Among VHIO-led research that was selected by the American Society of Clinical Oncology (ASCO) to first outing during its 2022 Annual Meeting, 03 – 07 June, Chicago (IL, USA), two studies have reported promising antitumor activity of immune-based strategies for the treatment of previously untreated metastatic non-small cell lung carcinoma (NSCLC) and patients with relapsed small cell lung cancer (SCLC), respectively.
Potentiating immune-based therapies in combination
Updated results of the extended first-line NSCLC cohort of the TACTI-002 (Two ACTive Immunotherapy) multicenter two-stage phase II trial were presented by Enriqueta Felip, Principal Investigator of VHIO’s Thoracic Tumors and Head & Neck Cancer during an ASCO 2022 Oral Abstract Session (1).
This open-label, single-arm study was designed to evaluate the efficacy of a combined treatment approach pairing anti-PD-1 monoclonal antibody, pembrolizumab, with eftilagimod alfa, a soluble LAG-3 protein that binds to a subset of MHC class II on antigen presenting cells (APCs).
“We hypothesized that the stimulation of the APCs and subsequent T cell recruitment with eftilagimod alpha could lead to superior antitumor responses than those observed with pembrolizumab alone,” says Enriqueta Felip, Head of the Thoracic Cancer Unit at the Vall d’Hebron University Hospital’s (HUVH) Medical Oncology Department, which is led by VHIO’s Director, Josep Tabernero.
Findings showed that the combination of pembrolizumab with eftilagimod alfa in patients with untreated metastatic NSCLC, unselected for PD-L1 expression, resulted in encouraging antitumor activity and a favorable safety without chemotherapy was observed. These promising results support further investigation of this combined treatment approach.
“Immune-based therapies are increasingly stepping up as powerful anti-cancer armory across several tumor types. Novel combinatorial strategies aimed at boosting their efficacy will spur the development of more potent anti-cancer medicines and ultimately improve treatment and survival outcomes for our patients,” concludes Enriqueta Felip, President of the Spanish Society of Medical Oncology (SEOM).
Efficacy and safety of single-agent lurbinectedin in patients with relapsed small cell lung cancer
Results of post hoc analysis exploring the efficacy and safety of single-agent lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with relapsed small cell lung cancer (SCLC) enrolled in the phase III randomized ATLANTIS study, were presented by Alejandro Navarro, a Medical Oncologist and Clinical Investigator of Enriqueta Felip’s group at VHIO and the Thoracic Cancer Unit at Vall d’Hebron (Vall d’Hebron Barcelona Hospital Campus).
Lurbinectedin had previously shown activity in patients with SCLC. Results of a phase II study that included 105 patients with SCLC, showed that lurbinectedin as second-line treatment achieved an overall response rate of 35% and a median survival of 10.3 months. Based on these data, this agent received accelerated approval in June 2020 from the U.S. Food and Drug Administration (FDA) as monotherapy in this setting, and is one of the recommended treatment options in the National Comprehensive Cancer Network (NCCN) guidelines for the second-line treatment of patients with SCLC.
The phase III randomized ATLANTIS clinical trial assessed the efficacy of lurbinectedin plus chemotherapy, doxorubicin, versus Investigator’s choice between CAV or topotecan as a control arm in second-line.
“While the data from this study failed to show improved overall survival from combined treatment compared with standard therapy, a better tolerability profile was observed,” says Alejandro Navarro.
Now, results of post hoc analysis presented during a Poster Session at the 2022 ASCO Annual Meeting (2), show data of 50 patients with metastatic SCLC with disease progression on or after one prior line with platinum-based chemotherapy. These patients completed 10 cycles of the lurbinectedin-doxorubicin combination and switched to lurbinectedin monotherapy. The investigators reported a notable improvement in this subgroup of patients with a median response of 20.7 months, and an acceptable tolerability with no new safety signals.
“Although this analysis was performed in a highly selected population, these results provide additional insights into cancer drug response in these patients,” concludes Alejandro Navarro, first author of this present study.
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