Anti PD-1 Neo-adjuvant Treatment for NSCLC

NCT02938624 | Completed Phase 1 DMC

• 1 other identifier: 3282/16SMC
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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

Conditions

Non Small Cell Lung Carcinoma; Stage I; Stage II

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicities

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

  24 months

• Percentage of residual viable tumor cells

  Percent residual viable tumor cells in post-treatment pathologic specimen

  24 months

• Percent change in tumor volume

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

  24 months

Secondary Outcomes (2)

• Median time-to-recurrence.

  48 Months

• Median Overall survival.

  60 months

Other Outcomes (1)

• Change in percentage of cells expressing PDL1 in tumors with treatment

  24 Months

Study Arms (4)

cohort1

EXPERIMENTAL

Pembrolizumab 200 mg I.V single dose

Drug: Pembrolizumab 200 mg IV single dose; Procedure: Surgical resection of tumor

Cohort II

EXPERIMENTAL

Pembrolizumab 200 mg I.V Twice interval 21 days

Drug: Pembrolizumab 200 mg IV twice interval 21 days; Procedure: Surgical resection of tumor

Cohort III

EXPERIMENTAL

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

Drug: Pembrolizumab 200 mg IV Twice interval 21d,surgery after 10d; Procedure: Surgical resection of tumor

COHORT -1

EXPERIMENTAL

Pembrolizumab 100 mg I.V single dose

Drug: Pembrolizumab 100 mg I.V single dose; Procedure: Surgical resection of tumor

Interventions

Pembrolizumab 200 mg IV single dose DRUG

Pembrolizumab 200 mg IV single dose, 21 days later surgery

Also known as: keytruda

cohort1

Pembrolizumab 200 mg IV twice interval 21 days DRUG

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

Also known as: keytruda

Cohort II

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

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

Also known as: keytruda

Cohort III

Pembrolizumab 100 mg I.V single dose DRUG

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

Also known as: keytruda

COHORT -1

Surgical resection of tumor PROCEDURE

Surgical resection of tumor by any of the acceptable procedures

Also known as: Lobectomy/pneumonectomy/bi-lobectomy

COHORT -1; Cohort II; Cohort III; cohort1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Jair Bar, M.D., Ph.D.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Sheba Medical Centre Jair, MD PHD

  Chaim Sheba Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director, Institute of Oncology

Study Record Dates

• First Submitted: October 12, 2016
• First Posted: October 19, 2016
• Study Start: January 7, 2017
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: December 14, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)