Circulating microRNAs to choose the IO strategy in PD-L1≥50% NSCLC patients: the Ark clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione IRCCS Istituto Nazionale Dei Tumori

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Neoplasms [C04]

Trial duration

11 Sep 2023 → ongoing

Decision date (initial)

2023-05-02

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2022-502253-34-00

WHO UTN

U0000-0000-0000

ClinicalTrials.gov

NCT00000000

ISRCTN

ISRCTN00000000

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess and compare the efficacy of ICI-CHT versus ICI-SA as a first-line treatment in patients with advanced PD-L1≥50% NSCLC without driver alterations characterized by MSC-H.

Secondary objectives 3

1. To show that a quantitative assessment of main immune cell populations in freshly isolated blood samples (all leukocytes, lymphocytes, monocytes, neutrophils, MDSCs, T, B, NK and NKT cells as well as specific subsets of these main lineages) can allow to identify significant associations with response, PFS and OS in the two arms of the trial.
2. To show that therapy with ICI-SA, compared to combination ICI-CHT has distinct impact on the peripheral immune profile as evaluated by longitudinal assessment of pre-therapy and on-therapy blood samples.
3. The set-up of a biobank for the collection of adequate biological specimens at baseline and during treatment (including plasma, PBMC and tissue biopsies) that would be deeply characterized in the present and further studies to better define the effects of the combination ICI-CHT versus ICI-SA.

Conditions and MedDRA coding

non-small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Diagnosis of NSCLC in stage IIIC/ IV
2. Do not have driver alterations (EGFR, ALK, ROS-1, or BRAF V600E mutation or other genomic aberration for which an approved targeted therapy is available).
3. PD-L1 ≥50% tumor as determined by immunohistochemistry with anti-PD-L1 antibody (DAKO 22C3).
4. Have not received prior systemic treatment for advanced NSCLC
5. Be willing and able to provide written informed consent/assent for the trial.
6. Be ≥18 years of age on day of signing informed consent
7. Have measurable disease based on RECIST criteria version 1.1. Measurable lesions situated in a previously irradiated area may be considered target lesions if progression has been demonstrated in such lesions.
8. Have a performance status of 0-1 on the ECOG Performance Scale.
9. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
10. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
11. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
12. No history of active malignancy requiring treatment
13. Demonstrate adequate organ function as defined in Table 2, all screening labs should be performed within 15 days of treatment initiation.

Exclusion criteria 20

1. Prior systemic therapy for the treatment of metastatic NSCLC. Participants who have received neoadjuvant or adjuvant chemotherapy are eligible if the neoadjuvant/adjuvant therapy was completed at least 6 months prior to the development of metastatic disease.
2. Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
3. Presence of driver sensitizing alteration for which target therapy is available in clinical practice.
4. PD-L1 expression has been assessed as "low" by pathology laboratory (PD-L1<50%)
5. Not characterized by High-MSC risk level according to central prescreening evaluation
6. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
7. Have a known history of active TB (Bacillus Tuberculosis)
8. Hypersensitivity to Pembrolizumab and/or chemptherapy or any of their excipients.
9. Have had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
10. Have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
11. Have a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
12. Have active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
13. Have a history of non-infectious pneumonitis that required steroids or has current pneumonitis.
14. Have an active infection requiring systemic therapy.
15. Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
16. Have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
17. Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
18. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
19. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
20. Received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease Control Rate (DCR)

Secondary endpoints 4

1. Progression-Free Survival (PFS)
2. Overall Survival (OS)
3. Overall Response Rate (ORR)
4. Response Duration (DoR)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione IRCCS Istituto Nazionale Dei Tumori

Sponsor organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Address

Via Giacomo Venezian 1

City

Milan

Postcode

20133

Country

Italy

Scientific contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

Clinical trial contact person

Public contact point

Organisation

Fondazione IRCCS Istituto Nazionale Dei Tumori

Contact name

pubblic relations office

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications