Dr. Pedro Rocha, medical oncologist at Vall d’Hebron University Hospital and researcher of VHIO’s Thoracic Tumors Group, has been awarded an IASLC (International Association for the Study of Lung Cancer) Young Investigator Grant to study how sex differences in the response to BiTE therapy in patients with SCLC are driven by distinct molecular and immunological profiles, which can be identified and leveraged to predict long-term responders. The grant was presented during the World Conference on Lung Cancer (WCLC 2025), held in Barcelona from September 6 to 9.
The overall goal of the project is to identify and characterize sex-specific biomarkers that predict long-term response to BiTE therapies in patients with SCLC.
Small cell lung cancer is a highly aggressive and metastatic disease responsible for approximately 200,000 deaths each year worldwide. Despite extensive research, only modest therapeutic advances have been made in the past 30 years, with the 5-year survival rate remaining below 7%. The addition of immune checkpoint inhibitors (ICIs) to chemotherapy has become the new standard of care for advanced-stage SCLC. However, this approach provides only a modest two-month improvement in median overall survival (from 10 to 12 months), benefiting only a minority of patients.
Sex differences in response to immunotherapy
Response to ICIs has been shown to differ between men and women. A systematic review and meta-analysis of more than 10,000 patients treated with ICIs revealed that the magnitude of benefit is sex dependent. Specifically, the study found that men consistently experienced greater relative survival benefits than women, regardless of cancer type, line of treatment, or drug administered. In addition, a recent longitudinal study in individuals assigned female at birth undergoing gender-affirming testosterone therapy (trans men) showed that testosterone may significantly influence immune cell behavior. These findings reinforce the existence of immunological differences between men and women and highlight the need for further research into sex-dependent variations in immune response to therapy.
What are BiTEs?
BiTEs (bispecific T-cell engagers) are a special type of antibody designed to simultaneously recognize two different proteins: on the one hand, they specifically bind tumor cells, and on the other, they activate T cells to attack the tumor.
Recently, results from the phase 1/2 DeLLphi 300 and 301 trials evaluating tarlatamab, a BiTE antibody, showed promising outcomes, leading to accelerated FDA approval for patients with SCLC. In a recent update, tarlatamab demonstrated unprecedented survival outcomes and intracranial activity in previously treated patients. Nevertheless, despite these encouraging findings, long-term benefits of BiTEs remain uncommon, and no predictive biomarkers have been identified to date.
This IASLC-funded project aims to identify biomarkers that can predict which patients are most likely to benefit from BiTE immunotherapy.
“In fact, a preliminary analysis of patients treated with BiTEs at Vall d’Hebron showed a higher prevalence of long-term responders among women. These observations suggest potentially significant differences in anti-tumor immune responses to BiTE therapy based on sex,” says Dr. Pedro Rocha.
“Based on these findings, we hypothesize that sex-based differences in response to BiTE therapy in patients with SCLC are driven by distinct molecular and immunological profiles, which can be identified and used to predict long-term responders. In our proposal, we aim to investigate baseline molecular subtypes and dynamic changes in immune responses between male and female patients treated with BiTEs. To this end, our biobank already contains plasma and PBMC samples from patients diagnosed with extensive-stage SCLC undergoing BiTE therapy. These findings can then be expanded and validated in a larger cohort, providing the foundation for more personalized and sex-specific therapeutic approaches in the future,” he concludes.
