IPH5201 and Durvalumab in Patients With Resectable Non-Small Cell Lung Cancer (MATISSE)

Phase 2

Recruiting

• Conditions: Non Small Cell Lung Cancer
• Interventions: Drug: IPH5201 + durvalumab + standard chemotherapy

• Registration Number: NCT05742607
• Lead Sponsor: Innate Pharma

Brief Summary

The study is intended to assess the safety and efficacy of neoadjuvant combination of IPH5201 and durvalumab in addition to standard chemotherapy and adjuvant combination of IPH5201 and durvalumab in untreated patients with resectable, early-stage (stage II to IIIA) non-small cell lung cancer (NSCLC).

Detailed Description

This is an open-label, single-arm multicenter study. Eligible patients will be enrolled and will receive IPH5201 + Durvalumab + standard of care chemotherapy before surgery followed by IPH5201 + Durvalumab post-surgery.

Study Timeline

• Study First Submitted: 2023-02-15
• Study First Submitted QC: 2023-02-23
• Study First Posted: 2023-02-24
• Study Start: 2023-06-23
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-16
• Primary Completion: 2025-06
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Newly diagnosed and previously untreated patients with histologically or cytologically documented NSCLC resectable (Stage IIA to Stage IIIA) disease (according to Version 8 of IASLC Staging Manual in Thoracic Oncology 2016.
2. WHO Performance Status or Eastern Cooperative Oncology Group of 0 or 1.
3. Adequate organ and marrow function.
4. Must have a life expectancy of at least 12 weeks.
5. Body weight > 35 kg.
6. Females of childbearing potential should use an acceptable method of contraception from the time of screening throughout the total duration of the study.
7. Negative pregnancy test (serum or urine) for women of childbearing potential.
8. Provision of tumor samples (newly acquired [preferred] or archival tumor tissue [≤ 6 months old]) to confirm Programmed Death-Ligand 1 status, Epidermal Growth Factor Receptor, or Anaplastic Lymphoma Kinase status.
9. Provision of tumor samples appropriate for exploratory biomarker analyses.
10. Patients will be suitable for inclusion if the planned surgery to be performed will be lobectomy, sleeve resection, or bilobectomy, as determined by the attending surgeon based on the baseline findings.
11. A pre- or post-bronchodilator FEV1 of 1.0 L and DLCO > 40% postoperative predicted value.

Exclusion Criteria

1. Participants with sensitising EGFR mutations or ALK translocations.
2. History of allogeneic organ transplantation.
3. Active or prior documented autoimmune or inflammatory disorders.
4. Uncontrolled intercurrent illness, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active ILD, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement.
5. History of any grade of venous or arterial thromboembolic events including cerebrovascular accident, transient ischemic attack, or unstable angina pectoris within 6 months prior to enrollment.
6. History of another primary malignancy.
7. Patients with small-cell lung cancer or mixed small-cell lung cancer.
8. History of active primary immunodeficiency.
9. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive HBsAg result) and HCV. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
10. Patients who have preoperative radiotherapy treatment as part of their care plan.
11. Patients who require or may require pneumonectomy, segmentectomies, or wedge resections, as assessed by their surgeon, to obtain potentially curative resection of primary tumor.
12. QTc interval ≥ 470 ms (NOTE: If prolonged, then 2 additional ECGs should be obtained and the average QTcF interval should be used to determine eligibility).
13. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
14. Any medical contraindication to treatment with chemotherapy as listed in the local labelling.
15. Patients with moderate or severe cardiovascular disease.
16. Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
17. Receipt of live attenuated vaccine within 30 days prior to the first dose of study interventions.
18. Major surgical procedure (as defined by the Investigator) within 30 days prior to the first dose of study drugs.
19. Prior exposure to immune-mediated therapy.
20. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drugs.
21. Participation in another clinical study with an investigational product administered within 30 days prior to enrolment.
22. Previous study drugs (durvalumab, IPH5201) assignment in the present study.
23. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of study drugs administration.
24. Involvement in the planning and/or conduct of the study (applies to both company staff and/or staff at the study site).
25. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
26. Exclusion criteria for participation in the optional (DNA) genetics research component.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IPH5201 + durvalumab + standard chemotherapy	IPH5201 + durvalumab + standard chemotherapy	Patients will receive Neoadjuvant therapy with IPH5201 and durvalumab in addition to standard chemotherapy. Following surgery, patients will receive adjuvant treatment with IPH5201 and durvalumab.

Primary Outcome Measures

Name	Time	Method
Pathological Complete Response (pCR)	16 weeks after the first dose of study intervention.	Number of patients with pathological Complete Response (pCR)
Adverse events (AEs) and serious adverse events (SAEs)	Until Day 90 after the last dose of study interventions.	Number of patients with adverse events (AEs) and serious adverse events (SAEs).

Secondary Outcome Measures

Name	Time	Method
Event-Free Survival (EFS)	Up to approximately 2 years.	Number of patients experiencing an Event-Free Survival (EFS) event.
Disease Free Survival (DFS)	Up to approximately 2 years.	Number of patients experiencing a Disease Free Survival (DFS) event (event from surgery onwards).
Surgical resection	Approximately 16 weeks after the first dose of study intervention.	Number of participants having surgical resection.
Major Pathological Response (mPR)	Approximately 16 weeks after the first dose of study intervention.	Number of patients with a major Pathological Response (mPR).
Objective Response Rate (ORR)	Up to approximately 4 months adjuvant.	Number of patients with an Objective Response Rate (ORR).
Overall Survival (OS)	Up to approximately 2 years.	Overall Survival (OS).
PK of IPH5201 in combination with durvalumab +/- chemotherapy	Up to approximately 4 months adjuvant.	Serum concentration (PK) of IPH5201 in combination with durvalumab +/- chemotherapy, in patients receiving neoadjuvant and adjuvant treatment.
Anti-study drug antibodies (ADA)	Up to approximately 4 months adjuvant.	Number of patients with anti-study drug antibodies (ADA).

Trial Locations

Locations (30)

University General Hospital of Patras; 🇬🇷 Patras, Greece

Charles Nicolle Hospital; 🇫🇷 Rouen, France

Pulmonology Institute Torokbalint; 🇭🇺 Torokbalint, Hungary

Veszprem County Pulmonology Institute; 🇭🇺 Farkasgyepu, Hungary

University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

St. Anthony's Hospital - BayCare Health System; 🇺🇸 Saint Petersburg, Florida, United States

CHU de Limoges; 🇫🇷 Limoges, France

Northwell Health Cancer Institute / Center for Novel Cancer Therapeutics; 🇺🇸 Lake Success, New York, United States

Angers University Hospital Center; 🇫🇷 Angers, France

Hospital Calmette; 🇫🇷 Lille, France

Koranyi National Institute of Pulmonology, 14th Department of Pulmonology; 🇭🇺 Budapest, Hungary

Petz Aladar University Teaching Hospital, Department of Pulmonology; 🇭🇺 Győr, Hungary

University Teaching Hospital in Bialystok, 2nd Department of Lung Diseases and Tuberculosis; 🇵🇱 Bialystok, Poland

University Hospital Center Caen; 🇫🇷 Caen, France

Marseille University Hospital Center - North Hospital; 🇫🇷 Marseille, France

Rennes University Hospital Center - Hospital Pontchaillou; 🇫🇷 Rennes, France

Gustave Roussy; 🇫🇷 Villejuif, France

H. Lee Moffitt Cancer Center & Research Institute; 🇺🇸 Tampa, Florida, United States

UW Carbone Cancer Center - Cancer Connect; 🇺🇸 Madison, Wisconsin, United States

Henry Dunant Hospital Center; 🇬🇷 Athens, Greece

University General Hospital "Attikon"; 🇬🇷 Athens, Greece

University General Hospital of Ioannina; 🇬🇷 Ioánnina, Greece

Jasz-Nagykun-Szolnok County Hetenyi Geza Hospital-Clinic, Department of Oncology; 🇭🇺 Szolnok, Hungary

Millennium Research & Clinical Development; 🇺🇸 Houston, Texas, United States

Leon Berard Center; 🇫🇷 Lyon, France

Eugenia and Janusz Zeyland Wielkopolskie Centre of Pulmonology and Thoracic Surgery; 🇵🇱 Poznań, Poland

Military Institute of Medicine - National Research Institute; 🇵🇱 Warsaw, Poland

Mandziuk Slawomir - Specialist Medical Practice; 🇵🇱 Lublin, Poland

Specialist Hospital in Prabuty Sp. z o.o. (LLC); 🇵🇱 Prabuty, Poland

John Paul II Specialist Hospital in Krakow; 🇵🇱 Krąków, Poland