Identifying the Predictive Factors of Response to PD-1 or PD-L1 Antagonists (CHECK'UP)

• ClinicalTrials.gov Identifier: NCT03412058
• Recruitment Status: Recruiting
• First Posted: January 26, 2018
• Last Update Posted: August 27, 2018
• Sponsor: UNICANCER
• Collaborator: Fondation ARC
• Information provided by (Responsible Party): UNICANCER

Tracking Information

• First Submitted Date: November 14, 2017
• First Posted Date: January 26, 2018
• Last Update Posted Date: August 27, 2018
• Actual Study Start Date: June 27, 2018
• Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 25, 2018)

Sensitivity of response signature [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 25, 2018)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 RECIST and iRECIST criteria. 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 Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Other

Condition

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

Intervention

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

Study Arms

• Experimental: 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
  Interventions:

  • Procedure: Biopsy
  • Procedure: Biopsy
  • Procedure: Biopsy
• Experimental: 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
  Interventions:

  • Procedure: Biopsy
  • Procedure: Biopsy
  • Procedure: Biopsy
• Experimental: 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
  Interventions:

  • Procedure: Biopsy
  • Procedure: Biopsy
  • Procedure: Biopsy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 25, 2018): 670
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)

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 (Appendix 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 < 80x109/L, International Normalised Ratio (INR) > 1.5 or prothrombin time (PT) > 1.5x 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Daniel Couch; 0180501296; d-couch@unicancer.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT03412058
• Other Study ID Numbers: UC-0108/1708
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: UNICANCER
• Study Sponsor: UNICANCER
• Collaborators: Fondation ARC

Investigators

• Principal Investigator: Frédérique Penault-Llorca; Centre Jean Perrin

• PRS Account: UNICANCER
• Verification Date: August 2018