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Non Small Cell Lung CarcinomaPhase 1MK3475-223NCT02938624

Anti PD-1 Neo-adjuvant Treatment for NSCLC

A Phase 1 study testing Pembrolizumab 200 mg IV single dose, Pembrolizumab 200 mg IV twice interval 21 days and Pembrolizumab 200 mg IV Twice interval 21d,surgery after 10d in people with Non Small Cell Lung Carcinoma and Stage I, run by Jair Bar, M.D., Ph.D. at 1 site in Israel.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

A single arm, phase I, dose escalation trial and expansion cohort, examining the safety and feasibility of neoadjuvant pembrolizumab treatment for early resectable NSCLC patients. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Non Small Cell Lung Carcinoma, Stage I, Stage II
What is being tested?
Pembrolizumab 200 mg IV single dose, Pembrolizumab 200 mg IV twice interval 21 days and Pembrolizumab 200 mg IV Twice interval 21d,surgery after 10d
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteIsrael
Study dates
7 Jan 2017to Aug 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Clinical or pathological diagnosis of early resectable NSCLC stage I-II (AJCC version 7).
  • Have measurable tumor of a least one cm in its largest diameter.
  • Clinically assessed to be a candidate for curative intent lobectomy or larger procedure (e.g. bilobectomy, pneumonectomy, lobectomy with segmentectomy, etc).
  • Is willing to undergo a procedure aimed to collect tumor tissue for pathologic diagnosis and for research correlative studies.
  • Be willing and able to provide written informed consent/assent for the trial.
  • Be > 18 years of age on day of signing informed consent.
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  • Have a performance status of 0 or 1 on the ECOG Performance Scale.
  • Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
  • Table 1: Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC) >=1,500 /mcL Platelets>=100,000 / mcL Hemoglobin>= 9 g/dL or >=5.6 mmol/L RenalSerum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) <=1.5 X upper limit of normal (ULN) OR >=60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Hepatic Serum total bilirubin <=1.5 X ULN OR Direct bilirubin <= ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) <= 2.5 X ULN OR Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants <=1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants aCreatinine clearance should be calculated per institutional standard.
  • 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.
  • 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.
  • 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.

Who cannot join

  • Severe lung emphysema with a significantly elevated risk of dangerous complications from a biopsy of a lung lesion.
  • Predicted post-operative (PPO)-FEV1 or PPO-DLCO < 30% (as calculated based on patient's age, sex, weight, height and planned operation).
  • Has a known 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.
  • Has had a prior monoclonal antibody 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.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy (besides as part of a curative treatment for a different malignancy, completed 5 years or more prior recruitment to study).
  • Has a known additional active malignancy. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, low grade bladder TCC or in situ cervical cancer that has undergone potentially curative therapy. History of other malignancies can be permitted provided at least five years have passed since the completion of a potentially curative therapy.
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  • Has 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. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has 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.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is 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.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment.

Trial locations and contacts

1 site in 1 country.

Israel1 site

  • Sheba Medical Center

    Ramat Gan, 52621

Other trials in Israel

About this study

Official title: Anti PD-1 Neo-adjuvant Treatment for Early Stage NSCLC - Phase I Study

A single arm, phase I, dose escalation trial and expansion cohort, examining the safety and feasibility of neoadjuvant pembrolizumab treatment for early resectable NSCLC patients.

Hypothesis: The investigators hypothesize that response rate to neo-adjuvant pembrolizumab will be higher than the response rate of advanced NSCLC patients.

Read the detailed description

16-28 patients with apparently operable NSCLC, clinically staged I-II with a resectable tumor would be recruited. Recruitment would be based on clinical assessment by a qualified Thoracic surgeon, with the appreciation that some of the recruited patients would eventually be deemed to be non-operable, or with a non-resectable disease, or to harbor a diagnosis different from NSCLC.

Screen of consenting patients would include a diagnostic biopsy that includes core needle biopsy procedure. Fresh as well as formalin fixed paraffin embedded baseline tumor samples will be obtained according to common Standard Operating Procedures. Specimens would be processed as per pathology standard of care and two cores or more will be utilized later for the research study.

A patient recruited after a previous diagnostic biopsy, would be eligible for the trial only if willing to undergo a repeat diagnostic procedure as above. Processing of biopsy material will be similar regardless if it is first or second biopsy.

Trial treatment will commence only following pathological confirmation of NSCLC, complete staging including CT-PET and brain imaging, and positive pre-op cardiac and pulmonary assessment.

Study schedule Dose levels of this study are defined by dose of drug as well as number of treatments and required interval from last treatment to surgery. At least 3 subjects in a dose cohort must complete the dose limiting toxicity (DLT) evaluation period before dosing is initiated at the next higher dose level. Only toxicities occurring during the DLT period will be considered as DLTs and utilized to inform dose escalation decisions. The DLT period starts with the first dose of pembrolizumab till 30 days post-surgery.

Cohorts consists of 3-6 subjects per dose level, to be treated with study therapy following a 3+3 schema.

Dose escalation will proceed between cohorts according to a modified "3+3 design," as explained in the following scheme. Dose-limiting toxicity (DLT) is defined below and is confined in time as defined above. As a safety feature, a new dosing/schedule level will open only after the end of 30 post-operative days of the last patient in the previous cohort. If cohort one will be found to be too high as RP2D/schedule, the next patients will be treated at a dose/schedule level minus one. Only one step of dose reduction is planned.

Being tested
Pembrolizumab 200 mg IV single dose, Pembrolizumab 200 mg IV twice interval 21 days, Pembrolizumab 200 mg IV Twice interval 21d,surgery after 10d, Pembrolizumab 100 mg I.V single dose, Surgical resection of tumor
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pembrolizumab 200 mg IV single doseDrug

    Also called keytruda

    Pembrolizumab 200 mg IV single dose, 21 days later surgery

  • Pembrolizumab 200 mg IV twice interval 21 daysDrug

    Also called keytruda

    Pembrolizumab 200 mg IV twice interval 21 days, 21 days later surgery

  • Pembrolizumab 200 mg IV Twice interval 21d,surgery after 10dDrug

    Also called keytruda

    Pembrolizumab 200 mg IV Twice interval 21d,surgery after 10d

  • Pembrolizumab 100 mg I.V single doseDrug

    Also called keytruda

    Pembrolizumab 100 mg I.V single dose, surgery after 21 days.

  • Surgical resection of tumorProcedure or surgery

    Also called Lobectomy/pneumonectomy/bi-lobectomy

    Surgical resection of tumor by any of the acceptable procedures

Study groups in NCT02938624
Study groupRoleWhat they receive
cohort1ExperimentalPembrolizumab 200 mg I.V single dose
Receives: Drug: Pembrolizumab 200 mg IV single dose; Procedure: Surgical resection of tumor
Cohort IIExperimentalPembrolizumab 200 mg I.V Twice interval 21 days
Receives: Drug: Pembrolizumab 200 mg IV twice interval 21 days; Procedure: Surgical resection of tumor
Cohort IIIExperimentalPembrolizumab 200 mg IV Twice interval 21d,surgery after 10d
Receives: Drug: Pembrolizumab 200 mg IV Twice interval 21d,surgery after 10d; Procedure: Surgical resection of tumor
COHORT -1ExperimentalPembrolizumab 100 mg I.V single dose
Receives: Drug: Pembrolizumab 100 mg I.V single dose; Procedure: Surgical resection of tumor

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicities

    Protocol defined dose limiting toxicities, aiming to identify RP2D=Recommended Phase 2 Dose/schedule.

    Measured: 24 months

  2. Percentage of residual viable tumor cells

    Percent residual viable tumor cells in post-treatment pathologic specimen

    Measured: 24 months

  3. Percent change in tumor volume

    Volumetric CT assessment at CT scan performed prior to surgical resection of tumor, relative to base line CT scan.

    Measured: 24 months

Secondary outcomes (2)

  1. Median time-to-recurrence.

    Median time-to-recurrence of disease in NSCLC patients treated with neo-adjuvant pembrolizmab and surgical resection of tumor, assessed by Kaplan-Meier method.

    Measured: 48 Months

  2. Median Overall survival.

    Median Overall survival of NSCLC patients treated with neo-adjuvant pembrolizmab and surgical resection of tumor, assessed by Kaplan-Meier method.

    Measured: 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2016 (estimated)
  2. Study start7 Jan 2017
  3. Primary completionAug 2021
  4. Study completionAug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02938624
Sponsor's protocol ID
3282/16SMC
Acronym
MK3475-223
Status last verified
Dec 2021
First submitted
12 Oct 2016
Last updated
14 Dec 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pembrolizumab 200 mg IV single dose, Pembrolizumab 200 mg IV twice interval 21 days and Pembrolizumab 200 mg IV Twice interval 21d,surgery after 10d in people with Non Small Cell Lung Carcinoma and Stage I, run by Jair Bar, M.D., Ph.D. at 1 site in Israel.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicities (time frame: 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02938624.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2021.

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