Phase II, Single-arm Study of Adjuvant Pembrolizumab in N2 Positive Non-small Cell Lung Cancer Treated With Neoadjuvant Concurrent Chemoradiotherapy Followed by Curative Resection
Overview
- Phase
- Phase 2
- Intervention
- Paclitaxel
- Conditions
- Stage IIIA Non-small Cell Lung Cancer
- Sponsor
- Samsung Medical Center
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Efficacy of adjuvant pembrolizumab in N2 Positive NSCLC
- Last Updated
- 9 years ago
Overview
Brief Summary
This is a single arm, single center phase II study of adjuvant pembrolizumab in N2 positive non-small cell lung cancer (NSCLC) patients treated with neoadjuvant concurrent chemoradiotherapy followed by curative resection. Patients will receive pembrolizumab 200 mg every 3 weeks for up to 24 months.
The primary objective of this study is to assess the efficacy of adjuvant pembrolizumab treatment in terms of disease-free survival (DFS; per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by the investigator).
The baseline assessment is part of the screening procedures and should be performed within 0 to 14 days before the start of study drug. The imaging modalities used for RECIST 1.1 assessment will be CT of chest or PET-CT if indicated. Follow-up chest CT for all patients will be assessed every 12 weeks for the first year, every 16 weeks for the second year, every 6 months for the third year, and every year thereafter. In subjects who discontinued study therapy without documented recurrence, every effort should be made to continue monitoring their disease status.
If an unscheduled assessment is performed, and the patient has not progressed, every attempt should be made to perform the subsequent assessments at their scheduled visits. RECIST 1.1 scans will be analyzed by the investigator on site; a central review will not be conducted.
Following completion or discontinuation of study drug, patients will enter a follow-up period.
Once a patient has had objective relapse recorded and has discontinued study drug, the patient will be followed for survival status every 3 months until death, withdrawal of consent or the end of the study.
Patients will also be requested to provide tumor samples from diagnostic (obtained before neoadjuvant CCRT) and surgical specimens for exploratory biomarker study. Sample provision is not optional, subject to a specific consent.
Investigators
Myung-Ju Ahn
Professor
Samsung Medical Center
Eligibility Criteria
Inclusion Criteria
- •In order to be eligible for participation in this trial, the subject must:
- •Be willing and able to provide written informed consent for the trial
- •Be 18 years of age
- •Be within 6 weeks after complete resection after neoadjuvant CCRT
- •Have a performance status of 0 or 1 on the ECOG Performance Scale.
- •Patients who completed neoadjuvant CCRT regimen includes 5 cycles of weekly Paclitaxel (50 mg/m2 + 5DW200 MIV over 1hr) plus Cisplatin (25 mg/m2 + N/S 150 mL MIV over 1hr) concurrent with radiotherapy (44 Gy/22fx daily fraction).
- •Be willing to provide tissue from a obtained before neoadjuvant CCRT and surgical specimen (at least 10 slides from each surgically resected primary tumors and surgically resected metastatic lymph nodes)
- •Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 14 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 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
Exclusion Criteria
- •The subject must be excluded from participating in the trial if the subject:
- •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.
- •Participation in another clinical study with PD-1 or PD-L1 inhibitors at any time
- •Any previous treatment with a PD-1, PD-L1 inhibitor or any anti-cancer therapy after complete resection of lung cancer
- •Current or prior use of immunosuppressive medication within 28 days before the first dose of pembrolizumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
- •Mean QT interval corrected for heart rate (QTc) ≥470 ms using Bazett's correction
- •Has a known history of active TB (Bacillus Tuberculosis)
- •Active or prior documented inflammatory bowel disease (Crohn's disease or ulcerative colitis)
- •History of allogenic organ transplant
- •Hypersensitivity to pembrolizumab or any of its excipients.
Arms & Interventions
Pembrolizumab arm
Adjuvant Pembrolizumab
Intervention: Paclitaxel
Pembrolizumab arm
Adjuvant Pembrolizumab
Intervention: Pembrolizumab
Pembrolizumab arm
Adjuvant Pembrolizumab
Intervention: Curative resection
Pembrolizumab arm
Adjuvant Pembrolizumab
Intervention: Neoadjuvant concurrent chemoradiotherapy
Pembrolizumab arm
Adjuvant Pembrolizumab
Intervention: Cisplatin
Outcomes
Primary Outcomes
Efficacy of adjuvant pembrolizumab in N2 Positive NSCLC
Time Frame: 24 months
Disease free survival to evaluate the efficacy of adjuvant pembrolizumab in N2 positive non-small cell lung cancer patients treated with neoadjuvant concurrent chemoradiotherapy followed by curative resection.
Secondary Outcomes
- Overall survival (OS)(From date of radomization until the date of death from any cause, withdrawal of consent, or the end of the study, assessed up to 120 months)