Pembrolizumab re-challange as second or further line in patients with advanced non - small cell lung cancer MedDRA version: 20.0 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Keytruda
Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Powder and solvent for concentrate for solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number:
Sponsors
Spanish Long Cancer Group (SLCG/GECP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with hystologically or cythological confirmed NSCLC advanced or locally advanced disease not amenable to radical treatment (IIIA, IIIB, IV), squamous or non-squamous, recurrent after at least one prior line. - The subject must be willing and able to provide written informed consent/assent for the trial. - Patient must be aged = 18 years of age on day of signing informed consent. - Measurable disease (at least 1 lesion) based on RECIST 1.1. Patients will not be eligible if this lesion was irradiated before inclusion. - Documented prior benefit (Stable Disease, Partial Response, Complete Response) to check point PD1/PDL1 inhibitor (Nivolumab, Pembrolizumab, Darvolumab, Atezolizumab, Avelumab or others) for at least 16 weeks (Stable Disease, Partial Response, Complete Response) and progression while on treatment (or 12 weeks after stopping treatment (Cohort 2). No subsequent treatment before rechallenge is allowed in this cohort - Patient must be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. PDL1 must be evaluable and at least 1% positive in tumor tissue. - Have a performance status of 0-2 on the ECOG Performance Scale. - Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 7 days of treatment initiation. - 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 (Section 5.9.2) must be willing to use an adequate method of contraception as outlined in Section 5.9.2 – Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. - Male subjects of childbearing potential (Section 5.9.2) must agree to use an adequate method of contraception as outlined in Section 5.9.2- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
Exclusion criteria: Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 2. Has a 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. 3. Has a known history of active TB (Bacillus Tuberculosis) 4. Hypersensitivity to pembrolizuma(Bacillus Tuberculosis)b or any of its excipients. 5. Has 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. 6. Has 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 subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 7. Has 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. 8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids at a dose over 10 mg of prednisone or equivalent, for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 9. 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. 10. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 11. Has an active infection requiring systemic therapy. 12. Documented EGFR sensitizing mutation. 13. Documented ALK translocation. 14. 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. 15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 16. 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. 17. Has a known histo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of Pembrolizumab re-challenge administered 200 mg iv every 21 days in second or further line for advanced NSCLC after progression to monotherapy check point PD1 / PDL1 inhibitors measured by Overall Response Rate (ORR) per RECIST v1.1 and per modified RECIST (irRC).;Timepoint(s) of evaluation of this end point: 2 years recruiting patients 2 years of treatment with Pembrolizumab (MK-3475) At least 1 year of follow up;Secondary Objective: To evaluate the efficacy of Pembrolizumab re-challenge administered 200 mg iv every 21 days in second or further line for advanced NSCLC after progression to monotherapy check point PD1 / PDL1 inhibitors measured by Progression Free Survival (PFS) per RECIST v1.1 and per modified RECIST. and Overall Survival (OS). To evaluate the safety and tolerability profile of Pembrolizumab re-challange administered 200 mg iv every 21 days in second or further line for advanced NSCLC after progression to monotherapy check point PD1 / PDL1 inhibitors measured by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 ( U.S. Department of Health and Human Services - National Cancer Institute - National Institutes of Health );Primary end point(s): To evaluate the efficacy of Pembrolizumab re-challenge administered 200 mg iv every 21 days in second or further line for advanced NSCLC after progression to monotherapy check point PD1 / PDL1 inhibitors measured by Overall Response Rate (ORR) per RECIST v1.1 and per modified RECIST (irRC). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate the efficacy of Pembrolizumab re-challenge administered 200 mg iv every 21 days in second or further line for advanced NSCLC after progression to monotherapy check point PD1 / PDL1 inhibitors measured by Progression Free Survival (PFS) per RECIST v1.1 and per modified RECIST. and Overall Survival (OS). To evaluate the safety and tolerability profile of Pembrolizumab re-challange administered 200 mg iv every 21 days in second or further line for advanced NSCLC after progression to monotherapy check point PD1 / PDL1 inhibitors measured by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 ( U.S. Department of Health and Human Services - National Cancer Institute - National Institutes of Health );Timepoint(s) of evaluation of this end point: 2 years recruiting patients 2 years of treatment with Pembrolizumab (MK-3475) At least 1 year of follow up | — |
Countries
Spain
Contacts
Public ContactEva Pereira
Spanish Lung Cancer Group (SLCG/GECP)
Outcome results
None listed