Galinpepimut-S in Combination With Pembrolizumab in Patients With Selected Advanced Cancers

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
transplant).

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). Pembrolizumab will be administered no earlier than 30 minutes
after the administration of galinpepimut-S on Day 1 of each cycle where the 2 drugs are being
co-administered.

Inclusion Criteria:

- 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

- Has 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 will be tested for WT1 expression via IHC in both their initial primary
tumor and recent biopsy of metastatic disease at the time of screening for study
entry, or, specifically for AML, leukemic blasts either in the BM or PB.

- 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)

- Have measurable disease based on RECIST v1.1 as determined by the local study team.

- AML patients are allowed to have undergone prior chemotherapy (other than HMAs), but
should have received the last dose of their most recent chemotherapy regimen at least
28 days prior to first galinpepimut-S administration.

- 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
intervention.

- (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)≥1,500 /mcL

- Platelets ≥100,000 / mcL

- Hemoglobina ≥ 9 g/dL or ≥5.6 mmol/L,

- Renal Creatinine OR Measured or calculated creatinine clearance ≤ 1.5 ULN OR ≥ 30
mL/min for patient with creatinine levels >1.5 institutional ULN

- Total bilirubin ≤1.5 ULN OR direct bilirubin ≤ULN for patients with total
bilirubin levels >1.5ULN.

- AST (SGOT) and ALT (SGPT) ≤ 2.5ULN OR ≤ 5ULN for patients with liver metastases

- INR or PT/PTT ≤1.5 ULN unless patient is receiving anticoagulant therapy as long
as PT or PTT is within 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).

(iii). SCLC(second line)

- Histologically or cytologically confirmed SCLC based on biopsy of the tumor at initial
presentation.

- 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
status.

- 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.

(v). AML

- Pathologically or morphologically confirmed de novo or secondary AML at the time of
initial diagnosis.

- 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 shall remain on HMA therapy.

Exclusion Criteria:

- Has disease that is suitable for local therapy administered with curative intent.

- Is currently participating and 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 a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10mg daily of prednisone equivalentor a maximum dose of a
corticosteroid not to exceed 10 mg). Steroids taken as short-term therapy (≤7 days)
for antiemesis are permissible.

- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to first
study treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due
to agents administered more than 4 weeks earlier.

- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 3 months prior to first study treatment or who has not recovered (i.e., ≤ Grade
1 or at baseline) from AEs due to a previously administered agent.

Note: Patients with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this
criterion and may qualify for the study.

Note: If patient received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting study drugs.

- 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.

- Has a known additional malignancy that is progressing or requires active treatment.

- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Note: Patients with previously treated brain metastases and/or
carcinomatous meningitis may participate provided they are clinically stable for at
least 2 weeks and, have no evidence of new or enlarging brain metastases, AND are also
off steroids 3 days prior to first study treatment. Subjects with known untreated,
asymptomatic brain metastases (ie, no neurological symptoms, no requirements for
corticosteroids, no or minimal surrounding edema, and no lesion >1.5 cm) may
participate but will require regular imaging of the brain as a site of disease.

- Active autoimmune disease that has required systemic treatment in the past 2 years
(i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive
drugs) or history of an autoimmune disease that required immune suppressive therapy,
such as but not limited to inflammatory bowel disease, systemic lupus erythematosus,
ankylosing spondylitis, scleroderma, or multiple sclerosis. History of vitiligo is
permissible. Replacement therapy (e.g., thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is
not considered a form of systemic treatment.

- Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.

- Has a history of interstitial lung disease(ILD).

- Has an active infection requiring systemic therapy.

- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the patient's
participation for the full duration of the trial, or is not in the best interest of
the patient 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
treatment.

- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial or judged by the treating investigator
that such disorders could possibly lead to noncompliance with the protocol.

- A WOCBP who has a positive urine pregnancy test (e.g., within 72 hours prior to
treatment). If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required.

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of trial treatment.

- 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
irAE.

- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).

- Has known active hepatitis B (e.g., hepatitis B antigen [HBsAg] reactive) or hepatitis
C (e.g., hepatitis C virus ribonucleic acid [HCV RNA] [qualitative] is detected).

- 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 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).

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 of, or current diagnosis of CNS leukemia

2. Second line patients or patients who received any chemotherapy ("3 + 7" regimen) and
subsequently switch to HMAs are ineligible for enrollment.