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.
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).
The study also provides
interesting translational data. Pharmacodynamic analyses show complete and
sustained saturation of CD39 in the blood, confirming target engagement. In
addition, responders initially had higher levels of CD39+ cells and intratumoral
CD8+ lymphocytes, suggesting potential biomarkers for patient selection.
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 
