Clinical trial NCT03412058: Identifying the Predictive Factors of Response to PD-1 or PD-L1 Antagonists
Official title: Prospective Cohort Study to Identify the Predictive Factors of Response to PD-1 or PD-L1 Antagonists
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Melanoma
Non Small Cell Lung Cancer
Head and Neck Squamous Cell Carcinoma
Keywords: PD-1
PD-L1
Lead sponsor: UNICANCER
Sponsor class: OTHER
Collaborators: name: Fondation ARC
First posted: 2018-01-26
Enrollment: 670
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Sensitivity of response signature
timeFrame: 84 days
Secondary outcomes:
measure: Frequency and severity of adverse events occuring during the observation period
timeFrame: Through treatment period
measure: Objective response
timeFrame: 84 days
measure: Objective response
timeFrame: 84 days
measure: Progression-free survival
timeFrame: 5 years
measure: iProgression-free survival
timeFrame: 5 years
measure: Overall survival
timeFrame: 5 years
measure: Duration of response
timeFrame: 5 years
measure: Treatment costs
timeFrame: 5 years
measure: Tumour size
timeFrame: 5 years
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre Hospitalier de Caen
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Créteil
country: France
facility: Centre Hospitalier Inter. de Creteil
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lille
country: France
facility: Centre Oscar lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Montpellier
country: France
facility: Institut Régional du Cancer de Montpellier
city: Nantes
country: France
facility: Institut de cancérologie de l'ouest
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie
city: Reims
country: France
facility: Institut Jean Godinot
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Saint-Cloud
country: France
facility: Institut Curie - Hôpital René Huguenin
city: Saint-Étienne
country: France
facility: CHU Saint-Etienne, Hôpital Nord
city: Toulouse
country: France
facility: Institut Claudius Regaud - IUCT- 0
city: Tours
country: France
facility: CHU de Tours
city: Vandœuvre-lès-Nancy
country: France
facility: Institut Cancérologie de Lorraine
city: Villejuif
country: France
facility: Gustave Roussy
Study officials:
affiliation: Centre Jean Perrin
name: Frédérique Penault-Llorca
role: PRINCIPAL_INVESTIGATOR
References: