| Eligibility |
Inclusion Criteria:
- 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-ß-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.
Exclusion Criteria:
- 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).
- 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.
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