Identifying the Predictive Factors of Response to PD-1 or PD-L1 Antagonists

NCT ID: NCT03412058

Last Updated: 2025-02-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

670 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-27

Study Completion Date

2025-12-31

Brief Summary

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This is a prospective cohort study which aims to identify predictive factors of response to PD-1 and PD L1 antagonists authorised for use in France in treatment of melanoma, NSCLC, or HNSCC.

Detailed Description

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The study will include 670 patients with melanoma, NSCLC, or HNSCC who are set to receive treatment with a single-agent PD-1 or PD L1 antagonist regimen as indicated in the respective European MA or under the conditions of a TAU and according to the standard practices at the investigational site.

Included patients will be followed for a total of 5 years. Prior to initiation of PD-1 or PD-L1 antagonist therapy, included patients will undergo a biopsy of a tumour lesion (unless suitable archived material is available) and provide a blood sample for immunohistochemistry and genomic studies. Patients at selected participating sites will also be asked to provide stool and saliva samples (optional). Additional optional biopsy samples may be collected from consenting patients after 42 (±3) days of PD-1 or PD-L1 antagonist treatment and in the event of disease progression or recurrence. Additional blood samples will also be collected at regular intervals throughout the observation period until disease progression, regardless of whether PD-1 or PD-L1 antagonist treatment is ongoing or has discontinued. Efficacy of treatment will be evaluated using both Response Evaluation Criteria in Solid Tumours (RECIST) and immune-related RECIST (iRECIST). Information regarding the PD-1 or PD-L1 antagonist related toxicities, subsequent antineoplastic treatments, and survival status will also be collected during the trial.

An elastic-net approach will be used to identify correlations between different parameters and develop a signature of response to treatment. For each indication, the patients will be separated into two cohorts: a 'training' cohort and a 'validation' cohort. The 'training' cohort will be made up of the first patients included in the indication and will be used to develop a predictive response score. The 'validation' cohort will include all the remaining patients. The performance of the predictive score will be tested in this second cohort.

Conditions

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Melanoma Non Small Cell Lung Cancer Head and Neck Squamous Cell Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Melanoma

Biopsy and blood samples will be collected from patients treated with an antiPD-1 or antiPD-L1 antibody with marketing authorization for the indication, during the course of their treatment

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

To be performed prior to anti-PD1/PD-L1 treatment initiation

Biopsy

Intervention Type PROCEDURE

To be performed after 42 (±3) days of anti-PD1 or PD-L1 treatment in consenting patients

Biopsy

Intervention Type PROCEDURE

To be performed at disease progression if medically feasible

NSCLC

Biopsy and blood samples will be collected from patients treated with an antiPD-1 or antiPD-L1 antibody with marketing authorization for the indication, during the course of their treatment

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

To be performed prior to anti-PD1/PD-L1 treatment initiation

Biopsy

Intervention Type PROCEDURE

To be performed after 42 (±3) days of anti-PD1 or PD-L1 treatment in consenting patients

Biopsy

Intervention Type PROCEDURE

To be performed at disease progression if medically feasible

HNSCC

Biopsy and blood samples will be collected from patients treated with an antiPD-1 or antiPD-L1 antibody with marketing authorization for the indication, during the course of their treatment

Group Type EXPERIMENTAL

Biopsy

Intervention Type PROCEDURE

To be performed prior to anti-PD1/PD-L1 treatment initiation

Biopsy

Intervention Type PROCEDURE

To be performed after 42 (±3) days of anti-PD1 or PD-L1 treatment in consenting patients

Biopsy

Intervention Type PROCEDURE

To be performed at disease progression if medically feasible

Interventions

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Biopsy

To be performed prior to anti-PD1/PD-L1 treatment initiation

Intervention Type PROCEDURE

Biopsy

To be performed after 42 (±3) days of anti-PD1 or PD-L1 treatment in consenting patients

Intervention Type PROCEDURE

Biopsy

To be performed at disease progression if medically feasible

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

1. Age ≥18 years old.
2. Histological confirmed diagnosis of one of the following:

* Non-resectable (stage III) or metastatic (stage IV) melanoma,
* Metastatic, EGFR- and ALK-negative, non-small cell lung cancer with a high level of PD-L1 expression (defined as a "tumour proportion score" of greater than or equal to 50%) which has not been previously treated with chemotherapy in the metastatic setting,
* Head and Neck squamous cell carcinoma that is that is recurrent or progressing following reference chemotherapy and that is not amenable to surgery or radiation therapy.
3. Indicated for treatment with a PD-1 or PD-L1 antagonist according to the European Marketing Authorisation or the conditions of a Temporary Authorisation of Use.
4. Estimated life expectancy ≥16 weeks.
5. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2.
6. Presence of at least one tumour lesion (except bone lesions) accessible to biopsy, if a biopsy is required (see below).
7. Willing and able to provide a pre-treatment biopsy sample, if a biopsy is required.

Note: where an archived tumour sample is available, this archived sample can be used in place of a fresh biopsy sample, if the patient has not received any antineoplastic therapy since the collection date.
8. Measurable disease according to RECIST v1.1 (Eisenhauer, 2009).
9. Beneficiary of social insurance coverage.
10. Comprehension of French.
11. Provision of written informed consent (signed and dated) prior to the initiation of any protocol specific procedure.

Exclusion Criteria

1. Any contraindication to treatment with a PD-1 or PD-L1 antagonist.
2. Any contraindication to a biopsy including: platelets \<80 x 10⁹/L, International Normalised Ratio (INR) \>1.5 or prothrombin time (PT) \>1.5 x upper limit of normal range (ULN), prolonged partial thromboplastin time (PTT) in the absence of factor XII deficiency or antiphospholipid antibodies, ongoing treatment with anticoagulants.
3. Bone metastasis as the only disease site available for biopsy.
4. Previous treatment with a PD-1 or PD-L1 antagonist.
5. Individuals deprived of liberty or placed under the authority of a tutor.
6. Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondation ARC

OTHER

Sponsor Role collaborator

UNICANCER

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Frédérique Penault-Llorca

Role: PRINCIPAL_INVESTIGATOR

Centre Jean Perrin

Locations

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Institut Bergonie

Bordeaux, , France

Site Status

Centre Hospitalier de Caen

Caen, , France

Site Status

Centre Jean Perrin

Clermont-Ferrand, , France

Site Status

Centre Hospitalier Inter. de Creteil

Créteil, , France

Site Status

Centre Georges François Leclerc

Dijon, , France

Site Status

Centre Oscar lambret

Lille, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Institut Régional du Cancer de Montpellier

Montpellier, , France

Site Status

Institut de cancérologie de l'ouest

Nantes, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

Institut Curie

Paris, , France

Site Status

Institut Jean Godinot

Reims, , France

Site Status

Centre Eugène Marquis

Rennes, , France

Site Status

Institut Curie - Hôpital René Huguenin

Saint-Cloud, , France

Site Status

CHU Saint-Etienne, Hôpital Nord

Saint-Etienne, , France

Site Status

Institut Claudius Regaud - IUCT- 0

Toulouse, , France

Site Status

CHU de Tours

Tours, , France

Site Status

Institut Cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

Site Status

Gustave Roussy

Villejuif, , France

Site Status

Countries

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France

Other Identifiers

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UC-0108/1708

Identifier Type: -

Identifier Source: org_study_id

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