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

Melanoma Clinical Trial

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Official title:

Prospective Cohort Study to Identify the Predictive Factors of Response to PD-1 or PD-L1 Antagonists

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03412058
• Other study ID #: UC-0108/1708
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 27, 2018
• Est. completion date: December 2025

Study information

• Verified date: February 2024
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 670
• Est. completion date: December 2025
• Est. primary completion date: January 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 10?/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.

Related Conditions & MeSH terms

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

Intervention

Procedure:
• Biopsy
To be performed prior to anti-PD1/PD-L1 treatment initiation
• Biopsy
To be performed after 42 (±3) days of anti-PD1 or PD-L1 treatment in consenting patients
• Biopsy
To be performed at disease progression if medically feasible

Locations

Country	Name	City	State
France	Institut Bergonie	Bordeaux
France	Centre Hospitalier de Caen	Caen
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Hospitalier Inter. de Creteil	Créteil
France	Centre Georges François Leclerc	Dijon
France	Centre Oscar lambret	Lille
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 Jean Godinot	Reims
France	Centre Eugène Marquis	Rennes
France	Institut Curie - Hôpital René Huguenin	Saint-Cloud
France	CHU Saint-Etienne, Hôpital Nord	Saint-Étienne
France	Institut Claudius Regaud - IUCT- 0	Toulouse
France	CHU de Tours	Tours
France	Institut Cancérologie de Lorraine	Vandœuvre-lès-Nancy
France	Gustave Roussy	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
UNICANCER	Fondation ARC

Country where clinical trial is conducted

France, 

Outcome

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