Ignite Creation Date:
2025-12-24 @ 5:37 PM
Ignite Modification Date:
2026-02-20 @ 6:39 PM
Study NCT ID:
NCT03003468
Status:
COMPLETED
Last Update Posted:
2024-08-13
First Post:
2016-12-22
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Pembrolizumab + Imprime PGG for Metastatic Non-small Cell Lung Cancer After Progression on First-Line Therapy: Big Ten Cancer Research Consortium BTCRC-LUN15-017
Sponsor:
Lawrence Feldman, MD
Organization:
Study Overview
Official Title:
A Phase Ib/II Study of Anti-PD-1 Antibody Pembrolizumab and Imprime PGG for Patients With Metastatic Non-small Cell Lung Cancer After Progression on First-Line Therapy: Big Ten Cancer Research Consortium BTCRC-LUN15-017
Status:
COMPLETED
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is an open label, multi-institutional, single arm study with a dose escalation phase Ib cohort, followed by a phase II cohort of pembrolizumab and Imprime PGG. No randomization or blinding is involved.
Detailed Description:
OUTLINE: This is a multi-center study.
The phase Ib dose escalation will evaluate the combination of pembrolizumab and Imprime PGG for subjects with metastatic non-small cell lung cancer (NSCLC) after progression on first-line platinum-based chemotherapy. The phase II trial will test whether addition of Imprime PGG to pembrolizumab will increase median progression-free survival (PFS) in second line therapy setting in NSCLC.
PHASE Ib DOSE ESCALATION INVESTIGATIONAL TREATMENT:
Cohort 1 will consist of 3-6 patients who will receive
* Imprime PGG 2 mg/kg IV on Days 1, 8, 15 for Cycles 1-4
* Imprime PGG 2 mb/kg IV on Day 1 for Cycles 5-16
* Pembrolizumab 200 mg IV on Day 1 (cycle = 21 days)
Cohort 2 will consist of 3-6 patients who will receive
* Imprime PGG 4 mg/kg IV on Days 1, 8, 15 for Cycles 1-4
* Imprime PGG 2 mb/kg IV on Day 1 for Cycles 5-16
* Pembrolizumab 200 mg IV on Day 1 (cycle = 21 days)
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional three subjects will be enrolled at dose level 2. If all subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled into dose level 2 to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
PHASE II INVESTIGATIONAL TREATMENT:
Pembrolizumab will be given on Day 1 of each 21 day cycle after Imprime PGG, and the RP2D dose of Imprime PGG will be given on Days 1, 8 and 15 of each 21 day cycle. Treatment will continue up to 16 cycles, or until disease progression, unacceptable toxicity, subject refusal, or subject death either from progression of disease, the therapy itself, or from other causes.
Life expectancy: of 6 months or greater
The following baseline labs must be completed within 28 days prior to registration for protocol therapy:
Hepatic:
* total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 x ULN (except subject with Gilbert's Syndrome, who can have total bilirubin \< 3.0 mg/dl)
* aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
* alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
Renal:
* Serum creatinine ≤ 3 mg/dL OR
* if serum creatinine \> 3mg/dL, estimated glomerular filtration rate (GFR) ≥ 20 mL/min
Hematopoietic:
* hemoglobin ≥ 9 g/dL, subjects requiring transfusion will not be eligible to start study
* and absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L
* and platelet count ≥ 100 × 10\^9/L
Coagulation:
* INR \< 1.5 × ULN OR
* for subjects receiving anticoagulant, the subjects must, in the investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for subjects on warfarin should be in the therapeutic range. Low molecular weight heparin (LMWH) is allowed.
The phase Ib dose escalation will evaluate the combination of pembrolizumab and Imprime PGG for subjects with metastatic non-small cell lung cancer (NSCLC) after progression on first-line platinum-based chemotherapy. The phase II trial will test whether addition of Imprime PGG to pembrolizumab will increase median progression-free survival (PFS) in second line therapy setting in NSCLC.
PHASE Ib DOSE ESCALATION INVESTIGATIONAL TREATMENT:
Cohort 1 will consist of 3-6 patients who will receive
* Imprime PGG 2 mg/kg IV on Days 1, 8, 15 for Cycles 1-4
* Imprime PGG 2 mb/kg IV on Day 1 for Cycles 5-16
* Pembrolizumab 200 mg IV on Day 1 (cycle = 21 days)
Cohort 2 will consist of 3-6 patients who will receive
* Imprime PGG 4 mg/kg IV on Days 1, 8, 15 for Cycles 1-4
* Imprime PGG 2 mb/kg IV on Day 1 for Cycles 5-16
* Pembrolizumab 200 mg IV on Day 1 (cycle = 21 days)
If none of the 3 subjects experience a dose limiting toxicity (DLT) during the first cycle of therapy, an additional three subjects will be enrolled at dose level 2. If all subjects in dose level 2 complete the first cycle of therapy without DLT, 3 more subjects will be enrolled into dose level 2 to ensure only 0-1 of 6 subjects have a DLT. There will be no further escalation beyond dose level 2.
PHASE II INVESTIGATIONAL TREATMENT:
Pembrolizumab will be given on Day 1 of each 21 day cycle after Imprime PGG, and the RP2D dose of Imprime PGG will be given on Days 1, 8 and 15 of each 21 day cycle. Treatment will continue up to 16 cycles, or until disease progression, unacceptable toxicity, subject refusal, or subject death either from progression of disease, the therapy itself, or from other causes.
Life expectancy: of 6 months or greater
The following baseline labs must be completed within 28 days prior to registration for protocol therapy:
Hepatic:
* total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 x ULN (except subject with Gilbert's Syndrome, who can have total bilirubin \< 3.0 mg/dl)
* aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
* alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
Renal:
* Serum creatinine ≤ 3 mg/dL OR
* if serum creatinine \> 3mg/dL, estimated glomerular filtration rate (GFR) ≥ 20 mL/min
Hematopoietic:
* hemoglobin ≥ 9 g/dL, subjects requiring transfusion will not be eligible to start study
* and absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L
* and platelet count ≥ 100 × 10\^9/L
Coagulation:
* INR \< 1.5 × ULN OR
* for subjects receiving anticoagulant, the subjects must, in the investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for subjects on warfarin should be in the therapeutic range. Low molecular weight heparin (LMWH) is allowed.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: