This is a Phase 1/2, open-label, non-comparative, multicenter, multi-arm study of the Wilms
Tumor-1 (WT1)-targeting multivalent heteroclitic peptide immunotherapeutic vaccine
galinpepimut-S in combination with the programmed death-1 (PD1) inhibitor pembrolizumab in
patients with selected advanced cancers. This study will assess the efficacy and safety of
galinpepimut-S and pembrolizumab and investigate the effect of galinpepimut-S and
pembrolizumab on various tumor types. Patients will be followed long-term for OS and safety.
The study will enroll approximately 90 patients at up to 20 centers in the United States.
Indications treated are colorectal (third or fourth line), ovarian (second or third line),
small cell lung cancer (second line), breast cancer (triple negative; second line), acute
myelogenous leukemia (unable to attain deeper morphological response than partial [PR] on
hypomethylating agents and who are not eligible for allogeneic hematopoietic stem cell
The first 2 galinpepimut-S injections will initially be administered as monotherapy every 3
weeks (Week 0 and Week 3). Thereafter, galinpepimut-S will be co-administered with
pembrolizumab every 3 weeks for 4 additional administrations (for the galinpepimut-S initial
immunization induction phase series; weeks 6-15) to coincide with the per label pembrolizumab
dosing frequency. After that, there will be one un-paired administration of pembrolizumab
(week 18), and then galinpepimut-S will be resumed on an every 3-week schedule for 6
additional doses (early immune booster phase; weeks 21-36). At the end of this phase, there
will be a 12-week interval where 3 unpaired administrations of pembrolizumab will occur
(weeks 39-45), and then galinpepimut-S will be resumed on an every 12-week schedule for 4
additional doses (late immune booster phase; weeks 48-84). After 84 weeks, continuing
non-progressed patients will be treated with pembrolizumab alone up until week 111.
Pembrolizumab will be administered at a dose of 200 mg intravenously every 3 weeks on Day 1
of each cycle (3 week cycles) starting on Study Week 6 and continuing for up to 2 years
thereafter (Study Week 111). Galinpepimut-S will be administered 30-60 minutes after the
completion of IV infusion of pembrolizumab on Day 1 of each cycle during which the 2 drugs
are being co-administered.
- Is willing and able to understand and provide signed informed consent for the study
that fulfills IRB guidelines
- Male or female patients >18 years of age on the day of signing informed consent
- Histologically or cytologically-confirmed advanced or metastatic solid tumors who have
disease progression after treatment with available therapies for metastatic disease
that are known to confer clinical benefit, or are intolerant to treatment, or refuse
standard treatment in the context of the particular line of treatment or, specifically
for AML, demonstrate as their best response after 4 cycles of HMA therapy the status
of "partial response" per European LeukemiaNet (ELN) criteria and meet the additional
specified requirements for the cohort of the study they will enroll into.
- All patients in the solid tumor arms will be tested for WT1 expression via IHC in
their initial primary tumor OR recent biopsy of metastatic disease at the time of
screening for study entry. Specifically for AML, patients will be tested for WT1
expression via IHC in their leukemic blasts either in the BM or PB. Assessment of WT1
expression positivity will be performed via central review prior to study entry.
- Patients may have received a specific maximum allowable number of prior lines of
therapy for metastatic disease, as follows: CRC: 2 or 3 lines; OvC: 1 or 2 lines;
SCLC: 1 line; TNBC: 1 line; and AML: 1 line (allo-SCT-eligible status not allowed)
- For solid tumor arms: patients must measurable disease based on RECIST v1.1 as
determined by the local study team.
- For AML arm, eligibility is defined as:
1. Prior frontline (1st line) with HMAs since initial AML diagnosis;
2. Prior cytoreductive therapy with hydroxyurea or leukapheresis at the time of
initial diagnosis, with subsequent immediate seamless transitioning to HMA
3. History of induction early failure after initial therapy with up to 2 cycles of
standard chemotherapy ("7+3" or similar regimen), with subsequent immediate
seamless transitioning to HMA therapy as long as patients have achieved PR as
their best observable response after 4 cycles of HMA therapy; HMA therapy
continues throughout the trial period.
- Resolution of toxicity effect(s) from most recent prior chemotherapy to Grade 1 or
less (except alopecia). If the patient received major surgery or radiation therapy of
> 30 Gy, they must have recovered from the toxicity and/or complications from the
- (ECOG) performance status of 0 or 1.
- For women of child-bearing potential, agreement to use adequate birth control
(abstinence, hysterectomy, bilateral oophorectomy, bilateral tubal ligation, oral
contraception, IUD, or use of condoms or diaphragms)
- Male patients of childbearing potential must agree to use an adequate method of
contraception, starting with the first dose of study therapy through 4 months
following the last study treatment.
- Have adequate organ function as defined:
- Absolute neutrophil count (ANC) ≥1500/µL
- Platelets ≥100,000/µL
- Hemoglobin (Hb) ≥9.0 g/dL or ≥5.6 mmol/L (N.B.: Hb criterion must be met without
erythropoietin dependency and without packed red blood cell transfusion within
last 2 weeks)
- Creatinine ≤1.5 × upper limit of normal (ULN) OR Measured or calculated
creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥30
mL/min for subjects with creatinine levels >1.5 × institutional ULN
- Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for subjects with total
bilirubin levels >1.5 × ULN
- AST (SGOT) and ALT (SGPT) ≤2.5 × ULN OR ≤5 × ULN for subjects with liver
- International normalized ratio (INR) OR prothrombin time (PT) and Activated
partial thromboplastin time (aPTT) ≤1.5 × ULN, unless subjects are receiving
anticoagulant therapy as long as PT or aPTT is within the therapeutic range of
intended use of anticoagulants
Additional Inclusion Criteria for Selected Tumor Types:
(i).Colorectal Cancer (third/fourth line)
- Histologically or cytologically documented adenocarcinoma of colon or rectum at the
time of initial presentation.
- Metastatic CRC with documented disease progression (per standard criteria) after the
last administration of standard therapies or intolerance to standard therapies (and
approved therapies must have included all the following a fluoropyrimidine,
oxaliplatin, irinotecan, bevacizumab, and, if KRAS wild-type, cetuximab or
panitumumab). Prior use of and failure after regorafenib or trifluridine/tipiracil is
allowed but not mandated.
(ii). OvC (second/third line)
- Histologically diagnosed ovarian, fallopian tube or primary peritoneal cancer at the
time of initial presentation.
- Patients will have either relapsed or be disease resistant to their prior therapy.
Interval surgery is permitted, but patients must have objective evidence of disease on
computed tomography (CT)or magnetic resonance imaging (MRI), with concomitant CA-125
increase and/or biopsy showing OvC (only for recurrent disease).
- Patients should have received platinum-containing chemotherapy and been designated as
harboring platinum-refractory or -resistant disease. Additionally, all eligible
subjects should have either received (or been offered) bevacizumab therapy, and those
with BRCA germline mutations (gBRCA mut) should have been offered therapy with
poly-ADP ribose polymerase (PARP) inhibitors (olaparib, rucaparib or niraparib).
(iii). SCLC (second line)
- Histologically or cytologically confirmed SCLC based on biopsy of the tumor at initial
- Asymptomatic or treated brain metastases are allowed.
- Patients must have measurable disease (by CT or MRI) after they progressed or were
resistant to 1 prior systemic therapy.
(iv). TNBC (second line)
- Histologically proven metastatic breast carcinoma with triple negative receptor
- TNBC status is defined as estrogen and progesterone receptor negative by IHC, and
human epidermal growth factor receptor 2 [HER2] negative by IHC AND HER2 gene
non-amplified by fluorescence in situ hybridization [FISH], per standard criteria.
Patients who are weakly positive for the estrogen or progesterone receptor (i.e., <
5%) are eligible.
- Patients must have measurable disease(by CT or MRI) after they progressed or were
resistant to 1 prior systemic therapy.
- Patients have undergone second-line therapy after residual or recurrent disease after
first-line therapy. The latter may have included:
1. Neoadjuvant therapy if macroscopic disease was still present after surgery OR
2. Adjuvant therapy, but only if the macroscopic relapse occurred > 6 months from
the start of study treatment with pembrolizumab.
- Pathologically or morphologically confirmed de novo or secondary AML at the time of
- Achievement of no better than morphologic PR, as defined initially by the AML Working
Group criteria (Cheson et al,2003), and also quoted in the more recent ELN criteria
(Döhner et al, 2010),while on active treatment with HMAs.
- AML patients are eligible only if they received first-line therapy with HMAs
(decitabine or azacytidine) for 4 cycles and achieved only PR at the end of cycle 4.
- AML patients must remain on HMA therapy throughout the trial.
- Presence of disease that is suitable for local or regional therapy administered with
- Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks prior to treatment.
- N.B.: Participants must have recovered from all AEs due to previous therapies to
≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
- N.B.: If the subject underwent major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
- Has received prior radiotherapy within 2 weeks of the start of study treatment.
Subjects must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or
higher immune-related adverse event (irAE).
- Subject currently participates in a clinical trial with another investigational agent
and is 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 study treatment.
- Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
are generally killed virus vaccines and are allowed; however, intranasal influenza
vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
- Has undergone prior allogeneic hematopoietic stem cell transplantation.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study drug. The use of
physiologic doses of corticosteroids may be approved after consultation with the
Sponsor. Steroids taken as short-term therapy (≤ 7 days) for antiemesis are
- Has a known additional malignancy that is progressing or has required active treatment
within the past 5 years, even if currently inactive or unapparent.
- N.B.: Specifically, AML patients with prior history of myelodysplastic syndromes or
myeloproliferative neoplasms are not excluded. Participants in any of the study arms
(solid tumors or AML) with basal cell carcinoma of the skin, squamous cell carcinoma
of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ)
that have undergone potentially curative therapy, as well as patients with prostate
cancer managed clinically with "watchful waiting" are eligible.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study treatment.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Has known hypersensitivity to Montanide or vaccine adjuvants.
- Had a previous clinically significant systemic allergic reaction to Montanide,
sargramostim (GM-CSF), or filgrastim (G-CSF).
- Has an active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a form
of systemic treatment and is allowed.
- Has a history of (non-infectious) pneumonitis that required steroids or has current
- Has an active infection requiring systemic therapy.
- Subjects with known human immunodeficiency virus (HIV) and/or history of Hepatitis B
or C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B
virus (HBV) DNA or Hepatitis C Antibody or RNA are excluded. Active Hepatitis C is
defined by a known positive Hep C Ab result and known quantitative HCV RNA results
greater than the lower limits of detection of the assay.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the patient's
participation for the full duration of the study, or is not in the best interest of
the participant to participate, in the opinion of the treating investigator. This
includes any serious, intercurrent, chronic, or acute illness, such as cardiac disease
(New York Heart Association [NYHA] class III or IV), hepatic disease, or other illness
considered by the investigator as an unwarranted high risk for investigational drug
- Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.
- For female subjects: Subject is pregnant or breastfeeding or expecting to conceive or
father children within the projected duration of the study, starting with the
screening visit through 30 days after the last dose of study treatment.
- Has had an allogeneic tissue/solid organ transplant.
- Has received transfusion of blood products (including platelets or red blood cells) or
administration of colony stimulating factors (excluding GM-CSF, but including G-CSF or
recombinant erythropoietin) within 4 weeks prior to first study treatment.
Additional Exclusion Criteria for Selected Tumor Types:
(i). CRC: None (ii). OvC: None (iii). SCLC: Mixed SCLC (iv). TNBC: None (v). AML:
1. Planned/anticipated HSCT (autologous or allogeneic, with any degree of match donor);
acute promyelocytic leukemia (APL; M3 or any morphologic and molecular variants,
inclusive); history or current diagnosis of CNS leukemia
2. Relapsed (Second line) patients
- N.B.: Patients who received any chemotherapy ("3 + 7" or similar chemotherapy
regimen) for up to 2 cycles during initial induction therapy in the first-line
setting and subsequently immediately seamlessly switched to HMAs are eligible.