Pembrolizumab + Imprime PGG for Metastatic Non-small Cell Lung Cancer After Progression on First-Line Therapy: Big Ten Cancer Research Consortium BTCRC-LUN15-017

NCT03003468 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: BTCRC-LUN15-017
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Anti-PD-1; Pembrolizumab; Imprime PGG; MK-3475

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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)

  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)

  Up to maximum of 32 months

• Progression Free Survival (PFS) at 6 Months

  6 months

• Overall Survival (OS)

  Time of treatment start until death or date of last contact, up to a maximum of 52 months.

Study Arms (1)

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.

Drug: Imprime PGG; Drug: MK-3475

Interventions

MK-3475 DRUG

200mg IV

Also known as: pembrolizumab, Keytruda

Arm A - Phase Ib

Imprime PGG DRUG

Arm A: Phase Ib Cohort 1: 2mg/kg IV; Arm A: Phase Ib Cohort 2: 4mg/kg IV

Arm A - Phase Ib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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 \[(HIV) HIV 1/2 antibodies\].
• Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• 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.

Sponsors & Collaborators

• Lawrence Feldman, MD: lead
• Merck Sharp & Dohme LLC: collaborator
• HiberCell, Inc.: collaborator

Study Sites (5)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Indiana Univeristy Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (1)

• 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.

  PMID: 39670007 DERIVED

Related Links

• Big Ten Cancer Research Consortium Website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-921-2050

Study Officials

• Lawrence Feldman, M.D.

  Big Ten Cancer Research Consortium

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: December 22, 2016
• First Posted: December 28, 2016
• Study Start: July 11, 2017
• Primary Completion: November 22, 2021
• Study Completion: November 28, 2022
• Last Updated: January 20, 2026
• Results First Posted: August 13, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)