The 2024 European Society for Medical Oncology Asia Congress (ESMO Asia 2024) was recently held in Singapore, where the DESTINY-Gastric06 (DG06) trial presented its latest findings, sparking widespread discussion. We had the opportunity to speak with Dr. Zhi Peng from Beijing Cancer Hospital, one of the study’s authors, who shared insights on the latest results of DG06 and the role of antibody-drug conjugates (ADCs) in cancer treatment.

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Oncology Frontier: You presented the findings of the DESTINY-Gastric06 study at the congress. Could you introduce the background of the study and its key results?

Dr. Zhi Peng: The DESTINY-Gastric06 study is a single-arm, Phase II trial conducted in a Chinese patient population, primarily assessing objective response rate (ORR) as evaluated by independent central review (ICR) based on RECIST v1.1 criteria. This trial evaluated the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with advanced HER2-positive gastric cancer. Based on the study’s findings, China has now approved T-DXd for the late-line treatment of HER2-positive advanced gastric cancer patients.

Analyzing the trial data, a total of 73 patients with centrally confirmed HER2-positive gastric cancer were enrolled. The ICR-assessed ORR was 28.8%, while the investigator-assessed ORR was 37%. The median progression-free survival (PFS) was 5.7 months, and the median overall survival (OS) reached 12 months. Based on these results, China’s National Medical Products Administration (NMPA) approved trastuzumab deruxtecan for adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who had previously received at least two prior lines of therapy.

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Oncology Frontier: What are the safety concerns surrounding ADC therapies? How should clinicians recognize and manage ADC-related adverse effects?

Dr. Zhi Peng: ADC drugs represent a diverse category, and their safety profiles vary. Specifically, for DS-8201 (trastuzumab deruxtecan), data from the DESTINY-Gastric01 (DG01), DESTINY-Gastric02 (DG02), and our current DG06 trial suggest that its safety profile is manageable, with the main concern being hematologic toxicity.

In the DG06 trial, only three patients (3.2%) experienced interstitial lung disease (ILD), with two cases classified as Grade 1 and one case as Grade 2—all of which were effectively managed. While hematologic toxicity remains a notable risk, it is a common and controllable issue in oncology practice. Importantly, clinicians must implement tailored safety management strategies for each ADC to ensure patient safety.

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Oncology Frontier: How effective are ADC combination therapies for HER2-positive gastric cancer? Are there ongoing studies exploring this approach?

Dr. Zhi Peng: HER2-positive gastric cancer is one of the subtypes with the best response to targeted therapies. From the early days of trastuzumab monotherapy to chemotherapy combined with trastuzumab, and now the KEYNOTE-811 study incorporating pembrolizumab, treatment options have expanded significantly for these patients.

Currently, multiple late-line treatment options, including trastuzumab deruxtecan and vidutuxizumab, have been approved for HER2-positive gastric cancer. Additionally, several combination therapy strategies are being investigated. The DESTINY-Gastric03 study has laid the foundation for a global, multicenter trial called DESTINY-Gastric05, which will explore various ADC combination approaches. Vidutuxizumab is also being studied as a first-line treatment. A global multicenter clinical trial involving bispecific antibodies targeting HER2 has already begun patient enrollment.

Overall, targeting HER2 remains a dynamic area of research, with ongoing developments in monoclonal antibodies, bispecific antibodies, and ADCs, all being evaluated under different combination strategies.

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Oncology Frontier: ADC therapies are often described as a “smart” form of targeted treatment. Do you think ADCs will eventually replace traditional chemotherapy?

Dr. Zhi Peng: I don’t believe ADC therapies will completely replace chemotherapy for two key reasons. First, ADC therapies require a specific target, meaning their application is limited to patients with identifiable molecular markers. Second, their mechanisms differ from conventional chemotherapy, making them complementary rather than a full replacement.

For patients with actionable targets, ADCs could potentially replace chemotherapy in certain settings. Additionally, the biological mechanisms of ADCs continue to evolve. For example, TROP2-targeting ADCs have demonstrated efficacy regardless of TROP2 expression levels.

In conclusion, ADC therapies are an exciting and rapidly advancing field, but much remains to be explored regarding their optimal use, molecular targets, and combination strategies across different tumor types.