2026-04-29
Localized lung cancer: a new triplet therapy shows promising signs of efficacy
Oncology
By Elodie Vaz | Published on April 29,
2026 | 4 min read
Presented during an oral session at the American Association for Cancer Research (AACR) congress held from April 17 to 22 by Prof. Fabrice Barlesi, the phase II MATISSE study brings new hope for the management of localized and operable non–small cell lung cancer (NSCLC). By adding an innovative molecule to the current standard combining chemotherapy and immunotherapy, this triplet strategy has shown encouraging early clinical results, particularly in certain patient subgroups.
Non–small cell lung cancers account for 85–90% of the more than 52,000 new lung cancer cases diagnosed each year in France. They represent the third most common cancer in women, the second in men, and remain the leading cause of cancer-related death in men. Over the past decade, the advent of immunotherapy has profoundly changed the prognosis of this disease. By stimulating the immune system to better recognize and destroy tumor cells, this approach has led to durable responses, including in metastatic disease.
In early, operable stages, the standard of care now relies on a so-called perioperative approach: a combination of chemotherapy and immunotherapy before surgery, followed by immunotherapy alone afterward. The goal is twofold: to reduce tumor size before surgery and to limit the risk of recurrence afterward.
This strategy has already demonstrated its effectiveness. The phase III AEGEAN trial, published in 2023, reported a pathological complete response rate (absence of viable cancer cells in the surgical specimen) of 17.2% with the chemotherapy/immunotherapy combination, compared with 4.3% with chemotherapy alone.
Despite these advances, a significant proportion of patients remain resistant to immunotherapy. It is in this context that the MATISSE study was designed. Its objective: to evaluate the benefit of adding IPH5201, a monoclonal antibody targeting CD39, an enzyme expressed in the tumor microenvironment of several cancers, including NSCLC. CD39 plays a key role in immune regulation. While it normally helps prevent excessive immune activation, tumors can exploit it to create an immunosuppressive environment, reducing local inflammation and limiting the effectiveness of immunotherapies. By inhibiting CD39, IPH5201 aims to restore a more inflammatory tumor microenvironment that may be more responsive to immunotherapy.
MATISSE is a single-arm phase II trial that included 40 patients with early-stage, operable NSCLC.
Before surgery, patients received a triplet therapy combining chemotherapy, durvalumab (an anti–PD-L1 antibody), and IPH5201. After surgery, durvalumab and IPH5201 were continued.
The presented data show that this triplet therapy has a favorable safety profile, with no new toxicity signals compared with the current standard. In terms of efficacy, the overall pathological complete response rate reached 27.5%, higher than that observed in AEGEAN, although indirect comparisons should be interpreted with caution.
Subgroup analysis highlights a correlation with PD-L1 expression, a predictive biomarker for response to immunotherapy:
As Prof. Fabrice Barlesi stated in a press release from the Gustave Roussy Institute: “The results of the MATISSE study are encouraging. They suggest the benefit of adding IPH5201 to the current standard treatment for early-stage, operable NSCLC. This triplet therapy showed promising pathological complete response rates at the time of surgery. In a small subgroup of patients whose tumors strongly express the PD-L1 marker, this rate even reached 50%. These initial findings now need to be confirmed in a larger number of patients through randomized comparative clinical trials.”
These results pave the way for potential personalized treatment intensification in localized NSCLC. It now remains to be confirmed in randomized trials whether this improvement in pathological complete response will translate into a lasting benefit in recurrence-free survival and overall survival.
Read next: CD146: friend or foe of the lung?
About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans
Presented during an oral session at the American Association for Cancer Research (AACR) congress held from April 17 to 22 by Prof. Fabrice Barlesi, the phase II MATISSE study brings new hope for the management of localized and operable non–small cell lung cancer (NSCLC). By adding an innovative molecule to the current standard combining chemotherapy and immunotherapy, this triplet strategy has shown encouraging early clinical results, particularly in certain patient subgroups.
A common disease with still poor prognosis
Non–small cell lung cancers account for 85–90% of the more than 52,000 new lung cancer cases diagnosed each year in France. They represent the third most common cancer in women, the second in men, and remain the leading cause of cancer-related death in men. Over the past decade, the advent of immunotherapy has profoundly changed the prognosis of this disease. By stimulating the immune system to better recognize and destroy tumor cells, this approach has led to durable responses, including in metastatic disease.
In early, operable stages, the standard of care now relies on a so-called perioperative approach: a combination of chemotherapy and immunotherapy before surgery, followed by immunotherapy alone afterward. The goal is twofold: to reduce tumor size before surgery and to limit the risk of recurrence afterward.
This strategy has already demonstrated its effectiveness. The phase III AEGEAN trial, published in 2023, reported a pathological complete response rate (absence of viable cancer cells in the surgical specimen) of 17.2% with the chemotherapy/immunotherapy combination, compared with 4.3% with chemotherapy alone.
The goal: overcoming resistance to immunotherapy
Despite these advances, a significant proportion of patients remain resistant to immunotherapy. It is in this context that the MATISSE study was designed. Its objective: to evaluate the benefit of adding IPH5201, a monoclonal antibody targeting CD39, an enzyme expressed in the tumor microenvironment of several cancers, including NSCLC. CD39 plays a key role in immune regulation. While it normally helps prevent excessive immune activation, tumors can exploit it to create an immunosuppressive environment, reducing local inflammation and limiting the effectiveness of immunotherapies. By inhibiting CD39, IPH5201 aims to restore a more inflammatory tumor microenvironment that may be more responsive to immunotherapy.
Assessing safety and efficacy
MATISSE is a single-arm phase II trial that included 40 patients with early-stage, operable NSCLC.
Before surgery, patients received a triplet therapy combining chemotherapy, durvalumab (an anti–PD-L1 antibody), and IPH5201. After surgery, durvalumab and IPH5201 were continued.
Promising results in PD-L1–positive patients
The presented data show that this triplet therapy has a favorable safety profile, with no new toxicity signals compared with the current standard. In terms of efficacy, the overall pathological complete response rate reached 27.5%, higher than that observed in AEGEAN, although indirect comparisons should be interpreted with caution.
Subgroup analysis highlights a correlation with PD-L1 expression, a predictive biomarker for response to immunotherapy:
- 35.7% pathological complete response in patients with PD-L1 expression ≥1% (n=28);
- 50% in those with expression ≥50% (n=14).
As Prof. Fabrice Barlesi stated in a press release from the Gustave Roussy Institute: “The results of the MATISSE study are encouraging. They suggest the benefit of adding IPH5201 to the current standard treatment for early-stage, operable NSCLC. This triplet therapy showed promising pathological complete response rates at the time of surgery. In a small subgroup of patients whose tumors strongly express the PD-L1 marker, this rate even reached 50%. These initial findings now need to be confirmed in a larger number of patients through randomized comparative clinical trials.”
These results pave the way for potential personalized treatment intensification in localized NSCLC. It now remains to be confirmed in randomized trials whether this improvement in pathological complete response will translate into a lasting benefit in recurrence-free survival and overall survival.
Read next: CD146: friend or foe of the lung?
About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans
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