Editor’s Note :
The 2023 World Conference on Lung Cancer (WCLC), organized by the International Association for the Study of Lung Cancer (IASLC), took place in Singapore from September 9-12. Dr. Melissa L. Johnson from Northwestern University’s Feinberg School of Medicine presented pivotal findings on antibody-drug conjugates (ADC) for treating small cell lung cancer (SCLC). We had the privilege to interview Dr. Johnson during the conference. Here are the highlights:
Background :
B7-H3, an immune modulatory protein, is overexpressed in several tumor types including SCLC. 65% of SCLC patients show moderate to high B7-H3 expression. I-DXd (Ifinatamab Deruxtecan) is a novel B7-H3 directed ADC, enhancing selective tumor cell death, reducing systemic exposure. A Phase 1/2 clinical trial assessed I-DXd for advanced solid tumors. Results after a median follow-up of 11.7 months on SCLC patients, including response rate, progression-free survival (PFS), overall survival (OS), and B7-H3 expression-based response analysis, are presented.
Methods :
The subgroup analysis focused on the SCLC cohort from the first part of the Phase 1/2 study, which included heavily pretreated late-stage solid tumor patients without B7-H3 expression screening. The therapeutic and safety evaluation was based on a 4.8–16.0mg/kg dose of I-DXd.
Results :
As of January 31, 2023, 21 SCLC patients were available for safety, tumor remission, PFS, and OS assessment. Two are still under treatment. The majority of patients had undergone platinum-based chemotherapy and immunotherapy. 11 patients (52%) achieved an objective response, with a median duration of 5.9 months. The median PFS was 5.8 months, while the median OS was 9.9 months. No apparent trend between tumor response and B7-H3 expression intensity was observed, though further validation with a larger sample is needed.
Conclusion :
I-DXd demonstrates effective, durable therapeutic results and controllable toxicity in heavily pretreated SCLC patients. A Phase II study targeting second or third-line extensive-stage SCLC patients is ongoing.
In an interview at the 2023 WCLC conference, Dr. Melissa L. Johnson shares her insights:
1. Oncology frontier : Why isn’t there a correlation between the best overall response and B7-H3 expression intensity?
Dr. Johnson : We noticed B7-H3 expression and tried linking it to efficacy. It’s important to remember that all patients expressed some level of B7-H3; even a slight expression might be enough. The intensity might not necessarily lead to a better response.
2. Oncology frontier : Why choose B7-H3 as a target for refractory SCLC?
Dr. Johnson : Our study had 22 SCLC patients, part of a larger trial. We looked at several tumor types and found B7-H3 expression to be significantly high, questioning their potential response to B7-H3 directed ADCs. We focused on SCLC due to the elevated expression and observed positive therapeutic responses across tumor types.
3. Oncology Frontier: Any other notable ADC advancements?
Dr. Johnson: ADCs are a significant theme at this conference. There’s ongoing research to use ADCs as primary treatments, potentially replacing chemotherapy. More data is still needed, but the initial patient cohorts show promise.
4. Oncology frontier : Any other exciting advancements or advice for refractory SCLC?
Dr. Johnson : SCLC patients on chemotherapy and checkpoint inhibitors often face deteriorating conditions upon cessation of chemotherapy. The DLL3 CD3 bispecific drugs, which appear to trigger an immune response in SCLC differently and more effectively than checkpoint inhibitors, are exciting. My advice to refractory SCLC patients is to explore clinical trials. There’s much hope for SCLC treatments, and we need to keep exploring new therapeutic avenues.
