Non-Small Cell Lung CancerPhase 1/2NCT03003468
Pembrolizumab + Imprime PGG for Metastatic Non-small Cell Lung Cancer After Progression on First-Line Therapy: Big Ten Cancer Research Consortium BTCRC-LUN15-017
A Phase 1/2 study testing Imprime PGG and MK-3475 in people with Non-Small Cell Lung Cancer, run by Lawrence Feldman, MD at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Imprime PGG and MK-3475
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 5 sitesUnited States
- Study dates
- 11 Jul 2017to 28 Nov 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥ 18 years of age at time of consent.
- Subjects with histologically or cytologically confirmed non-small cell lung cancer (NCSLC).
- Subjects with stage IV non-small cell lung cancer as defined by American Joint Committee on Cancer (AJCC).
- Phase Ib: Subjects who progressed after first-line platinum-based chemotherapy and who are candidates for second-line therapy.
- Phase II: Subjects who have progressed on first-line systemic therapy (either platinum-based chemotherapy with or without immune checkpoint inhibitor or immune checkpoint inhibitor as first line therapy) who are candidates for second-line systemic therapy. Patients with early stage cancer will also be eligible if progression occurs:
- within 6 months of adjuvant chemotherapy after curative resection
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- within 6 months of adjuvant chemotherapy after curative resection while on adjuvant immunotherapy, currently only available as part of a clinical trial
- within 6 months of curative surgery if chemotherapy is given in the neoadjuvant setting
- within 6 months of completion of chemoradiation (or 6 months from completion of consolidation chemotherapy if administered after concurrent chemoradiation)
- within 6 months of completion of chemoradiation or consolidation chemotherapy (if administered) while on consolidation immunotherapy, a setting for which durvalumab is FDA approved.
- Phase II: Subjects with an EGFR or ALK mutation who are no longer candidates for TKI therapy and have progressed on standard systemic therapy (either platinum-based chemotherapy with or without immune checkpoint inhibitor or immune checkpoint inhibitor as first line therapy).
- Phase II only: Measurable disease according to RECIST v1.1 (Section 8) obtained by imaging within 28 days prior to study registration. Phase Ib: subjects may enroll with or without measurable disease.
- Phase II only: Subjects must have presence of peripheral blood levels of IgG anti-β-glucan antibody (ABA) of ≥ 20 μg/mL as determined by an ELISA test within 90 days prior to study registration.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 within 28 days prior to study registration.
- Life expectancy of 6 months or greater as determined by the treating physician.
- Adequate hepatic function within 28 days prior to study registration defined as meeting all of the following criteria:
- 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
- Adequate renal function within 28 days prior to study registration defined by either of the following criteria:
- Serum creatinine ≤ 3 mg/dL
- if serum creatinine > 3mg/dL, estimated glomerular filtration rate (GFR) ≥ 20 mL/min
- Adequate hematologic function within 28 days prior to study registration defined as meeting all of the following criteria:
- hemoglobin ≥ 9 g/dL; subjects requiring transfusion will be eligible to start study
- and absolute neutrophil count (ANC) ≥ 1.5 × 109/L
- and platelet count ≥ 100 × 109/L
- Adequate coagulation functioning within 28 days prior to study registration defined by either of the following criteria:
- INR < 1.5 × ULN
- 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.
- Provided written informed consent and HIPAA authorization for release of personal health information, approved by an Institutional Review Board (IRB). NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- Women of childbearing potential (WOCP) must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required within 72 hours of study registration. If the urine test cannot be confirmed as negative, a serum pregnancy test will be required.
- Women of childbearing potential (WOCP) must be willing to use two effective methods of birth control such as an oral, implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total abstinence for the course of the study until 120 days after the last dose of study drug. NOTE: Women are considered to be of childbearing potential unless they are postmenopausal (≥45 years of age and has not had menses for greater than 12 consecutive months), surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or not heterosexually active for the duration of the study and at least 120 days after the last dose of study drug.
- Men who are not surgically sterile (vasectomy) must agree to use an acceptable method of contraception. Male subjects with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms from the first dose of study drug through at least 120 days after the last dose of study drug. Total abstinence for the same study period is an acceptable alternative.
- Willingness and ability to comply with scheduled visits (including geographical distance), treatment plans, laboratory tests, and other study procedures.
Who cannot join
- Surgery within 4 weeks prior to study registration except for minor procedures. NOTE: Hepatic biliary stent placement, PleurX catheter, port replacement, ureteral stent or other minor surgeries are allowed. NOTE: Subject must have adequately recovered from the toxicity and/or complications of major surgery prior to study registration, as determined by the treating physician.
- Patients with known untreated or active central nervous system (CNS) metastases. Subjects suspected to have brain mets should undergo brain MRI (or CT head if MRI is not feasible) to exclude brain metastases. Patients with treated brain metastases will be eligible as long as their symptoms are improving or achieved new baseline and not requiring steroids for at least 2 weeks. Patients with leptomeningeal disease will be excluded regardless of clinical stability.
- Previously received a solid organ transplant or allogeneic progenitor/stem cell transplant.
- Received a live vaccine within 30 days prior to the first dose of trial treatment. Examples of live vaccines include, but are not limited to: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines and are not allowed.
- History of blood clots, pulmonary embolism, or deep vein thrombosis unless on adequate anticoagulant therapy as determined by the treating investigator (subject must be on stable dose for 2 weeks) and all symptoms have resolved.
- Known history of human immunodeficiency virus [(HIV) HIV 1/2 antibodies].
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- Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Current use of immunosuppressive medication at time of study entry. The following are exceptions to this exclusion criterion: intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection); steroids as premedication for hypersensitivity reactions (eg, CT scan premedication). Cases requiring systemic corticosteroids at physiologic doses must be discussed with Big Ten CRC and HiberCell prior to enrollment.
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Exceptions include: patients with controlled diabetes type 1, controlled hypo- or hyperthyroidism, resolved childhood asthma/atopy, vitiligo, or psoriasis not requiring immunosuppressive treatment.
- Received prior chemotherapy, an immune checkpoint inhibitor, or radiation therapy within 2 weeks prior to study registration or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events from previously administered agents. NOTE: Subjects with alopecia, grade ≤ 2 sensory neuropathy or other grade ≤ 2 AEs not constituting a safety risk based on investigator judgement are an exception to this criterion and can still be considered for the study.
- Any clinically significant infection requiring anti-infective treatment. Patients with infection that is adequately treated will be eligible.
- History of interstitial lung disease requiring immunosuppressive/steroids or history of immunotherapy related pneumonitis that has required steroids or immunosuppression in the past.
- Known history of active tuberculosis.
- Any other severe, uncontrolled medical condition, including uncontrolled diabetes mellitus (defined as a Hemoglobin A1C ≥ 9% in subjects with a prior history of diabetes, 28 days prior to study registration) or unstable congestive heart failure (Stage III-IV of the New York Heart Association Functional Classification).
- Previous known allergy or intolerance to pembrolizumab or any of its excipients.
- Previous exposure or known allergy to Imprime PGG or any of its excipients.
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, interfere with protocol compliance, or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for enrollment in this study.
- Presence of any non-healing wound, fracture, or ulcer within 28 days prior to study registration.
- Any mental or medical condition that prevents the subject from giving informed consent or participating in the trial.
- No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, Gleason ≤ grade 7 prostate cancers, low grade papillary urothelial carcinoma or other cancer for which the subject has been disease-free for at least 2 years. And no additional therapy other than hormonal therapy is required for anticipated to be required during the trial period.
- Treatment with any therapeutic investigational agent within 28 days prior to study registration.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Illinois at Chicago
Chicago, Illinois, 60612
Penn State Cancer Institute
Hershey, Pennsylvania, 17033
Indiana Univeristy Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
University of Iowa Hospital and Clinics
Iowa City, Iowa, 52242
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
About this study
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
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.
Read the 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.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Imprime PGG, MK-3475
- Keywords
- Anti-PD-1, Pembrolizumab, Imprime PGG, MK-3475
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imprime PGGDrug
Arm A: Phase Ib Cohort 1: 2mg/kg IV; Arm A: Phase Ib Cohort 2: 4mg/kg IV
MK-3475Drug
Also called pembrolizumab, Keytruda
200mg IV
Imprime PGGDrug
Arm B: Phase II treatment: administered at the maximum safe dose of 2mg or 4 mg as established in the Phase Ib cohort study.
| Study group | Role | What they receive |
|---|---|---|
| Arm A - Phase Ib | Experimental | Dose Escalation Cohort Cohort 1 will consist of 3-6 patients who will receive pembrolizumab 200mg IV on Day 1 of each 21 day cycle. Imprime PGG will be administered at 2mg/kg on Day 1,8, and 15 of cycles 1-4, and on Day 1 of cycles 5-16. On Day 1 of each cycle, the Imprime PGG intravenous infusion is given first followed 15-30 minutes later by the pembrolizumab.
Experimental: Arm A - Phase II Investigational Treatment The maximum safe dose of Imprime PGG in combination with pembrolizumab (as determined in the phase Ib cohort) will be given on Day 1,8, and 15 for cycles 1-4, and on Day 1 of cycles 5-16.
Cohort 2 will consist of 3-6 patients who will receive pembrolizumab 200mg IV on Day 1 and Imprime PGG at 4mg/kg on Day 1,8, and 15 for Cycles 1-4 and on Day 1 only for Cycles 5-16. On Day 1 of each cycle, the Imprime PGG intravenous infusion is given first followed 15-30 minutes later by the pembrolizumab. Receives: Drug: Imprime PGG; Drug: MK-3475 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib: Maximum Tolerated Dose
Phase Ib: Maximum tolerated dose (MTD) for subjects receiving Imprime PGG with pembrolizumab without experiencing dose-limiting toxicity(s) (DLT) per Common Terminology Criteria for Adverse Events (CTCAE) v4.
Measured: 21 days
Progression Free Survival
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Progression Free Survival (PFS) is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause.
Measured: Time of treatment start until the criteria for disease progression or death. Up to a maximum of 32 months.
Secondary outcomes (4)
Adverse Events (AEs)
Number of participants with treatment related adverse events regardless of dose are reported by CTCAEv4 term and grade.
Measured: AEs have been recorded from the time of consent until 30 days after treatment discontinuation of study drugs or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 13 months
Clinical Benefit Rate (CBR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD.The CBR is defined as the proportion of subjects with a confirmed complete response, partial response or stable disease based on RECIST v1.1.
Measured: Up to maximum of 32 months
Progression Free Survival (PFS) at 6 Months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause.
PFS at 6 months is defined as the percentage of patient who was progression free at 6 months from the initiation of treatment.
Measured: 6 months
Overall Survival (OS)
Overall survival is defined as the time from treatment start until death or date of last contact.
Measured: Time of treatment start until death or date of last contact, up to a maximum of 52 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2016 (estimated)
- Study start11 Jul 2017
- Primary completion22 Nov 2021
- Study completion28 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lawrence Feldman, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, HiberCell, Inc.
- Responsible party
- Sponsor-investigator, Lawrence Feldman, MD, Big Ten Cancer Research Consortium
- Investigators
- Lawrence Feldman, M.D., Study chair, Big Ten Cancer Research Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03003468
- Sponsor's protocol ID
- BTCRC-LUN15-017
- Status last verified
- Dec 2025
- First submitted
- 22 Dec 2016
- Last updated
- 20 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Furqan M, Malhotra J, Shergill A, Liu L, Mott SL, Pasquinelli MM, Hulbert A, Kennedy K, Feldman L. Phase Ib/II study of imprime PGG and pembrolizumab in patients with previously treated advanced non-small cell lung cancer (NSCLC): BTCRC LUN 15-017. Transl Lung Cancer Res. 2024 Nov 30;13(11):2998-3009. doi: 10.21037/tlcr-24-346. Epub 2024 Nov 19.
PubMed 39670007
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03003468
- Acronym / sponsor ID
- BTCRC-LUN15-017
- Conditions
- Non-Small Cell Lung Cancer
- Keywords
- Anti-PD-1, Pembrolizumab, Imprime PGG, MK-3475
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Lawrence Feldman, MDUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, HiberCell, Inc.
- Study start
- 11 Jul 2017 (actual)
- Primary completion
- 22 Nov 2021 (actual)
- Study completion
- 28 Nov 2022 (actual)
- First posted
- 28 Dec 2016 (estimated)
- Results
- Posted 13 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm A - Phase Ib | Experimental | Drug: Imprime PGG, Drug: MK-3475Dose Escalation Cohort Cohort 1 will consist of 3-6 patients who will receive pembrolizumab 200mg IV on Day 1 of each 21 day cycle. Imprime PGG will be administered at 2mg/kg on Day 1,8, and 15 of cycles 1-4, and on Day 1 of cycles 5-16. On Day 1 of each cycle, the Imprime PGG intravenous infusion is given first followed 15-30 minutes later by the pembrolizumab. Experimental: Arm A - Phase II Investigational Treatment The maximum safe dose of Imprime PGG in combination with pembrolizumab (as determined in the phase Ib cohort) will be given on Day 1,8, and 15 for cycles 1-4, and on Day 1 of cycles 5-16. Cohort 2 will consist of 3-6 patients who will receive pembrolizumab 200mg IV on Day 1 and Imprime PGG at 4mg/kg on Day 1,8, and 15 for Cycles 1-4 and on Day 1 only for Cycles 5-16. On Day 1 of each cycle, the Imprime PGG intravenous infusion is given first followed 15-30 minutes later by the pembrolizumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- Male or female ≥ 18 years of age at time of consent.
- Subjects with histologically or cytologically confirmed non-small cell lung cancer (NCSLC).
- Subjects with stage IV non-small cell lung cancer as defined by American Joint Committee on Cancer (AJCC).
- Phase Ib: Subjects who progressed after first-line platinum-based chemotherapy and who are candidates for second-line therapy.
- Phase II: Subjects who have progressed on first-line systemic therapy (either platinum-based chemotherapy with or without immune checkpoint inhibitor or immune checkpoint inhibitor as first line therapy) who are candidates for second-line systemic therapy. Patients with early stage cancer will also be eligible if progression occurs:
Key exclusion criteria (22 listed)
- Surgery within 4 weeks prior to study registration except for minor procedures. NOTE: Hepatic biliary stent placement, PleurX catheter, port replacement, ureteral stent or other minor surgeries are allowed. NOTE: Subject must have adequately recovered from the toxicity and/or complications of major surgery prior to study registration, as determined by the treating physician.
- Patients with known untreated or active central nervous system (CNS) metastases. Subjects suspected to have brain mets should undergo brain MRI (or CT head if MRI is not feasible) to exclude brain metastases. Patients with treated brain metastases will be eligible as long as their symptoms are improving or achieved new baseline and not requiring steroids for at least 2 weeks. Patients with leptomeningeal disease will be excluded regardless of clinical stability.
- Previously received a solid organ transplant or allogeneic progenitor/stem cell transplant.
- Received a live vaccine within 30 days prior to the first dose of trial treatment. Examples of live vaccines include, but are not limited to: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines and are not allowed.
- History of blood clots, pulmonary embolism, or deep vein thrombosis unless on adequate anticoagulant therapy as determined by the treating investigator (subject must be on stable dose for 2 weeks) and all symptoms have resolved.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imprime PGGArm A: Phase Ib Cohort 1: 2mg/kg IV; Arm A: Phase Ib Cohort 2: 4mg/kg IV | Drug | Arm A - Phase Ib |
| MK-3475Also: pembrolizumab, Keytruda200mg IV | Drug | Arm A - Phase Ib |
| Imprime PGGArm B: Phase II treatment: administered at the maximum safe dose of 2mg or 4 mg as established in the Phase Ib cohort study. | Drug | Arm A - Phase Ib |
Primary outcome
Phase Ib: Maximum Tolerated Dose
Time frame: 21 days
Phase Ib: Maximum tolerated dose (MTD) for subjects receiving Imprime PGG with pembrolizumab without experiencing dose-limiting toxicity(s) (DLT) per Common Terminology Criteria for Adverse Events (CTCAE) v4.
Progression Free Survival
Time frame: Time of treatment start until the criteria for disease progression or death. Up to a maximum of 32 months.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Progression Free Survival (PFS) is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause.
4 secondary outcomes
Adverse Events (AEs)
Time frame: AEs have been recorded from the time of consent until 30 days after treatment discontinuation of study drugs or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 13 months
Clinical Benefit Rate (CBR)
Time frame: Up to maximum of 32 months
Progression Free Survival (PFS) at 6 Months
Time frame: 6 months
Overall Survival (OS)
Time frame: Time of treatment start until death or date of last contact, up to a maximum of 52 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39670007Furqan M, Malhotra J, Shergill A, Liu L, Mott SL, Pasquinelli MM, Hulbert A, Kennedy K, Feldman L. Phase Ib/II study of imprime PGG and pembrolizumab in patients with previously treated advanced non-small cell lung cancer (NSCLC): BTCRC LUN 15-017. Transl Lung Cancer Res. 2024 Nov 30;13(11):2998-3009. doi: 10.21037/tlcr-24-346. Epub 2024 Nov 19.
- Big Ten Cancer Research Consortium WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lawrence Feldman, M.D. study chair
Big Ten Cancer Research Consortium
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Imprime PGG and MK-3475 in people with Non-Small Cell Lung Cancer, run by Lawrence Feldman, MD at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib: Maximum Tolerated Dose (time frame: 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03003468, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026.