, an area of particular clinical challenge given the protective nature of the blood-brain barrier and the concomitant lack of effective systemic options.
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At the time of data cutoff, DB-1310 was administered intravenously every three weeks in varying doses to determine the optimal balance between safety and efficacy in this first-in-human phase 1/2a study. The results revealed a remarkable 44% objective tumor response rate among patients with EGFR-mutant NSCLC, a subgroup notoriously difficult to treat after failure of FDA-approved agents. This translated into a median progression-free survival of seven months and a median overall survival nearing 19 months – metrics that surpass expectations for this heavily pretreated population.
Across the entire trial cohort, irrespective of tumor histology, the therapeutic impact remained notable with nearly one-third (31%) of patients experiencing measurable tumor shrinkage. The average duration before disease progression was observed at approximately 5.5 months, accompanied by a median overall survival of 14.4 months. These outcomes underscore DB-1310’s broad potential utility beyond lung cancer and highlight its capacity to induce clinically meaningful responses where few options remain.
Safety and tolerability are critical considerations in oncology drug development, especially for patients with advanced disease burden and compromised organ function. DB-1310’s adverse event profile was manageable, with the most frequently reported side effects being cytopenias such as low blood cell counts and mild to moderate nausea. These findings suggest that the ADC’s targeted mechanism successfully reduces off-target effects compared to conventional chemotherapy, rendering it a feasible option even for frail patients.
The scientific innovation underpinning DB-1310 lies in its sophisticated ADC design, which conjugates a potent cytotoxic agent to a monoclonal antibody selectively binding HER3. HER3, a member of the EGFR receptor family, plays a pivotal role in oncogenic signaling pathways that promote tumor cell proliferation and survival, often mediating resistance to other tyrosine kinase inhibitors. By directly trafficked delivery of a lethal drug payload into HER3-expressing cancer cells, DB-1310 circumvents these resistance mechanisms while sparing healthy cells, offering a precision strike against malignancies.
Dr. Lisberg, an assistant professor and thoracic medical oncologist, remarked that these findings mark an important milestone in the pursuit of new therapies for patients with few remaining effective options. He emphasized that the extended survival and tolerability observed even in heavily pretreated groups reveal DB-1310’s promise as a meaningful step forward. Current standard-of-care treatments frequently fail to control disease progression in patients with advanced solid tumors, highlighting the urgent need for innovative approaches such as this.
Ongoing efforts are focused on defining the optimal dosing regimen and expanding the investigation to include larger and more diverse patient populations across multiple tumor types. The phase 2 portion of the trial aims to deepen the understanding of DB-1310’s efficacy and safety profile, with the hope of confirming these encouraging preliminary results and potentially securing regulatory approval for broader clinical use. The study also includes patients with brain metastases, addressing a critical unmet need given the poor prognosis typically associated with central nervous system involvement.
The implications of DB-1310 extend beyond lung cancer, suggesting a new paradigm for targeting HER3-positive malignancies, which are prevalent in a multitude of solid tumors such as breast, head and neck, and gastrointestinal cancers. This ADC platform exemplifies how precision medicine leverages molecular biology insights to create tailored therapies that not only enhance patient outcomes but also improve quality of life by limiting detrimental side effects.
As this research is presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting during a high-profile oral abstract session, the oncology community will be closely watching the trajectory of DB-1310. The results underscore the growing importance of antibody-drug conjugates in cancer treatment, a modality that continues to revolutionize targeted cancer therapy by combining the specificity of monoclonal antibodies with the cytotoxic power of chemotherapy.
The study, sponsored by Duality Biologics, represents a collaborative effort among clinicians, researchers, and supporting teams at UCLA and around the world. The contributions from multidisciplinary experts in oncology, molecular biology, pharmacology, and clinical trial management have been instrumental in advancing DB-1310 from bench to bedside. This achievement exemplifies the dynamic translational research ecosystem driving future innovations in cancer therapeutics.
In summary, the early-phase clinical data for DB-1310 signal a potentially transformative advance in the treatment of advanced solid tumors, especially for patients with EGFR-mutated NSCLC who have exhausted existing options. The drug’s ability to induce tumor shrinkage, delay disease progression, and extend survival with a tolerable safety profile positions it as a leading candidate in the next wave of targeted cancer therapies. Further research will determine its ultimate role in the oncologic treatment armamentarium, but current evidence fosters cautious optimism for patients and clinicians alike.
Subject of Research: Advanced solid tumors treatment, targeted therapy, antibody-drug conjugate, EGFR-mutant non-small cell lung cancer (NSCLC)
Article Title: Emerging Promise of DB-1310: A HER3-Targeting Antibody-Drug Conjugate in Advanced Solid Tumors
News Publication Date: 2025
Web References:
https://meetings.asco.org/2025-asco-annual-meeting/16353?presentation=244179#244179
https://www.uclahealth.org/cancer
https://www.uclahealth.org/providers/aaron-lisberg
Keywords: Cancer; Lung cancer; Antibody therapy; Clinical studies; Clinical trials; Drug studies
Tags: advanced non-small cell lung cancerantibody-drug conjugatecancer receptor overexpressioncytotoxic chemotherapy payloadDB-1310 clinical trialHER3-targeted therapyinnovative cancer treatmentsprecision oncology advancementssystemic toxicity reductiontargeted cancer therapeuticstreatment-resistant solid tumorsUCLA Jonsson Comprehensive Cancer Center