Chemotherapy With Pembrolizumab Continuation After Progression to PD-1/L1 Inhibitors

Chemotherapy Plus Pembrolizumab After Progression With Previous PD-1/PD-L1 Inhibitors in Patients With Advanced Non-small Cell Lung Cancer: Placebo-controlled Randomized Phase II Study

After progression to previous PD-1/L1 inhibitors (pembrolizumab, nivolumab, or atezolizumab), physicians' choice chemotherapy plus pembolizumab (or placebo) will be administered (3 weeks per cycle) until disease progression or unacceptable toxicity.

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer Metastatic
• Intervention / Treatment: Drug: Pembrolizumab plus chemotherapy; Drug: Placebo plus chemotherapy

Detailed Description

Previous PD-1/PD-L1 inhibitors should be 2nd or 3rd line therapy for advanced NSCLC. There should be no systemic therapy after previous PD-1/PD-L1 therapy, before the enrollment to this study.

• Study Type: Interventional
• Enrollment (Anticipated): 98
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jong-Mu Sun; Phone Number: 822-3410-3459; Email: jongmu.sun@skku.edu

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Jong-Mu Sun
    • Contact: Jong-Mu Sun; Phone Number: 82234103459 82234103459; Email: jongmu.sun@skku.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male /female participants who are at least 20 years of age on the day of signing informed consent with histologically confirmed diagnosis of
2. Histologically confirmed non-small cell carcinoma
3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization.
4. Received one or two cytotoxic chemotherapy for advanced NSCLC including at least one platinum-doublet
5. Has received prior therapy with an anti-PD-1, anti-PD-L1 agents (monotherapy) and progression to last PD-1/PD-L1 inhibitors. The last PD-1/PD-L1 inhibitor should be administered 6 weeks before the study enrollment, and no other systemic therapy should be done between the interval.
6. At least one measurable lesion Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
7. Available data for PD-L1 IHC results (any of one tested by 22C3, SP263, or SP142) irrespective of expression level.
8. EGFR and ALK wild type

Exclusion Criteria:

1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to [randomization/allocation] (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

2. Has received prior systemic anti-cancer therapy including investigational agents within 3 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to [randomization /allocation].

   Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.

   Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.

3. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
4. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

5. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 3 weeks prior to the first dose of study treatment.

   Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.

6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
7. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, well differentiated thyroid carcinoma, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
8. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. Patients with oligo (≤5) brain metastasis with size less than 1cm can be enrolled without prior radiotherapy, if the tumors are regarded as asymptomatic and stable, based on follow-up brain MRIs checked intervals of at least 3 months. However, all patients with previously non-irradiated brain metastases should have brain MRI checked within 4 weeks before starting administration of study drugs.
9. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any PD-1/PD-L1 inhibitors.
10. 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.
11. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
12. Has an active infection requiring systemic therapy.
13. Has a known history of Human Immunodeficiency Virus (HIV)
14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
15. Has a known history of active TB (Bacillus Tuberculosis).
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab plus chemotherapy; Pembrolizumab (200 mg) plus chemotherapy (physicians' choice among docetaxel, pemetrexed, or vinorelbine) every 3 weeks	Drug: Pembrolizumab plus chemotherapy; Pembrolizumab plus chemotherapy; Other Names: Chemotherapy: one of docetaxel, pemetrexed, or vinorelbine
Active Comparator: Placebo plus chemotherapy; Placebo plus chemotherapy (physicians' choice among docetaxel, pemetrexed, or vinorelbine) every 3 weeks	Drug: Placebo plus chemotherapy; Placebo plus chemotherapy; Other Names: chemotherapy: one of docetaxel, pemetrexed, or vinorelbine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Time interval from enrollment to disease progression or death	up to 60 moths

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Partial reseponse is defined as a decrease by 30% or more in sums of longest diameter of measurable target lesions	up to 60 months
Overall survival (OS)	Time interval between enrollment to death of any cause	60 months
Toxicity by CTCAE	AEs graded using CTCAE (Version 4.0) criteria.	60 months

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Anticipated): November 1, 2020
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: July 26, 2018
• First Submitted That Met QC Criteria: August 30, 2018
• First Posted (Actual): September 4, 2018

Study Record Updates

• Last Update Posted (Actual): December 9, 2019
• Last Update Submitted That Met QC Criteria: December 5, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Docetaxel; Pembrolizumab; Vinorelbine; Pemetrexed
• Other Study ID Numbers: SMC 2018-07-044

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No