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

Not Applicable

Active, not recruiting

• Conditions: Head and Neck Squamous Cell Carcinoma; Non Small Cell Lung Cancer; Melanoma
• Interventions: Procedure: Biopsy

• Registration Number: NCT03412058
• Lead Sponsor: UNICANCER

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-11-14
• Study First Submitted QC: 2018-01-25
• Study First Posted: 2018-01-26
• Study Start: 2018-06-27
• Primary Completion: 2024-01-02
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-01
• Last Update Posted: 2024-02-02
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 670

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Melanoma	Biopsy	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
HNSCC	Biopsy	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
NSCLC	Biopsy	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

Primary Outcome Measures

Name	Time	Method
Sensitivity of response signature	84 days	The sensitivity is defined as the ratio of patients classified as responder by the signature to the number of patients presenting an objective response (CR or PR) according to centralized assessment of RECIST v1.1.

Secondary Outcome Measures

Name	Time	Method
Treatment costs	5 years	including cost of antiPD-1/PD-L1 treatment and supportive care for antiPD-1/PD-L1 treatment-related adverse events
Progression-free survival	5 years	defined as the time from inclusion until documented disease progression (PD) according to RECIST v1.1, or death, whichever occurs first.
Overall survival	5 years	defined as the time from inclusion until death due to any cause.
Duration of response	5 years	defined as the time from first observation of objective response according to RECIST v.1.1 until PD or death, whichever occurs first
Tumour size	5 years	Changes in tumour size over time
Frequency and severity of adverse events occuring during the observation period	Through treatment period	Adverse events will be evaluated according to NCI-CTCAE v4
Objective response	84 days	Objective response as assessed centrally according to RECIST v1.1.
iProgression-free survival	5 years	defined as the time from inclusion until documented PD according to iRECIST or death, whichever occurs first.

Trial Locations

Locations (19)

Centre Hospitalier Inter. de Creteil; 🇫🇷 Créteil, France

Institut Bergonie; 🇫🇷 Bordeaux, France

Centre Oscar lambret; 🇫🇷 Lille, France

Centre Hospitalier de Caen; 🇫🇷 Caen, France

Centre Georges François Leclerc; 🇫🇷 Dijon, France

Centre Jean Perrin; 🇫🇷 Clermont-Ferrand, France

Centre Léon Bérard; 🇫🇷 Lyon, France

Institut Régional du Cancer de Montpellier; 🇫🇷 Montpellier, France

Institut de cancérologie de l'ouest; 🇫🇷 Nantes, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

Institut Curie; 🇫🇷 Paris, France

Institut Claudius Regaud - IUCT- 0; 🇫🇷 Toulouse, France

Institut Jean Godinot; 🇫🇷 Reims, France

CHU Saint-Etienne, Hôpital Nord; 🇫🇷 Saint-Étienne, France

Gustave Roussy; 🇫🇷 Villejuif, France

Centre Eugène Marquis; 🇫🇷 Rennes, France

CHU de Tours; 🇫🇷 Tours, France

Institut Curie - Hôpital René Huguenin; 🇫🇷 Saint-Cloud, France

Institut Cancérologie de Lorraine; 🇫🇷 Vandœuvre-lès-Nancy, France